CoviRx

Covid19 Drug Repurposing Database

List of References:

1 Probst, Daniel, Reymond, Jean-Louis. SmilesDrawer: Parsing and Drawing SMILES-Encoded Molecular Structures Using Client-Side JavaScript. J. Chem. Inf. Model. 2018, 58, 1, 1–7
2 Therapeutic Goods Administration (TGA). 2022. Search the TGA website. [online] Available at: <https://tga-search.clients.funnelback.com/s/search.html?query=&collection=tga-artg> [Accessed 20 January 2022].
3 Accessdata.fda.gov. 2022. Drugs@FDA: FDA-Approved Drugs. [online] Available at: <https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm> [Accessed 20 January 2022].
4 Drugs.ncats.io. 2022. NCATS Inxight Drugs. [online] Available at: <https://drugs.ncats.io/> [Accessed 20 January 2022].
5 Balakrishnan R, et al. Isolongifolene attenuates rotenone-induced mitochondrial dysfunction, oxidative stress and apoptosis. Front Biosci (Schol Ed). 2018 Jan 1;10:248-261.
6 https://clinicaltrials.gov/ct2/show/NCT04445623?term=Prasugrel&cond=COVID-19&draw=2&rank=1 https://clinicaltrials.gov/ct2/show/NCT04505774?term=Prasugrel&cond=COVID-19&draw=2&rank=2 https://clinicaltrials.gov/ct2/show/NCT02735707?term=Prasugrel&cond=COVID-19&draw=2&rank=3 https://clinicaltrials.gov/ct2/show/NCT04518735?term=Prasugrel&cond=COVID-19&draw=2&rank=4
7 Wang W, et al. RIP1 Kinase Drives Macrophage-Mediated Adaptive Immune Tolerance in Pancreatic Cancer. Cancer Cell. 2018 Nov 12;34(5):757-774.e7.
8 Masuda M, et al. Activating transcription factor 4 regulates stearate-induced vascular calcification. J Lipid Res. 2012 Aug;53(8):1543-52.
9 Liu G, et al. Discovery of potent, selective, orally bioavailable stearoyl-CoA desaturase 1 inhibitors. J Med Chem. 2007 Jun 28;50(13):3086-100.
10 Koeberle A, et al. Palmitoleate is a mitogen, formed upon stimulation with growth factors, and converted to palmitoleoyl-phosphatidylinositol. J Biol Chem. 2012 Aug 3;287(32):27244-54.
11 Kamphorst JJ, et al. Hypoxic and Ras-transformed cells support growth by scavenging unsaturated fatty acids from lysophospholipids. Proc Natl Acad Sci U S A. 2013 May 28;110(22):8882-7.
12 H Hidaka, et al. N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, a Calmodulin Antagonist, Inhibits Cell Proliferation. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4354-7.
13 M Asano. Divergent Pharmacological Effects of Three Calmodulin Antagonists, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), Chlorpromazine and Calmidazolium, on Isometric Tension Development and Myosin Light Chain Phosphorylation in Intact Bovine Tracheal Smooth Muscle. J Pharmacol Exp Ther. 1989 Nov;251(2):764-73.
14 H Itoh, et al. Direct Interaction of Calmodulin Antagonists With Ca2+/calmodulin-dependent Cyclic Nucleotide Phosphodiesterase. J Biochem. 1984 Dec;96(6):1721-6.
15 Shigeyuki Yokokura, et al. Calmodulin Antagonists Induce Cell Cycle Arrest and Apoptosis in Vitro and Inhibit Tumor Growth in Vivo in Human Multiple Myeloma. BMC Cancer. 2014 Nov 26;14:882.
16 Kim H, et al. Sulfiredoxin inhibitor induces preferential death of cancer cells through reactive oxygen species-mediated mitochondrial damage. Free Radic Biol Med. 2016 Feb;91:264-74.
17 Ueno S, et al. Bicuculline and gabazine are allosteric inhibitors of channel opening of the GABAA receptor. J Neurosci. 1997 Jan 15;17(2):625-34.
18 Drug Metab Dispos 8:1284 (2000); Ned Tijdschr Geneeskd.151:1945 (2007)
19 Tridib Mondal, et al. ApoE: In Vitro Studies of a Small Molecule Effector. Biochemistry. 2016 May 10;55(18):2613-21.
20 Noguchi K, et al. Fibrinolytic potential of DS-1040, a novel orally available inhibitor of activated thrombin-activatable fibrinolysis inhibitor (TAFIa). Thromb Res. 2018 Aug;168:96-101.
21 Hothersall JD, et al. Sustained wash-resistant receptor activation responses of GPR119 agonists. Eur J Pharmacol. 2015 Sep 5;762:430-42.
22 Lan H, et al. Agonists at GPR119 mediate secretion of GLP-1 from mouse enteroendocrine cells through glucose-independent pathways. Br J Pharmacol. 2012 Apr;165(8):2799-807.
23 Yang JW, et al. GPR119: a promising target for nonalcoholic fatty liver disease. FASEB J. 2016 Jan;30(1):324-35.
24 Miller CP, et al. Design, Synthesis, and Preclinical Characterization of the Selective Androgen Receptor Modulator (SARM) RAD140. ACS Med Chem Lett. 2010 Dec 2;2(2):124-129.
25 Jayaraman A, et al. Selective androgen receptor modulator RAD140 is neuroprotective in cultured neurons and kainate-lesioned male rats. Endocrinology. 2014 Apr;155(4):1398-1406.
26 Solt LA, et al. Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. Nature. 2012 Mar 29;485(7396):62-8.
27 Wang Y, et al. Anti-proliferative actions of a synthetic REV-ERBα/β agonist in breast cancer cells. Biochem Pharmacol. 2015 Aug 15;96(4):315-22.
28 Wu MP, et al. Higenamine protects ischemia/reperfusion induced cardiac injury and myocyte apoptosis through activation of β2-AR/PI3K/AKT signaling pathway. Pharmacol Res. 2016 Feb;104:115-23.
29 Lee SR, et al. Acute oral intake of a higenamine-based dietary supplement increases circulating free fatty acidsand energy expenditure in human subjects. Lipids Health Dis. 2013 Oct 21;12:148.
30 https://clinicaltrials.gov/ct2/show/NCT04935476?term=DAPSONE&cond=covid&draw=2&rank=1
31 Am J Opthalmol 126:400 (1998)|
32 DeSantis, L., Preclinical overview of brinzolamide. Surv Ophthalmol, 2000. 44 Suppl 2: p. S119-29.
33 Silver, L.H., Dose-response evaluation of the ocular hypotensive effect of brinzolamide ophthalmic suspension (Azopt). Brinzolamide Dose-Response Study Group. Surv Ophthalmol, 2000. 44 Suppl 2: p. S147-53.
34 Ertongur S et al. Inhibition of the invasion capacity of carcinoma cells by WX-UK1, a novel synthetic inhibitor of the urokinase-type plasminogen activator system. Int J Cancer. 2004 Jul 20;110(6):815-24.
35 Ewa Zeslawska et al. Crystals of the urokinase type plasminogen activator variant βc-uPA in complex with small molecule inhibitors open the way towards structure-based drug design. J Mol Biol. 2000 Aug 11;301(2):465-75.
36 Nicholson B, et al. Characterization of ubiquitin and ubiquitin-like-protein isopeptidase activities. Protein Sci. 2008 Jun;17(6):1035-43.
37 https://clinicaltrials.gov/ct2/show/NCT04588441?term=ADENOSINE&cond=covid&draw=2&rank=1
38 https://clinicaltrials.gov/ct2/show/NCT04467931?term=FELODIPINE&cond=covid&draw=2&rank=2
39 Chem Pharm Bull 25:2300 (1977); Phytochemistry 32:1083 (1993)
40 Koechling W, et al. A novel GnRH antagonist, causes minimal histamine release compared with abarelix in an ex vivo model of human skin samples. Br J Clin Pharmacol. 2010 Oct;70(4):580-7.
41 Guo H, et al. Peiminine ameliorates bleomycin-induced acute lung injury in rats. Mol Med Rep. 2013 Apr;7(4):1103-10.
42 Dugasani S, et al. Comparative antioxidant and anti-inflammatory effects of
43 -gingerol,
44 -gingerol, [10]-gingerol and
45 -shogaol. J Ethnopharmacol. 2010 Feb 3;127(2):515-20.
46 Almada da Silva J, et al. Purification and differential biological effects of ginger-derived substances on normal and tumor cell lines. J Chromatogr B Analyt Technol Biomed Life Sci. 2012 Aug 15;903:157-62.
47 J Int Med Res 10:160 (1982); Neuropsychobiology 14:17 (1985); Br J Psychiatry 150:164 (1987)
48 Stafford WC, et al. Irreversible inhibition of cytosolic thioredoxin reductase 1 as a mechanistic basis for anticancer therapy. Sci Transl Med. 2018 Feb 14;10(428). pii: eaaf7444.
49 Kuo CC, et al. Use-dependent inhibition of the N-methyl-D-aspartate currents by felbamate: a gating modifier with selective binding to the desensitized channels. Mol Pharmacol. 2004 Feb;65(2):370-80.
50 Harty TP, et al. Felbamate block of recombinant N-methyl-D-aspartate receptors: selectivity for the NR2B subunit. Epilepsy Res. 2000 Mar;39(1):47-55.
51 J Org Chem 50:2011 (1985)
52 Riendeau D, et al. Evaluation of loxoprofen and its alcohol metabolites for potency and selectivity of inhibition of cyclooxygenase-2. Bioorg Med Chem Lett. 2004;14(5):1201-1203.
53 Paudel S, et al. Assessing Drug Interaction and Pharmacokinetics of Loxoprofen in Mice Treated with CYP3A Modulators. Pharmaceutics. 2019;11(9):479. Published 2019 Sep 16. |Biochem. Pharmacol. (1991), 42(12), 2363-8; Biochem. Pharmacol. (1984), 33(15), 2473-8; J. Med. Chem. (1984), 27(2), 212-6
54 Touré BB, et al. Toward the Validation of Maternal Embryonic Leucine Zipper Kinase: Discovery, Optimization of Highly Potent and Selective Inhibitors, and Preliminary Biology Insight. J Med Chem. 2016 May 26;59(10):4711-23.
55 Illana Gozes, et al. Novel compounds and methods for inhibiting cell death. US 20150141345 A1.
56 Severin G. Comprehensive high-performance liquid chromatographic methodology for the determination of thiothixene in bulk drug, finished product, and dissolution testing samples. J Pharm Sci. 1987 Mar;76(3):231-4.
57 Bodenstine TM, et al. Homotypic gap junctional communication associated with metastasis suppression increases with PKA activity and is unaffected by PI3K inhibition. Cancer Res. 2010 Dec 1;70(23):10002-11.
58 Shenoy K, et al. LY303511 enhances TRAIL sensitivity of SHEP-1 neuroblastoma cells via hydrogen peroxide-mediated mitogen-activated protein kinase activation and up-regulation of death receptors. Cancer Res. 2009 Mar 1;69(5):1941-50.
59 El-Kholy W, Macdonald PE, Lin JH, The phosphatidylinositol 3-kinase inhibitor LY294002 potently blocks K(V) currents via a direct mechanism. FASEB J. 2003 Apr;17(6):720-2.
60 Kristof AS, et al. LY303511 (2-piperazinyl-8-phenyl-4H-1-benzopyran-4-one) acts via phosphatidylinositol 3-kinase-independent pathways to inhibit cell proliferation via mammalian target of rapamycin (mTOR)- and non-mTOR-dependent mechanisms. J Pharmacol Exp Ther. 2005 Sep;314(3):1134-43.
61 Hiroyuki Hisamichi, et al. Synthetic studies on novel Syk inhibitors. Part 1: Synthesis and structure-activity relationships of pyrimidine-5-carboxamide derivatives. Bioorg Med Chem. 2005 Aug 15;13(16):4936-51.
62 Lancet 243:49 (1944); J Am Pharm Assoc 40:267 (1951); J Am Coll Toxicol 4:65 (1985)
63 https://clinicaltrials.gov/ct2/show/NCT04900129?term=Diclofenac&cond=covid&draw=2&rank=1
64 Zmijewski M, et al. Application of biocatalysis to drug metabolism: preparation of mammalian metabolites of a biaryl-bis-sulfonamide AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptor potentiator using Actinoplanes missouriensis. Drug Metab Dispos. 2006 Jun;34(6):925-31.
65 Jones N, et al. AMPA receptor potentiation can prevent ethanol-induced intoxication. Neuropsychopharmacology. 2008 Jun;33(7):1713-23.
66 ARYL SULFONOHYDRAZIDES. WO2016198507 A1.
67 Dan Yuan, et al. Anti-inflammatory effects of rhynchophylline and isorhynchophylline in mouse N9 microglial cells and the molecular mechanism. International Immunopharmacology&#x0D; Volume 9, Issues 13–14, December 2009, Pages 1549–1554
68 Houcai Huang, et al. Neuroprotective Effects of Rhynchophylline Against Ischemic Brain Injury via Regulation of the Akt/mTOR and TLRs Signaling Pathways. Molecules 2014, 19 (8): 11196-11210; doi:10.3390/molecules190811196
69 Tai-Hyun Kang, et al. Protective effect of rhynchophylline and isorhynchophylline on in vitro ischemia-induced neuronal damage in the hippocampus: putative neurotransmitter receptors involved in their action. Life Sciences&#x0D; Volume 76, Issue 3, 3 December 2004, Pages 331–343
70 Kinzo Matsumoto, et al. Suppressive effects of isorhynchophylline on 5-HT2A receptor function in the brain: Behavioural and electrophysiological studies. European Journal of Pharmacology&#x0D; Volume 517, Issue 3, 11 July 2005, Pages 191–199
71 Von Nussbaum F, et al. Freezing the Bioactive Conformation to Boost Potency: The Identification of BAY 85-8501, a Selective and Potent Inhibitor of Human Neutrophil Elastase for Pulmonary Diseases. ChemMedChem. 2015 Jul;10(7):1163-73.
72 Tetrahedron Letters 1965: 669
73 Qiang Qv.et al.Selective estrogenic effects of a novel triphenylethylene compound, FC1271a, on bone, cholesterol level, and reproductive tissues in intact and ovariectomized rats. Endocrinology.Feb;141(2):809-20. 25. (2000).
74 Tracy L. Taras et al.In vitro and in vivo biologic effects of Ospemifene (FC-1271a) in breast cancer. The Journal of Steroid Biochemistry and Molecular Biology 77(4-5):271-9,(2001).
75 Unkila M, et, al. Vaginal effects of ospemifene in the ovariectomized rat preclinical model of menopause. J Steroid Biochem Mol Biol. 2013 Nov;138:107-15.
76 Bruyniks N, et, al. Systematic indirect comparison of ospemifene versus local estrogens for vulvar and vaginal atrophy. Climacteric. 2017 Jun; 20(3): 195-204.
77 J Med Chem 29:1553 (1986); J Nat Prod 53:186 (1990)|
78 Min Liu, et al. Intracellular delivery of 10-hydroxycamptothecin&#x0D; with targeted nanostructured lipid carriers against&#x0D; multidrug resistance&#x0D;. Journal of Drug Targeting.
79 Min Liu, et al. Intracellular delivery of 10-hydroxycamptothecin with targeted&#x0D; nanostructured lipid carriers against multidrug resistance. J Drug Target, Early Online: 1–8
80 Yu P, et al. Synthesis and preliminary anticancer evaluation of 10-hydroxycamptothecin analogs. Biol Pharm Bull. 2012;35(8):1295-9.
81 Zhang XW, et al. Differentiation-inducing action of 10-hydroxycamptothecin on human hepatoma Hep G2 cells. Acta Pharmacol Sin. 2000 Apr;21(4):364-8.
82 Zhang XW, et al. Differential regulation of P53, c-Myc, Bcl-2, Bax and AFP protein expression, and caspase activity during 10-hydroxycamptothecin-induced apoptosis in Hep G2 cells. Anticancer Drugs. 2000 Oct;11(9):747-56.
83 Liu M, et al. Intracellular delivery of 10-hydroxycamptothecin with targeted nanostructured lipid carriers against multidrug resistance. J Drug Target. 2016;24(5):433-40.
84 Lin LT, et al. Paris Polyphylla Inhibits Colorectal Cancer Cells via Inducing Autophagy and Enhancing the Efficacy of Chemotherapeutic Drug Doxorubicin. Molecules. 2019 Jun 3;24(11).
85 Stiborova M, et al. Molecular mechanisms of antineoplastic action of an anticancer drug ellipticine. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2006 Jul;150(1):13-23.
86 Stiborova M, et al. Ellipticine cytotoxicity to cancer cell lines - a comparative study. Interdiscip Toxicol. 2011 Jun;4(2):98-105.
87 Stiborova M, et al. The anticancer drug ellipticine activated with cytochrome P450 mediates DNA damage determining its pharmacological efficiencies: studies with rats, Hepatic Cytochrome P450 Reductase Null (HRN?) mice and pure enzymes. Int J Mol Sci. 2014 Dec 25;16(1):284-306.
88 Ghavami M, et al. Biological Studies and Target Engagement of the 2- C-Methyl-d-Erythritol 4-Phosphate Cytidylyltransferase (IspD)-Targeting Antimalarial Agent (1 R,3 S)-MMV008138 and Analogs. ACS Infect Dis. 2018 Apr 13;4(4):549-559.
89 Yao ZK, et al. Determination of the active stereoisomer of the MEP pathway-targeting antimalarial agent MMV008138, and initial structure-activity studies. Bioorg Med Chem Lett. 2015 Apr 1;25(7):1515-9.
90 Schulte ML, et al. Pharmacological blockade of ASCT2-dependent glutamine transport leads to antitumor efficacyin preclinical models. Nat Med. 2018 Feb;24(2):194-202.
91 Bavetsias V, et al. Optimization of imidazo[4,5-b]pyridine-based kinase inhibitors: identification of a dual FLT3/Aurora kinase inhibitor as an orally bioavailable preclinical development candidate for the treatment of acute myeloid leukemia. J Med Chem. 2012 Oct 25;55(20):8721-34.
92 Morshedi D, et al. Cuminaldehyde as the Major Component of Cuminum cyminum, a Natural Aldehyde with Inhibitory Effect on Alpha-Synuclein Fibrillation and Cytotoxicity. J Food Sci. 2015 Oct;80(10):H2336-45.
93 Okawa T, et al. Design, Synthesis, and Evaluation of the Highly Selective and Potent G-Protein-Coupled Receptor Kinase 2 (GRK2) Inhibitor for the Potential Treatment of Heart Failure. J Med Chem. 2017 Aug 24;60(16):6942-6990.
94 Yu Q, et al. Inhibition of prostatic smooth muscle contraction by the inhibitor of G protein-coupled receptor kinase 2/3, CMPD101.Eur J Pharmacol. 2018 Jul 15;831:9-19.
95 Wang Z, et al. Tetrahydroisoquinoline-7-carboxamide Derivatives as New Selective Discoidin Domain Receptor 1 (DDR1) Inhibitors. ACS Med Chem Lett. 2017 Feb 9;8(3):327-332.
96 Fish PV, et al. Selective urokinase-type plasminogen activator inhibitors. 4. 1-(7-sulfonamidoisoquinolinyl)guanidines. J Med Chem. 2007 May 17;50(10):2341-51.
97 Baltatu OC, Iliescu R, Zaugg CE, Reckelhoff JF, Louie P, Schumacher C, Campos LA.&#x0D; Antidiuretic effects of the endothelin receptor antagonist avosentan.&#x0D; Front Physiol. 2012;3:103.
98 Konieczka K, Meyer P, Schoetzau A, Neutzner A, Mozaffarieh M, Flammer J.&#x0D; Effect of avosentan (SPP-301) in porcine ciliary arteries.&#x0D; Curr Eye Res. 2011 Feb;36(2):118-24.
99 Mann JF, Green D, Jamerson K, Ruilope LM, Kuranoff SJ, Littke T, Viberti G; ASCEND Study Group.&#x0D; J Am Soc Nephrol. 2010 Mar;21(3):527-35.
100 Dieterle W, Hengelage T.&#x0D; Absolute bioavailability and pharmacokinetics of avosentan in man.&#x0D; Int J Clin Pharmacol Ther. 2009 Sep;47(9):587-94.
101 Effect of SPP 301, an Endothelin Antagonist, on Intraocular Pressure in Glaucomatous Monkey Eyes By Wang, Rong-Fang; Podos, Steven M.; Serle, Janet B.; Baltatu, Ovidiu C. From Current Eye Research (2011), 36(1), 41-46.
102 Nature 184: 1714 (1959); Biol Pharm Bull 29:684 (2006)
103 Aust J Chem 34:1779 (1981)
104 Van Schaick EA et al. Hemodynamic effects and histamine release elicited by the selective adenosine A3 receptor agonist 2-Cl-IB-MECA in conscious rats. Eur J Pharmacol. 1996 Jul 25;308(3):311-4.
105 Jacobson KA et al. Adenosine A3 receptors: novel ligands and paradoxical effects. Trends Pharmacol Sci. 1998 May;19(5):184-91.
106 Drugs 45:85 (1993); Am J Cardiol 82:59N, 66N (1998);
107 https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=Prednisolone&cntry=&state=&city=&dist=
108 Fales KR, et al. Discovery of N-(6-Fluoro-1-oxo-1,2-dihydroisoquinolin-7-yl)-5-[(3R)-3-hydroxypyrrolidin-1-yl]thiophene-2-sulfonamide (LSN 3213128), a Potent and Selective Nonclassical Antifolate Aminoimidazole-4-carboxamide Ribonucleotide Formyltransferase (AICARFT) Inhibitor Effective at Tumor Suppression in a Cancer Xenograft Model. J Med Chem. 2017 Dec 14;60(23):9599-9616.
109 Zaghloul MS, et al. Crocin attenuates lung inflammation and pulmonary vascular dysfunction in a rat model of bleomycin-induced pulmonary fibrosis. Life Sci. 2019 Aug 26:116794.
110 Chang P, et al. Seizure control by decanoic acid through direct AMPA receptor inhibition. Brain. 2016 Feb;139(Pt 2):431-43.
111 Kim S, et, al. Selective production of decanoic acid from iterative reversal of β-oxidation pathway. Biotechnol Bioeng. 2018 May;115(5):1311-1320.
112 Boison D, et, al. New insights into the mechanisms of the ketogenic diet. Curr Opin Neurol. 2017 Apr;30(2):187-192.
113 Biochem. J. (1990), 270(3), 691-5; Drugs (1986), 31(5), 430-48; J. Pharmacol. Exp. Ther. (1945), 85, 343-5
114 Ring-fused bicyclic pyridyl derivatives as fgfr4 inhibitors. WO 2015059668 A1?
115 Ma L, et al. Selective activation of the M1 muscarinic acetylcholine receptor achieved by allosteric potentiation. Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15950-5.
116 Shirey JK, et al. A selective allosteric potentiator of the M1 muscarinic acetylcholine receptorincreases activity of medial prefrontal cortical neurons and restores impairments in reversal learning. J Neurosci. 2009 Nov 11;29(45):14271-86.
117 Russell JP, et al. Exploring the Potential of RET Kinase Inhibition for Irritable Bowel Syndrome: A Preclinical Investigation in Rodent Models of Colonic Hypersensitivity. J Pharmacol Exp Ther. 2019 Feb;368(2):299-307.
118 Russell JP, et al. Enteric RET inhibition attenuates gastrointestinal secretion and motility via cholinergic signaling in rat colonic mucosal preparations. Neurogastroenterol Motil. 2019 Apr;31(4):e13479.
119 Li NN, et al. Evidence for the Involvement of COX-2/VEGF and PTEN/Pl3K/AKT Pathway the Mechanism of Oroxin B Treated Liver Cancer. Pharmacogn Mag. 2018 Apr-Jun;14(54):207-213.
120 Yang P, et al. Oroxin B selectively induces tumor-suppressive ER stress and concurrently inhibits tumor-adaptive ER stress in B-lymphoma cells for effective anti-lymphoma therapy. Toxicol Appl Pharmacol. 2015 Oct 15;288(2):269-79.
121 Clin Gastroenterol Hepatol 4:1395 (2006); Health Technol Assess 14:#24 (2010)
122 Thorisdottir H, Ratnoff OD, Maniglia AJ. Activation of Hageman factor (factor XII) by bismuth subgallate, a hemostatic agent. J Lab Clin Med. 1988;112(4):481‐486.
123 Puia SA, Renou SJ, Rey EA, Guglielmotti MB, Bozzini CE. Effect of bismuth subgallate (a hemostatic agent) on bone repair; a histologic, radiographic and histomorphometric study in rats. Int J Oral Maxillofac Surg. 2009;38(7):785‐789.
124 Hideshima T, et all. MLN120B, a novel IkappaB kinase beta inhibitor, blocks multiple myeloma cell growth in vitro and in vivo. Clin Cancer Res. 2006 Oct 1;12(19):5887-94.
125 Schopf L, et al. IKKbeta inhibition protects against bone and cartilage destruction in a rat model of rheumatoid arthritis. Arthritis Rheum. 2006 Oct;54(10):3163-73.
126 Ansaldi D, et al. Imaging pulmonary NF-kappaB activation and therapeutic effects of MLN120B and TDZD-8. PLoS One. 2011;6(9):e25093.
127 Nagashima K, et al. Rapid TNFR1-dependent lymphocyte depletion in vivo with a selective chemical inhibitor of IKKbeta. Blood. 2006 Jun 1;107(11):4266-73.
128 Du K, et al. Mitochondria-targeted antioxidant Mito-Tempo protects against acetaminophen hepatotoxicity. Arch Toxicol. 2017 Feb;91(2):761-773.
129 Guo X, et al. Comparative Genotoxicity of TEMPO and 3 of Its Derivatives in Mouse Lymphoma Cells. Toxicol Sci. 2018 May 1;163(1):214-225.
130 Lv H, et al. TEMPO catalyzed oxidative dehydrogenation of hydrazobenzenes to azobenzenes. Org Biomol Chem. 2020 Apr 22.
131 Chen X, et al. Isocitrate dehydrogenase 2 contributes to radiation resistance of oesophageal squamous cell carcinoma via regulating mitochondrial function and ROS/pAKT signalling. Br J Cancer. 2020 May 5.
132 J Heterocyclic Chem 9: 1453 (1972); J Biol Chem 280:19078 (2005); FEBS J 273:2139 (2006)
133 Ohkubo M, et al. Heavy metal chelator TPEN attenuates fura-2 fluorescence changes induced by cadmium, mercury and methylmercury. J Vet Med Sci. 2016 Jun 1;78(5):761-7.
134 Rahal ON, et al. Chk1 and DNA-PK mediate TPEN-induced DNA damage in a ROS dependent manner in human colon cancer cells. Cancer Biol Ther. 2016 Nov;17(11):1139-1148.
135 E Aizenman, et al. Induction of neuronal apoptosis by thiol oxidation: putative role of intracellular zinc release. J Neurochem. 2000 Nov;75(5):1878-88.
136 Zheng MS, et al. Antiviral effect of mangiferin and isomangiferin on herpes simplex virus. Chin Med J (Engl). 1990 Feb;103(2):160-5.
137 Gerassim M Kitanov, et al. Mangiferin and isomangiferin in some Hypericum species. Biochemical Systematics and Ecology&#x0D; Volume 26, Issue 6, 1 September 1998, Pages 647–653
138 Fraveto A, et al, Sensitivity of Human Intrahepatic Cholangiocarcinoma Subtypes to Chemotherapeutics and Molecular Targeted Agents: A Study on Primary Cell Cultures. PLoS One. 2015 Nov 16;10(11):e0142124.
139 Hoch L, et al. MRT-92 inhibits Hedgehog signaling by blocking overlapping binding sites in the transmembrane domain of the Smoothened receptor. FASEB J. 2015 May;29(5):1817-29.
140 Ma W, et al. Reduced Smoothened level rescued Aβ-induced memory deficits and neuronal inflammation in animal models of Alzheimer's disease. J Genet Genomics. 2018 May 20;45(5):237-246.
141 J Org Chem 25:1073 (1960); Jacs 99:6639 (1977)
142 JACS 52:2461 (1930); J Chem Soc 1938: 513
143 Linz K, et al. Cebranopadol: a novel potent analgesic nociceptin/orphanin FQ peptide and opioid receptor agonist. J Pharmacol Exp Ther. 2014 Jun;349(3):535-48.
144 de Guglielmo G, et al. Cebranopadol Blocks the Escalation of Cocaine Intake and Conditioned Reinstatement of Cocaine Seeking in Rats. J Pharmacol Exp Ther. 2017 Sep;362(3):378-384.
145 Satat K, et al. Evaluation of cebranopadol, a dually acting nociceptin/orphanin FQ and opioid receptor agonist in mouse models of acute, tonic, and chemotherapy-induced neuropathic pain. Inflammopharmacology. 2017 Oct 25.
146 Christopher M. YATES. Metalloenzyme inhibitor compounds. WO2018165520A1.
147 Zhao G, et al. Discovery of a Highly Selective NAMPT Inhibitor That Demonstrates Robust Efficacy and Improved Retinal Toxicity with Nicotinic Acid Coadministration. Mol Cancer Ther. 2017 Dec;16(12):2677-2688.
148 Stella W Nowotarska, et al. Mechanisms of Antimicrobial Action of Cinnamon and Oregano Oils, Cinnamaldehyde, Carvacrol, 2,5-Dihydroxybenzaldehyde, and 2-Hydroxy-5-Methoxybenzaldehyde Against Mycobacterium Avium Subsp. Paratuberculosis (Map). Foods. 2017 Aug 24;6(9):72.
149 Andrea Schabauer, et al. Gentisaldehyde and Its Derivative 2,3-Dihydroxybenzaldehyde Show Antimicrobial Activities Against Bovine Mastitis Staphylococcus aureus. Front Vet Sci. 2018 Jul 11;5:148.
150 https://clinicaltrials.gov/ct2/show/NCT04394117?term=Eprosartan&cond=Covid19&draw=2&rank=2
151 Albright JD, et al. 5-Fluoro-2-methyl-N-[4-(5H-pyrrolo[2,1-c]-[1, 4]benzodiazepin-10(11H)-ylcarbonyl)-3-chlorophenyl]benzamide (VPA-985): an orally active arginine vasopressin antagonist with selectivity for V2 receptors. J Med Chem. 1998 Jul 2;41(14):2442-4.
152 Ghali JK, et al. Lixivaptan, a non-peptide vasopressin V2 receptor antagonist for the potential oral treatment of hyponatremia. IDrugs. 2010 Nov;13(11):782-92.
153 Beerman TA et al. Netropsin and bis-netropsin analogs as inhibitors of the catalytic activity of mammalian DNA topoisomerase II and topoisomerase cleavable complexes. Biochim Biophys Acta. 1991 Aug 27;1090(1):52-60.
154 Grant MA, et al. Netropsin improves survival from endotoxaemia by disrupting HMGA1 binding to the NOS2 promoter. Biochem J. 2009 Feb 15;418(1):103-12.
155 Mishra K et al. Netropsin, a minor groove binding ligand: a potential radioprotective agent. Radiat Res. 2009 Dec;172(6):698-705.
156 Tumang J, et al. PF-06840003: a highly selective IDO-1 inhibitor that shows good in vivo efficacy in combination with immune checkpoint inhibitors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr4863.
157 Indoleamine 2,3-Dioxygenase (IDO-1) Inhibitor 3-(5-Fluoro-1H-indol-3-yl)pyrrolidine-2,5-dione (EOS200271/PF-06840003) and Its Characterization as a Potential Clinical Candidate. J Med Chem. 2017 Dec 14;60(23):9617-9629.
158 Hong YR, et al. [(4-Hydroxyl-benzo[4,5]thieno[3,2-c]pyridine-3-carbonyl)-amino]-acetic acid derivatives; HIF prolyl 4-hydroxylase inhibitors as oral erythropoietin secretagogues. Bioorg Med Chem Lett. 2013 Nov 1;23(21):5953-7.
159 Hsieh MM, et al. HIF prolyl hydroxylase inhibition results in endogenous erythropoietin induction, erythrocytosis, and modest fetal hemoglobin expression in rhesus macaques. Blood. 2007 Sep 15;110(6):2140-7.
160 Bernhardt WM, et, al. Inhibition of prolyl hydroxylases increases erythropoietin production in ESRD. J Am Soc Nephrol. 2010 Dec;21(12):2151-6.
161 Katayama Y, et al. Inhibitory effects of Vesnarinone on cloned cardiac delayed rectifier K(+) channels expressed in a mammalian cell line. J Pharmacol Exp Ther. 2000 Jul;294(1):339-46.
162 Inage M, et al. Vesnarinone represses the fibrotic changes in murine lung injury induced by bleomycin. Int J Biol Sci. 2009;5(4):304-10.
163 Cavusoglu E, et al. Vesnarinone: a new inotropic agent for treating congestive heart failure. J Card Fail. 1995 Jun;1(3):249-57.
164 Matsumori A, et al. Vesnarinone, a new inotropic agent, inhibits cytokine production by stimulated human blood from patients with heart failure. Circulation. 1994 Mar;89(3):955-8.
165 J Chem Soc 1954:1066; Ann Rev Plant Physiol 8:181 (1957); J Agric Food Chem 6:184 (1958); J Exp Botany,49:89 (1998)
166 Tavazoie MF, et al. LXR/ApoE Activation Restricts Innate Immune Suppression in Cancer. Cell. 2018 Feb 8;172(4):825-840.e18.
167 Zhang, Chao, et al. Kinase modulation for the treatment of leukemias. From PCT Int. Appl. (2012), WO 2012158957 A2 20121122.
168 Zhang Chao, et al. 7-Azaindole derivatives and their preparation, pharmaceutical compositions and use for modulating c-kit and c-fms activity. From PCT Int. Appl. (2007), WO 2007013896 A2 20070201.
169 Matsumoto T, et al. Improvement of motor nerve conduction velocity in diabetic rats requires normalization of the polyol pathway metabolites flux. J Pharmacol Sci. 2009 Feb;109(2):203-10.
170 Toyoda F, et al. Effect of ranirestat, a new aldose reductase inhibitor, on diabetic retinopathy in SDT rats. J Diabetes Res. 2014;2014:672590.
171 Hefner G, et al. Melperone but not bisoprolol or metoprolol is a clinically relevant inhibitor of CYP2D6: evidence from a therapeutic drug monitoring survey. J Neural Transm (Vienna). 2015 Nov;122(11):1609-17.
172 Bobo WV, et al. Melperone, an aytpical antipsychotic drug with clozapine-like effect on plasma prolactin: contrast with typical neuroleptics. Hum Psychopharmacol. 2009 Jul;24(5):415-22.
173 Profiles Drug Subs 6:457 (1977); N Engl J Med 311:1353 (1984)
174 J Am Oil Chem Soc 51:321 (1974)
175 Canal-Raffin M, et al. Cytotoxicity of folpet fungicide on human bronchial epithelial cells. Toxicology. 2008 Jul 30;249(2-3):160-6.
176 https://clinicaltrials.gov/ct2/show/NCT04532931?term=Amodiaquine&cond=covid&draw=2&rank=1
177 Cowburn AS, et al. z-VAD-fmk augmentation of TNF alpha-stimulated neutrophil apoptosis is compound specific and does not involve the generation of reactive oxygen species.
178 Yee SB, et al. zVAD-fmk, unlike BocD-fmk, does not inhibit caspase-6 acting on 14-3-3/Bad pathway in apoptosis of p815 mastocytoma cells. Exp Mol Med. 2006 Dec 31;38(6):634-42.
179 Sheen-Chen SM, et al. Effect of Boc-D-Fmk on hepatocyte apoptosis after bile duct ligation in rat and survival rate after endotoxin challenge. J Gastroenterol Hepatol. 2008 Aug;23(8 Pt 1):1276-9.
180 Chan YM, et al. Inhibition of caspases promotes long-term survival and reinnervation by axotomized spinal motoneurons of denervated muscle in newborn rats. Exp Neurol. 2003 Jun;181(2):190-203.
181 Anesth. Analg. (2002), 95(4), 789-790; Toxicol. Appl. Pharmacol. (1964), 6(1), 37-47; Arzneim. Forsch. (1963), 13(No. 3), 205-11
182 Chemotherapy 14:195 (1969); Br Med J 328:545 (2004)
183 Cheng K, et al. Discovery of small-molecule inhibitors of the TLR1/TLR2 complex. Angew Chem Int Ed Engl. 2012 Dec 3;51(49):12246-9.
184 Aliakbar Tehrani Z, et al. Comparison of gas phase intrinsic properties of cytosine and thymine nucleobases with their O-alkyl adducts: different hydrogen bonding preferences for thymine versus O-alkyl thymine. J Mol Model. 2013;19(8):2993‐3005.
185 https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=SODIUM+GLUCONATE&cntry=&state=&city=&dist=&Search=Search
186 Kay GG, Harris AG. Loratadine: a non-sedating antihistamine. Review of its effects on cognition, psychomotor performance, mood and sedation. Clin Exp Allergy. 1999 Jul;29 Suppl 3:147-50.
187 Menardo JL, Horak F, Danzig MR, Czarlewski W. A review of loratadine in the treatment of patients with allergic bronchial asthma. Clin Ther. 1997 Nov-Dec;19(6):1278-93; discussion 1523-4.
188 Monroe EW. Loratadine in the treatment of urticaria. Clin Ther. 1997 Mar-Apr;19(2):232-42.
189 Haria M, Fitton A, Peters DH. Loratadine. A reappraisal of its pharmacological properties and therapeutic use in allergic disorders. Drugs. 1994 Oct;48(4):617-37.
190 Roman IJ, Danzig MR. Loratadine. A review of recent findings in pharmacology, pharmacokinetics, efficacy, and safety, with a look at its use in combination with pseudoephedrine. Clin Rev Allergy. 1993 Spring;11(1):89-110.
191 Shahen M, et al. Dengue virus causes changes of MicroRNA-genes regulatory network revealing potential targets for antiviral drugs. BMC Syst Biol. 2018 Jan 4;12(1):2.
192 Kleine-Tebbe J, et al. Inhibition of IgE- and non-IgE-mediated histamine release from human basophil leukocytes in vitro by a histamine H1-antagonist, desethoxycarbonyl-loratadine. J Allergy Clin Immunol. 1994;93(2):494-500. |Allergy (1987), 42(1), 57-63; Agents Actions (1984), 14(5-6), 590-7; Ann. Allergy (1987), 58(6), 407-11
193 Phytochemistry 35: 1567 (1994)
194 Headache 22:167 (1982); Clin Pharmacokinet10:334 (1985); Teratology 51:344 (1995)
195 https://clinicaltrials.gov/ct2/show/NCT04784754?term=melatonin&cond=covid&draw=2&rank=2
196 C Metcalfe, et al. Abstract P5-04-07: GDC-9545: A novel ER antagonist and clinical candidate that combines desirable mechanistic and pre-clinical DMPK attributes
197 Chen DF, et al. Anti-AIDS agents--XXVI. Structure-activity correlations of gomisin-G-related anti-HIV lignans from Kadsura interior and of related synthetic analogues. Bioorg Med Chem. 1997 Aug;5(8):1715-23.
198 Ikeya Y, et al. The constituents of Schizandra chinensis Baill. I. Isolation and structure determination of five new lignans, gomisin A, B, C, F and G, and the absolute structure of schizandrin. Chem Pharm Bull (Tokyo). 1979 Jun;27(6):1383-94.
199 Am Rev Respir Dis 137(suppl):427 (1988); Eur J Pharmacol 155:117 (1988); Biochem Pharmacol 38:2291 (1989); Agents Actions 29:299 (1990)
200 Shi Y, et al. Gboxin is an oxidative phosphorylation inhibitor that targets glioblastoma. Nature. 2019 Mar;567(7748):341-346.
201 Okoye-Okafor UC, et al. New IDH1 mutant inhibitors for treatment of acute myeloid leukemia. Nat Chem Biol. 2015 Nov;11(11):878-86.
202 Budke B, et al. An optimized RAD51 inhibitor that disrupts homologous recombination without requiring Michael acceptor reactivity. J Med Chem. 2013 Jan 10;56(1):254-63.
203 Chen Z, et al. 1-Benzyl-3-cetyl-2-methylimidazolium iodide (NH125) induces phosphorylation of eukaryotic elongation factor-2 (eEF2): a cautionary note on the anticancer mechanism of an eEF2 kinase inhibitor. J Biol Chem. 2011 Dec 23;286(51):43951-8.
204 Kodama T, et al. Mechanisms underlying the relaxation by A484954, a eukaryotic elongation factor 2 kinase inhibitor, in rat isolated mesenteric artery. J Pharmacol Sci. 2018 May;137(1):86-92.
205 Kameshima S, et al. Eukaryotic elongation factor 2 kinase mediates monocrotaline-induced pulmonary arterial hypertension via reactive oxygen species-dependent vascular remodeling. Am J Physiol Heart Circ Physiol. 2015 May 15;308(10):H1298-305.
206 Min SH, et al. Pharmacological targeting reveals distinct roles for CXCR2/CXCR1 and CCR2 in a mouse model of arthritis.Biochem Biophys Res Commun. 2010 Jan 1;391(1):1080-6.
207 Wisniewski T, et al. Assessment of chemokine receptor function on monocytes in whole blood: In vitro and ex vivo evaluations of a CCR2 antagonist.J Immunol Methods. 2010 Jan 31;352(1-2):101-10.
208 Pharmacol. Biochem. Prop. Drug Subst. (1977), 1, 183-213; Drugs (1977), 13(4), 241-65; Prostaglandins (1974), 6(2), 107-13
209 Sonneveld, E., et al., Development of androgen- and estrogen-responsive bioassays, members of a panel of human cell line-based highly selective steroid-responsive bioassays. Toxicol Sci, 2005. 83(1): p. 136-48.
210 Torri V,. Cyproterone acetate in the therapy of prostate carcinoma. Arch Ital Urol Androl. 2005;77(3):157-163.
211 Chen L, et al. Cyproterone acetate enhances TRAIL-induced androgen-independent prostate cancer cell apoptosis via up-regulation of death receptor 5. BMC Cancer. 2017;17(1):179. Published 2017 Mar 7.
212 Migally N. Effect of cyproterone acetate on the structure of the adrenal cortex. Arch Androl. 1979;2(2):109-115.
213 Takiguchi M, et al. Cyproterone acetate induces a cellular tolerance to cadmium in rat liver epithelial cells involving reduced cadmium accumulation. Toxicology. 2001;165(1):13-25. |Arzneim Forsch 23:1550 (1973); J Steroid Biochem 19:591 (1983)
214 Usman Bacha, et al. Development of broad-spectrum halomethyl ketone inhibitors against coronavirus main protease 3CL(pro). Chem Biol Drug Des. 2008 Jul;72(1):34-49.
215 Epilepsia (1995), 36 Suppl 2S2-12; Drugs (1993), 46(3), 409-27; Curr. Probl. Epilepsy (1986), 4, 147-63
216 Harris PA, et al. Discovery of a First-in-Class Receptor Interacting Protein 1 (RIP1) Kinase Specific Clinical Candidate (GSK2982772) for the Treatment of Inflammatory Diseases. J Med Chem. 2017 Feb 23;60(4):1247-1261.
217 Br Heart J 69:293 (1993); Kidney Int. 65:1240 (2004); J Biol Chem 283:4588 (2008)
218 May PC1, et al. The potent BACE1 inhibitor LY2886721 elicits robust central Aβ pharmacodynamic responses in mice, dogs, and humans. J Neurosci. 2015 Jan 21;35(3):1199-210.
219 Dzyurkevich MS, et al. Pyridoxine dipharmacophore derivatives as potent glucokinase activators for the treatment of type 2 diabetes mellitus. Sci Rep. 2017 Nov 22;7(1):16072.
220 Amin NB, et al. Two dose-ranging studies with PF-04937319, a systemic partial activator of glucokinase, as add-on therapy to metformin in adults with type 2 diabetes. Diabetes Obes Metab. 2015 Aug;17(8):751-9.
221 Petersen M, et al. Oral administration of GW788388, an inhibitor of TGF-beta type I and II receptor kinases, decreases renal fibrosis. Kidney Int, 2008, 73(6), 705-715.
222 Tan SM, et al. Targeted inhibition of activin receptor-like kinase 5 signaling attenuates cardiac dysfunction following myocardial infarction. Am J Physiol Heart Circ Physiol, 2010, 298(5), H1415-1425.
223 Gellibert F, et al. Discovery of 4-{4-[3-(pyridin-2-yl)-1H-pyrazol-4-yl]pyridin-2-yl}-N-(tetrahydro-2H- pyran-4-yl)benzamide (GW788388): a potent, selective, and orally active transforming growth factor-beta type I receptor inhibitor. J Med Chem. 2006, 49
224 Arzneim Forsch 46:153 (1996); J Allergy Clin Immunol 98:1062 (1996)
225 Biochem Biophys Res Commun 13:394 (1963); J Pharmacol 14:47 (1983)|
226 Filipe Marques Gonçalves, et al. Signaling pathways underlying the antidepressant-like effect of inosine in mice. Purinergic Signal. 2017 Jun; 13(2): 203–214.
227 Ajith A. Welihinda, et al. The adenosine metabolite inosine is a functional agonist of the adenosine A2A receptor with a unique signaling bias. Cell Signal. 2016 Jun; 28(6): 552–560.
228 Francisney Pinto Nascimento, et al. Adenosine A1 receptor-dependent antinociception induced by inosine in mice: pharmacological, genetic and biochemical aspects. Mol Neurobiol. 2015;51(3):1368-78.
229 Sara Cipriani, et al. Protection by inosine in a cellular model of Parkinson’s disease. Neuroscience. 2014 Aug 22; 274: 242–249.
230 Mandal P, et al. RIP3 induces apoptosis independent of pronecrotic kinase activity. Mol Cell. 2014 Nov 20;56(4):481-95.
231 Arora D, et al. Deltamethrin induced RIPK3-mediated caspase-independent non-apoptotic cell death in rat primary hepatocytes. Biochem Biophys Res Commun. 2016 Oct 14;479(2):217-223.
232 Campos CA, et al. Anti-hyperalgesic and anti-inflammatory effects of citral with β-cyclodextrin and hydroxypropyl-β-cyclodextrin inclusion complexes in animal models. Life Sci. 2019 Jul 15;229:139-148.
233 Drugs (1978), 16(3), 177-201; Arzneim. Forsch. (1975), 25(2), 224-30; J. Med. Chem. (1969), 12(5), 784-91
234 Regul Toxicol Pharmacol 36:198 (2002)
235 Zhang Y, et al. Suppression of prostate cancer progression by cancer cell stemness inhibitor napabucasin. Cancer Med. 2016 Jun;5(6):1251-8.
236 Zhao Y, et al. Mechanisms and Clinical Application of Tetramethylpyrazine (an Interesting Natural Compound Isolated from Ligusticum Wallichii): Current Status and Perspective. Oxid Med Cell Longev. 2016;2016:2124638.
237 Wu W, et al. Tetramethylpyrazine protects against scopolamine-induced memory impairments in rats by reversing the cAMP/PKA/CREB pathway. Behav Brain Res. 2013 Sep 15;253:212-6.
238 Kao TK, et al. Tetramethylpyrazine reduces cellular inflammatory response following permanent focal cerebral ischemia in rats. Exp Neurol. 2013 Sep;247:188-201.
239 Baron BM, et al. Potent indole- and quinoline-containing N-methyl-D-aspartate antagonists acting at the strychnine-insensitive glycine binding site. J Pharmacol Exp Ther. 1992 Sep;262(3):947-56.
240 Wright SW, et al. 3-(2-carboxyethyl)-4,6-dichloro-1H-indole-2-carboxylic acid: an allosteric inhibitor of fructose-1,6-bisphosphatase at the AMP site. Bioorg Med Chem Lett. 2003 Jun 16;13(12):2055-8.
241 Harden TK. Enigmatic GPCR finds a stimulating drug. Sci Signal. 2013 Oct 22;6(298):pe34.
242 Piali L, et, al. Cenerimod, a novel selective S1P 1 receptor modulator with unique signaling properties. Pharmacol Res Perspect. 2017 Dec;5(6):e00370.
243 Kano M, et, al. Attenuation of murine sclerodermatous models by the selective S1P 1 receptor modulator cenerimod. Sci Rep. 2019 Jan 24;9(1):658.
244 J Toxicol Clin Toxicol 36:713 (1998); J Emergency Med 41:166 (2011)
245 https://clinicaltrials.gov/ct2/show/NCT04483960?term=Nafamostat&cond=Covid19&draw=2&rank=7
246 Myers SM, et al. Identification of a novel orally bioavailable ERK5 inhibitor with selectivity over p38α and BRD4. Eur J Med Chem. 2019 May 25;178:530-543.
247 D. W. Yesair, et al. Relationship of Phthalanilide-Lipid Complexes to Uptake and Retention of 2-Chloro-4′,4″-di(2-imidazolin-2-yl)terephthalanilide (NSC 60339) by Sensitive and Resistant P388 Leukemia Cells. CANCER RESEARCH 26 Part 1: 202-207, February 1966.
248 Yesair DW, et al. The retention or efflux of phthalanilide (NSC 60339)-lipid complexes by sensitive or resistant murine tumor cells and Escherichia coli B. Cancer Res. 1968 Feb;28(2):314-9.
249 Haynes KM, et al. Identification and Structure-Activity Relationships of Novel Compounds that Potentiate the Activities of Antibiotics in Escherichia coli. J Med Chem. 2017 Jul 27;60(14):6205-6219.
250 Abdali N, et al. Reviving Antibiotics: Efflux Pump Inhibitors That Interact with AcrA, a Membrane Fusion Protein of the AcrAB-TolC Multidrug Efflux Pump. ACS Infect Dis. 2017 Jan 13;3(1):89-98.
251 Feng Gao, et al. Synthesis, isolation, stereostructure and cytotoxicity of paclitaxel analogs from cephalomannine.Fitoterapia. 2013 Oct;90:79-84.
252 Jianhua Li, et al. Microbial transformation of cephalomannine by Luteibacter sp. J Nat Prod. 2007 Dec;70(12):1846-9.
253 Larsen IK, et al. Caracemide, a site-specific irreversible inhibitor of protein R1 of Escherichia coli ribonucleotide reductase. J Biol Chem. 1992 Jun 25;267(18):12627-31.
254 Slatter JG, et al. Studies on the metabolic fate of caracemide, an experimental antitumor agent, in the rat. Evidence for the release of methyl isocyanate in vivo. Chem Res Toxicol. 1993 May-Jun;6(3):335-40.
255 Engers JL, et al. Discovery of a Selective and CNS Penetrant Negative Allosteric Modulator of Metabotropic Glutamate Receptor Subtype 3 with Antidepressant and Anxiolytic Activity in Rodents. J Med Chem. 2015 Sep 24;58(18):7485-500.
256 J Chem Soc 67: 649 (1895)
257 Escaich S, et al. The MUT056399 inhibitor of FabI is a new antistaphylococcal compound. Antimicrob Agents Chemother. 2011 Oct;55(10):4692-7.
258 Schiebel J, et al. An ordered water channel in Staphylococcus aureus FabI: unraveling the mechanism of substrate recognitionand reduction. Biochemistry. 2015 Mar 17;54(10):1943-55.
259 Moasser MM, et al. Inhibition of Src kinases by a selective tyrosine kinase inhibitor causes mitotic arrest. Cancer Res. 1999 Dec 15;59(24):6145-52.
260 Kraus GA, et al. New effective inhibitors of the Abelson kinase. Bioorg Med Chem. 2010 Sep 1;18(17):6316-21.
261 Windham TC, et al. Src activation regulates anoikis in human colon tumor cell lines. Oncogene. 2002 Nov 7;21(51):7797-807.
262 Hutchinson JH, et al. Nonpeptide alphavbeta3 antagonists. 8. In vitro and in vivo evaluation of a potent alphavbeta3 antagonist for the prevention and treatment of osteoporosis. J Med Chem. 2003 Oct 23;46(22):4790-8.
263 Pickarski M, et al. Orally active αvβ3 integrin inhibitor MK-0429 reduces melanoma metastasis. Oncol Rep. 2015 Jun;33(6):2737-45.
264 Xiaoyan Zhou, et al. An integrin antagonist (MK-0429) decreases proteinuria and renal fibrosis in the ZSF1 rat diabetic nephropathy model. Pharmacol Res Perspect. 2017 Oct;5(5):e00354.
265 He M, et al. A review on the pharmacological effects of vitexin and isovitexin. Fitoterapia. 2016 Dec;115:74-85.
266 Lima LKF, et al. A Brief Review on the Neuroprotective Mechanisms of Vitexin. Biomed Res Int. 2018 Dec 5;2018:4785089.
267 https://clinicaltrials.gov/ct2/show/NCT04252274?term=Darunavir&cond=covid&draw=2&rank=3
268 Therapie 30:207, 259 (1975); Drugs 33:430 (1987)
269 Massey AJ, et al. A novel, small molecule inhibitor of Hsc70/Hsp70 potentiates Hsp90 inhibitor induced apoptosis in HCT116 colon carcinoma cells. Cancer Chemother Pharmacol. 2010 Aug;66(3):535-45.
270 Yang X, et al. Heat Shock Cognate 70 Inhibitor, VER-155008, Reduces Memory Deficits and Axonal Degeneration in a Mouse Model of Alzheimer's Disease. Front Pharmacol. 2018 Jan 30;9:48.
271 Kita K, et al. Heat shock protein 70 inhibitors suppress androgen receptor expression in LNCaP95 prostate cancer cells. Cancer Sci. 2017 Sep;108(9):1820-1827.
272 Fukuda I, et al. Ginkgolic acid inhibits protein SUMOylation by blocking formation of the E1-SUMO intermediate. Chem Biol. 2009 Feb 27;16(2):133-40.
273 Lü JM, et al. Ginkgolic acid inhibits HIV protease activity and HIV infection in vitro. Med Sci Monit. 2012 Aug;18(8):BR293-298.
274 Zhou C, et al. Antitumor effects of ginkgolic acid in human cancer cell occur via cell cycle arrest and decrease the Bcl-2/Bax ratio to induce apoptosis. Chemotherapy. 2010;56(5):393-402.
275 Qiu F, et al. Pharmacological inhibition of SUMO-1 with ginkgolic acid alleviates cardiac fibrosis induced by myocardial infarction in mice. Toxicol Appl Pharmacol. 2018 Apr 15;345:1-9.
276 Korean J Food Sci Technol 40:707 (2008)
277 https://clinicaltrials.gov/ct2/show/NCT04865029?term=ESTRADIOL&cond=covid&draw=2&rank=1
278 Estrada AA, et al. Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. J Med Chem. 2014 Feb 13;57(3):921-36.
279 Rohner A, et al. Effective targeting of Hedgehog signaling in a medulloblastoma model with PF-5274857, a potent and selective Smoothened antagonist that penetrates the blood-brain barrier. Mol Cancer Ther. 2012, 11(1), 57-65.
280 Schulze-Topphoff, Ulf., et al. Laquinimod, a quinoline-3-carboxamide, induces type II myeloid cells that modulate central nervous system autoimmunity. PLoS One (2012), 7(3), e33797.
281 Toubi E, et al. Laquinimod modulates B cells and their regulatory effects on T cells in Multiple Sclerosis. J Neuroimmunol. 2012 Oct 15;251(1-2):45-54.
282 Brück W, et al. Reduced astrocytic NF-κB activation by laquinimod protects from cuprizone-induced demyelination. Acta Neuropathol. 2012 Sep;124(3):411-24.
283 https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=ESTRADIOL+ACETATE&cntry=&state=&city=&dist=
284 https://clinicaltrials.gov/ct2/show/NCT04498936?term=Sofosbuvir&cond=covid&draw=2&rank=4
285 Postgrad Med J 48:304 (1972); Arch Ophthalmol 108:520 (1990)
286 Vianello P, et al. Discovery of a Novel Inhibitor of Histone Lysine-Specific Demethylase 1A (KDM1A/LSD1) as Orally Active Antitumor Agent. J Med Chem. 2016 Feb 25;59(4):1501-17.
287 Handeli S, et al. A small-molecule inhibitor of Tcf/beta-catenin signaling down-regulates PPARgamma and PPARdelta activities. Mol Cancer Ther. 2008 Mar;7(3):521-9.
288 Wu MY, et al. FH535 inhibited metastasis and growth of pancreatic cancer cells. Onco Targets Ther. 2015 Jul 6;8:1651-70.
289 Liu L, et al. FH535, a β-catenin pathway inhibitor, represses pancreatic cancer xenograft growth and angiogenesis. Oncotarget. 2016 Jul 26;7(30):47145-47162.
290 Atsuko Kita, et al. Antianxiety and antidepressant-like effects of AC-5216, a novel mitochondrial benzodiazepine receptor ligand. Br J Pharmacol. 2004 Aug;142(7):1059-72.
291 Marcus Karlstetter, et al. Translocator protein (18 kDa) (TSPO) is expressed in reactive retinal microglia and modulates microglial inflammation and phagocytosis. J Neuroinflammation. 2014 Jan 8;11:3.
292 Li-Ming Zhang, et al. Involvement of allopregnanolone in the anti-PTSD-like effects of AC-5216. J Psychopharmacol. 2016 May;30(5):474-81.
293 Zhi-Kun Qiu, et al. The antidepressant-like activity of AC-5216, a ligand for 18KDa translocator protein (TSPO), in an animal model of diabetes mellitus. Sci Rep. 2016 Nov 25;6:37345.
294 Eur J Pharmacol 111:191 (1985); Physiol Behav 61:563 (1997); 83:456 (2006)
295 J Am Chem Soc 57:959 (1954); J.Pharmacol Exp Ther 283 979 (1997)
296 J Org Chem 16: 216 (1951)
297 Stud. Med. Chem. (1996), 1, 331-353; J. Pharmacol. Exp. Ther. (1957), 120, 399-407; Dtsch. Med. Wochenschr. (1955), 80, 351-3
298 Winter GE, et al. BET Bromodomain Proteins Function as Master Transcription Elongation Factors Independent of CDK9 Recruitment. Mol Cell. 2017 Jul 6;67(1):5-18.e19.
299 Penning TD, et al. Optimization of phenyl-substituted benzimidazole carboxamide poly(ADP-ribose) polymerase inhibitors: identification of (S)-2-(2-fluoro-4-(pyrrolidin-2-yl)phenyl)-1H-benzimidazole-4-carboxamide (A-966492), a highly potent and efficacious
300 Fleischer TC, et al. Chemical proteomics identifies Nampt as the target of CB30865, an orphan cytotoxic compound. Chem Biol. 2010 Jun 25;17(6):659-664.
301 Skelton LA, et al. Cell cycle effects of CB30865, a lipophilic quinazoline-based analogue of the antifolate thymidylate synthase inhibitor ICI 198583 with an undefined mechanism of action. Cytometry. 1998 Sep 1;33(1):56-66.
302 Wang TX, et al. Prosapogenin A induces apoptosis in human cancer cells in vitro via inhibition of the STAT3 signaling pathway and glycolysis. Oncol Lett. 2013 Nov;6(5):1323-1328.
303 Xu S, et al. An EP4 Antagonist ONO-AE3-208 Suppresses Cell Invasion, Migration, and Metastasis of Prostate Cancer. Cell Biochem Biophys. 2014 Apr 18.
304 Ren Y, et al. Prostaglandin E2 mediates connecting tubule glomerular feedback. Hypertension. 2013 Dec;62(6):1123-8.
305 Xu S, et al. Inhibitory effect of ONO-AE3-208 on the formation of bone metastasis of prostate cancer in mice. Zhonghua Nan Ke Xue. 2014 Aug;20(8):684-9.
306 Thieme K, et al. EP4 inhibition attenuates the development of diabetic and non-diabetic experimental kidney disease. Sci Rep. 2017 Jun 13;7(1):3442.
307 Dermatol. Clin. (2011), 29, 69-73; Drug Metab. Rev. (1990), 22(2-3), 161-78; Arch. Exp. Pathol. Pharmakol. (1934), 177, 103-12
308 Efron P, et al. Anaphylactic reaction to isosulfan blue used for sentinel node biopsy: case report and literature review. Breast J. 2002 Nov-Dec;8(6):396-9.
309 Laurie SA, et al. Anaphylaxis to isosulfan blue. Ann Allergy Asthma Immunol. 2002 Jan;88(1):64-6.
310 Carboni JM, et al. BMS-754807, a small molecule inhibitor of IGF-1R/IR. Mol Cancer Ther, 2009, 8(12), 3341-3349.
311 Wittman MD, et al. Discovery of a 2,4-disubstituted pyrrolo[1,2-f][1,2,4]triazine inhibitor (BMS-754807) of IGF-1R kinase in clinical development. J Med Chem, 2009, 52(23), 7360-7363.
312 Kolb EA, et al. Initial testing (stage 1) of the IGF-1 receptor inhibitor BMS-754807 by the pediatric preclinical testing program. Pediatr Blood Cancer, 2011, 56(4), 595-603.
313 Franks SE, et al. BMS-754807 is cytotoxic to non-small cell lung cancer cells and enhances the effects of platinum chemotherapeutics in the human lung cancer cell line A549. BMC Res Notes. 2016 Mar 1;9:134.
314 Hasegawa, K., et al., Wnt signaling orchestration with a small molecule DYRK inhibitor provides long-term xeno-free human pluripotent cell expansion. Stem Cells Transl Med, 2012. 1(1): p. 18-28.
315 Miyabayashi, T., et al., Indole derivatives sustain embryonic stem cell self-renewal in long-term culture. Biosci Biotechnol Biochem, 2008. 72(5): p. 1242-8.
316 IDrugs (2004), 7(1), 64-69; Cancer Chemother. Pharmacol. (2003), 52(Suppl. 1), S3-S15; Anticancer Res. (1991), 11(2), 773-6.|
317 Parker AR, et al. BNP7787-mediated modulation of paclitaxel- and cisplatin-induced aberrant microtubule protein polymerization in vitro. Mol Cancer Ther. 2010 Sep;9(9):2558-2567.
318 Hausheer FH, et al.Mechanistic study of BNP7787-mediated cisplatin nephroprotection: modulation of gamma-glutamyl transpeptidase. Cancer Chemother Pharmacol. 2010 Apr;65(5):941-951.
319 Cutler MJ, et al. In vitro and in vivo assessment of renal drug transporters in the disposition of mesna and dimesna. J Clin Pharmacol. 2012 Apr;52(4):530-542.
320 Habs MR,et al. Prevention of urinary bladder tumors in cyclophosphamide-treated rats by additional medication with the uroprotectors sodium 2-mercaptoethane sulfonate (mesna) and disodium 2,2'-dithio-bis-ethane sulfonate (dimesna). Cancer. 1983 Feb 15;51(4):606-609.
321 Lorenz. et al. Oxyresveratrol and resveratrol are potent antioxidants and free radical scavengers: Effect on nitrosative and oxidative stress derived from microglial cells. Nitric Oxide 9(2) 64-76 (2003).
322 Kim, Y.M., Yun, J., Lee, C., et al. Oxyresveratrol and hydroxystilbene compounds. Inhbitory effect on tyrosinase and mechanism of action. J Biol Chem277(18) 16340-16344 (2002).
323 Shaida A Andrabi et al. Oxyresveratrol (trans-2,3′,4,5′-tetrahydroxystilbene) is neuroprotective and inhibits the apoptotic cell death in transient cerebral ischemia. Brain Res, 2004 Aug 13, 1017(1-2):98-107.
324 Vimolmas Lipipun, et al. Topical cream-based oxyresveratrol in the treatment of cutaneous HSV-1 infection in mice. Antiviral Res. 2011 Aug;91(2):154-60.
325 Teppo O Leino, et al. Azulene-based Compounds for Targeting Orexin Receptors. Eur J Med Chem. 2018 Sep 5;157:88-100.
326 Julia Peet, et al. Antiretroviral (HIV-1) Activity of Azulene Derivatives. Bioorg Med Chem. 2016 Apr 15;24(8):1653-7.
327 David A. Becker, et al. A new synthesis of substituted azulenes. Journal of the American Chemical Society, 111(1), 389-391.
328 Krishna SR, Rao BM, Rao NS.A validated rapid stability-indicating method for the determination of related substances in solifenacin succinate by ultra-fast liquid chromatography.J Chromatogr Sci. 2010 Nov;48(10):807-10.
329 Ohtake A, Sato S, Sasamata M, Miyata K.The forefront for novel therapeutic agents based on the pathophysiology of lower urinary tract dysfunction: ameliorative effect of solifenacin succinate (Vesicare), a bladder-selective antimuscarinic agent, on overactive bladder symptoms, especially urgency episodes.J Pharmacol Sci. 2010;112(2):135-41. Epub 2010 Feb 4.
330 Hoffstetter S, Leong FC.Solifenacin succinate for the treatment of overactive bladder.Expert Opin Drug Metab Toxicol. 2009 Mar;5(3):345-50.
331 Choo MS, Lee JZ, Lee JB, Kim YH, Jung HC, Lee KS, Kim JC, Seo JT, Paick JS, Kim HJ, Na YG, Lee JG.Efficacy and safety of solifenacin succinate in Korean patients with overactive bladder: a randomised, prospective, double-blind, multicentre study.Int J Clin Pract. 2008 Nov;62(11):1675-83.
332 Imamura T, et al.Combined treatment with a β3 -adrenergic receptor agonist and a muscarinic receptor antagonist inhibits detrusor overactivity induced by cold stress in spontaneously hypertensive rats. Neurourol Urodyn. 2017 Apr;36(4):1026-1033.
333 Agius L, et al. Differences between human, rat and guinea pig hepatocyte cultures. A comparative study of their rates of beta-oxidation and esterification of palmitate and their sensitivity to R-etomoxir. Biochem Pharmacol. 1991 Oct 9;42(9):1711-5.
334 O'Connor RS, et al. The CPT1a inhibitor, etomoxir induces severe oxidative stress at commonly used concentrations. Sci Rep. 2018 Apr 19;8(1):6289.
335 Bernard K, et al. DRUG FOCUS: S 18986: A positive allosteric modulator of AMPA-type glutamate receptorspharmacological profile of a novel cognitive enhancer. CNS Neurosci Ther. 2010 Oct;16(5):e193-212.
336 Bourasset F, et al. Neuropharmacokinetics of a new alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) modulator, S18986 [(S)-2,3-dihydro-[3,4]cyclopentano-1,2,4-benzothiadiazine-1,1-dioxide], in the rat. Drug Metab Dispos. 2005 Aug;33(8):1137-43.
337 Lewis HD, et al. Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation. Nat Chem Biol. 2015 Mar;11(3):189-91.
338 Cedervall J, et al. Pharmacological targeting of peptidylarginine deiminase 4 prevents cancer-associated kidney injury in mice. Oncoimmunology. 2017 Apr 20;6(8):e1320009.
339 Liu L, et al. Antiarthritis effect of a novel Bruton's tyrosine kinase (BTK) inhibitor in rat collagen-induced arthritis and mechanism-based pharmacokinetic/pharmacodynamic modeling: relationships between inhibition of BTK phosphorylation and efficacy. J
340 Sodhi JK, et al. A novel reaction mediated by human aldehyde oxidase: amide hydrolysis of GDC-0834. Drug Metab Dispos. 2015 Jun;43(6):908-15
341 Colombo M, et al. Synthesis and biological evaluation of 9-oxo-9H-indeno[1,2-b]pyrazine-2,3-dicarbonitrile analogues as potential inhibitors of deubiquitinating enzymes. ChemMedChem. 2010 Apr 6;5(4):552-8.
342 Fiorucci S, et al. Protective effects of 6-ethyl chenodeoxycholic acid, a farnesoid X receptor ligand, in estrogen-induced cholestasis. J Pharmacol Exp Ther. 2005 May;313(2):604-12.
343 Ghebremariam YT, et al. FXR agonist INT-747 upregulates DDAH expression and enhances sensitivity in high-salt fed Dahl rats. PLoS One. 2013 Apr 4;8(4):e60653.
344 Verbeke L, et al. The FXR Agonist Obeticholic Acid Prevents Gut Barrier Dysfunction and Bacterial Translocation in Cholestatic Rats. Am J Pathol. 2015 Feb;185(2):409-19.
345 Pellicciari R, et al. 6alpha-ethyl-chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity. J Med Chem. 2002 Aug 15;45(17):3569-72.
346 Chen X, et al. The therapeutic effect of fraxetin on ethanol-induced hepatic fibrosis by enhancing ethanol metabolism, inhibiting oxidative stress and modulating inflammatory mediators in rats. Int Immunopharmacol. 2018 Mar;56:98-104.
347 Liu G, et al. Effect of fraxetin on proliferation and apoptosis in breast cancer cells. Oncol Lett. 2017 Dec;14(6):7374-7378.
348 N Engl J Med 268:36, 92 (1963); J Antimicrob Chemother 52:837 (2003)
349 Wang Y, et al. Homoisoflavonoids and the Antioxidant Activity of Ophiopogon japonicus Root.
350 Ito Y, et al. A novel agent, methylophiopogonanone B, promotes Rho activation and tubulin depolymerization. Mol Cell Biochem. 2007 Mar;297(1-2):121-9. Epub 2006 Oct 7.
351 J Sci Food Agric 5: 597 (1954); Biochim Biophys Acta 39:462 (1960); Trends Food Sci Technol 10:199 (1999); Asia Pac J Clin Nutr 17 167 (2008)
352 Parkanyi Cyril, et al. Convenient synthesis of arylazo derivatives of quinoxaline, 1,4-benzothiazine, and 1,4-benzoxazine. From Journal of Heterocyclic Chemistry (1984), 21(2), 521-4.
353 Stachlewitz RF, et al.A-770041, a novel and selective small-molecule inhibitor of Lck, prevents heart allograft rejection.J Pharmacol Exp Ther. 2005 Oct;315(1):36-41.
354 Andrew Burchat, et al. Discovery of A-770041, a src-family selective orally active lck inhibitor that prevents organ allograft rejection Bioorganic &amp; Medicinal Chemistry Letters Volume 16, Issue 1, 1 January 2006, Pages 118-122
355 Kojima S, et al. Molecular basis for the maintenance of envelope integrity in Selenomonas ruminantium:cadaverine biosynthesis and covalent modification into the peptidoglycan play a major role. J Nutr Sci Vitaminol (Tokyo). 2012;58(3):153-60.
356 Dela Vega AL, et al. Polyamines decrease Escherichia coli outer membrane permeability.
357 Harada H, et al. Antitumor activity of palmitic acid found as a selective cytotoxic substance in a marine red alga. Anticancer Res. 2002 Sep-Oct;22(5):2587-90.
358 https://clinicaltrials.gov/ct2/show/NCT04542408?term=Edoxaban&cond=Covid19&draw=2&rank=1 https://clinicaltrials.gov/ct2/show/NCT04516941?term=Edoxaban&cond=Covid19&draw=2&rank=2 https://trialsearch.who.int/Trial2.aspx?TrialID=EUCTR2020-002234-32-IT
359 Naturwissenschaften 64:535 (1977); Carbohydr Res 128:235 (1984); Drugs 35:214 (1988)
360 Liu, Jing, "Synthesis of Resveratrol and Its Analogs, Phase-Transfer Catalyzed Asymmetric Glycolate Aldol Reaction, and Total Synthesis of 8,9-Methylamido-Geldanamycin" (2007). All Theses and Dissertations. 1415.
361 Br J Pharmacol 59:373 (1977); Neuropharmacology 17:13 (1978)
362 Zabkiewicz J, et al. The targeted histone deacetylase inhibitor tefinostat (CHR-2845) shows selective in vitro efficacy in monocytoid-lineage leukaemias. Oncotarget. 2016 Mar 29;7(13):16650-62.
363 Drugs (1975), 9(6), 406-23; Chemotherapy (1972), 17(6), 392-404; J. Med. Chem. (1969), 12(5), 784-91
364 Arch Derm 72:153 (1955); Artificial Cells Blood Substitutes Biotechnol 16:771 (1988)
365 J Pharmacol Exp Therap 132:295 (1961); JAMA 185:69 (1963)
366 Frank C. Dorsey, et al. Abstract 5245: Identification and characterization of the IDO1 inhibitor LY3381916. Cancer Research. 2018, 78(13).
367 Jolie Anne Bastian, et al. 1-tetrahydropyranylcarbonyl-2,3-dihydro-1h-indole compounds for treating cancer. WO2017213919A1.
368 Am J Med Sci 111:213 (1896); JAMA XXVII:728 (1896)
369 Cho YS, et al. Ginsenoside rg2 inhibits lipopolysaccharide-induced adhesion molecule expression in human umbilical vein endothelial cell. Korean J Physiol Pharmacol. 2013 Apr;17(2):133-7.
370 Li N, et al. A UPLC/MS-based metabolomics investigation of the protective effect of ginsenosides Rg1 and Rg2 in mice with Alzheimer's disease. J Ginseng Res. 2016 Jan;40(1):9-17.
371 J Chem Soc 1963:980; Tetrahedron 24: 1489 (1968); J Chem Ecology 25:923 (1999)
372 https://clinicaltrials.gov/ct2/show/NCT04420741?term=Iloprost&cond=covid&draw=2&rank=1
373 Cancer Treat Rev23:35 (1997); Exp Rev Anticancer Ther 1:13 (2001)
374 Blackburn TP, et al. The acute and chronic administration of the 5-HT(2B/2C) receptor antagonist SB-200646A significantly alters the activity of spontaneously active midbrain dopamine neurons in the rat: An in vivo extracellular single cell study. Synapse. 2006 Jun 15;59(8):502-12.
375 Kennett GA, et al. In vivo properties of SB 200646A, a 5-HT2C/2B receptor antagonist. Br J Pharmacol. 1994 Mar;111(3):797-802.
376 Theile JW, et al. Role of 5-hydroxytryptamine2C receptors in Ca2+-dependent ethanol potentiation of GABA release onto ventral tegmental area dopamine neurons. J Pharmacol Exp Ther. 2009 May;329(2):625-33.
377 Quadri L, et al. 17 beta-(3-furyl)-5 beta-androstane-3 beta, 14 beta, 17 alpha-triol (PST 2238). A very potent antihypertensive agent with a novel mechanism of action. J Med Chem. 1997 May 23;40(11):1561-4.
378 Ferrari P, et al. PST 2238: A new antihypertensive compound that modulates Na,K-ATPase in genetic hypertension. J Pharmacol Exp Ther. 1999 Mar;288(3):1074-83.
379 Matthias Lingemann, et al. The alpha-1 subunit of the Na&lt;sup&gt;+&lt;/sup&gt;,K&lt;sup&gt;+&lt;/sup&gt;-ATPase (ATP1A1) is required for macropinocytic entry of respiratory syncytial virus (RSV) in human respiratory epithelial cells. PLoS Pathog. 2019 Aug 5;15(8):e1007963.
380 Camilla F Wenceslau, et al. Rostafuroxin ameliorates endothelial dysfunction and oxidative stress in resistance arteries from deoxycorticosterone acetate-salt hypertensive rats: the role of Na&lt;sup&gt;+&lt;/sup&gt;,K&lt;sup&gt;+&lt;/sup&gt;-ATPase/cSRC pathway. J Hypertens. 2014 Mar;32(3):542-54.
381 Pharmaceut Chem J 11:60 (1977)
382 Fraser GL, et al. The NK3 Receptor Antagonist ESN364 Interrupts Pulsatile LH Secretion and Moderates Levels of Ovarian Hormones Throughout the Menstrual Cycle. Endocrinology. 2015 Nov;156(11):4214-25.
383 1,4-benzodiazepines as inhibitors of respiratory syncytial virus. The identification of a clinical candidate.
384 Gadd MS, et al. Structural basis of PROTAC cooperative recognition for selective protein degradation. Nat Chem Biol. 2017 May;13(5):514-521.
385 Lombardi MS, et al. SIK inhibition in human myeloid cells modulates TLR and IL-1R signaling and induces an anti-inflammatory phenotype. J Leukoc Biol. 2016 May;99(5):711-21.
386 Zhou J, et al. A Novel Compound ARN-3236 Inhibits Salt-Inducible Kinase 2 and Sensitizes Ovarian Cancer Cell Lines and Xenografts. Clin Cancer Res. 2017 Apr 15;23(8):1945-1954.
387 https://clinicaltrials.gov/ct2/show/NCT04363060?term=Amoxicillin&cond=covid&draw=2&rank=1
388 Mao G,et al. Bruceine D Isolated from Brucea Javanica (L.) Merr. as a Systemic Feeding Deterrent for Three Major Lepidopteran Pests. J Agric Food Chem. 2019 Apr 17;67(15):4232-4239.
389 Cheng Z, et al. Bruceine D inhibits hepatocellular carcinoma growth by targeting β-catenin/jagged1 pathways. Cancer Lett. 2017 Sep 10;403:195-205.
390 https://clinicaltrials.gov/ct2/show/NCT04622891?term=Clarithromycin&cond=COVID-19&draw=2&rank=1 https://clinicaltrials.gov/ct2/show/NCT04398004?term=Clarithromycin&cond=COVID-19&draw=2&rank=2 https://trialsearch.who.int/Trial2.aspx?TrialID=JPRN-jRCTs071210011 https://trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2020/11/029305 https://trialsearch.who.int/Trial2.aspx?TrialID=EUCTR2020-001882-36-GR
391 Zhang C, et al. Comparison of the Pharmacological Profiles of Selective PDE4B and PDE4D Inhibitors in the Central Nervous System. Sci Rep. 2017 Jan 5;7:40115.
392 J Chem Soc 1927:2489; J Biol Chem 255:7941 (1980); 259:2675 (1984); J Pharmacol Exp Ther 218:509 (1981)
393 Hatcher JM, et al. SRPKIN-1: A Covalent SRPK1/2 Inhibitor that Potently Converts VEGF from Pro-angiogenic to Anti-angiogenic Isoform. Cell Chem Biol. 2018 Apr 19;25(4):460-470.e6.
394 Fong TM, et al. Antiobesity Efficacy of a Novel Cannabinoid-1 Receptor Inverse Agonist, N-[(1S,2S)-3-(4-Chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-2&#x0D; -methyl-2-{[5-(trifluoromethyl)pyridin-2-yl]oxy}propanamide (MK-0364), in Rodents. J Pharmacol Exp T
395 Lin LS, et al. Discovery of N-[(1S,2S)-3-(4-Chlorophenyl)-2- (3-cyanophenyl)-1-methylpropyl]-2-methyl-2- {[5-(trifluoromethyl)pyridin-2-yl]oxy}propanamide (MK-0364), a novel, acyclic cannabinoid-1 receptor inverse agonist for the treatment of obesity. J M
396 Tavolari S, et al. Licofelone, a dual COX/5-LOX inhibitor, induces apoptosis in HCA-7 colon cancer cells through the mitochondrial pathway independently from its ability to affect the arachidonic acid cascade. Carcinogenesis. 2008 Feb;29(2):371-80.
397 Alvaro-Gracia JM, et al. Licofelone--clinical update on a novel LOX/COX inhibitor for the treatment of osteoarthritis. Rheumatology (Oxford). 2004 Feb;43 Suppl 1:i21-5.
398 Laufer SA, et al. (6,7-Diaryldihydropyrrolizin-5-yl)acetic acids, a novel class of potent dual inhibitors of both cyclooxygenase and 5-lipoxygenase. J Med Chem. 1994 Jun 10;37(12):1894-7.
399 Yu T, et al. Discovery of Pyridopyrimidinones as Potent and Orally Active Dual Inhibitors of PI3K/mTOR. ACS Med Chem Lett. 2018 Feb 27;9(3):256-261.
400 Sakanyan V, et al. Activation of EGFR by small compounds through coupling the generation of hydrogen peroxide to stable dimerization of Cu/Zn SOD1. Sci Rep. 2016 Feb 17;6:21088.
401 Xie F, et al. Identification, synthesis and evaluation of substituted benzofurazans as inhibitors of CREB-mediated gene transcription. Bioorg Med Chem Lett. 2013 Oct 1;23(19):5371-5.
402 Wang WY, et al. Synthesis and pharmacological evaluation of novel beta-nitrostyrene derivatives as tyrosine kinase inhibitors with potent antiplatelet activity. Biochem Pharmacol. 2007;74(4):601-611.
403 Wang WY, et al. Prevention of platelet glycoprotein IIb/IIIa activation by 3,4-methylenedioxy-beta-nitrostyrene, a novel tyrosine kinase inhibitor. Mol Pharmacol. 2006;70(4):1380-1389.
404 Life Sci. (1981), 29(12), 1271-5; Life Sci. (1964), 3, 695-702; Am. J. Cardiol. (1964), 13, 10-4
405 Everaerts W et al. Inhibition of the cation channel TRPV4 improves bladder function in mice and rats with cyclophosphamide-induced cystitis.Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):19084-9.
406 Xing Y, et al. Decreased Expression of TRPV4 Channels in HEI-OC1 Cells Induced by High Glucose Is Associated with Hearing Impairment. Yonsei Med J. 2018 Nov;59(9):1131-1137.
407 Lain S, et al. Discovery, in vivo activity, and mechanism of action of a small-molecule p53 activator. Cancer Cell. 2008;13(5):454-463.
408 Ladds MJGW, et al. Exploitation of DHODH and p53 activation as therapeutic targets - a case study in polypharmacology [published online ahead of print, 2020 Sep 8]. J Biol Chem. 2020;jbc.RA119.012056.
409 Marx C, et al. The sirtuin 1/2 inhibitor tenovin-1 induces a nonlinear apoptosis-inducing factor-dependent cell death in a p53 null Ewing's sarcoma cell line. Invest New Drugs. 2017 Nov 18.
410 Grbesa I, et al. Expression of sirtuin 1 and 2 is associated with poor prognosis in non-small cell lung cancer patients. PLoS One. 2015 Apr 27;10(4):e0124670.
411 Yoon KB, et al. Induction of Nuclear Enlargement and Senescence by Sirtuin Inhibitors in Glioblastoma Cells. Immune Netw. 2016 Jun;16(3):183-8.
412 Eur J Pharmacol 310:115 (1996); TIPS 18:204 (1997)
413 Lankas GR, et al. Dipeptidyl peptidase IV inhibition for the treatment of type 2 diabetes: potential importance of selectivity over dipeptidyl peptidases 8 and 9. Diabetes. 2005 Oct;54(10):2988-94.
414 Connolly BA, et al. Dipeptide boronic acid inhibitors of dipeptidyl peptidase IV: determinants of potencyand in vivo efficacy and safety. J Med Chem. 2008 Oct 9;51(19):6005-13.
415 Talabostat
416 Adams S, et al. PT-100, a small molecule dipeptidyl peptidase inhibitor, has potent antitumor effects and augments antibody-mediated cytotoxicity via a novel immune mechanism. Cancer Res. 2004 Aug 1;64(15):5471-80.
417 Cancer Res 35:1756 (1975); 38:2549 (1978); Clin Pharmokinet 12:223 (1987); Anal Profiles Drug Subs 19:575 (1990)|
418 Attia SM, et al. Molecular cytogenetic evaluation of the aneugenic effects of teniposide in somatic and germinal cells of male mice. Mutagenesis. 2012 Jan;27(1):31-9.
419 Li J, et al. Topoisomerase II trapping agent teniposide induces apoptosis and G2/M or S phase arrest of oral squamous cell carcinoma. World J Surg Oncol. 2006 Jul 6;4:41.
420 Sun YC, et al. MiR-181b sensitizes glioma cells to teniposide by targeting MDM2. BMC Cancer. 2014 Aug 25;14:611.
421 Roh JH, et al. Purification, characterization, and crystallization of monoamine oxidase from Escherichia coli K-12. Biosci Biotechnol Biochem. 1994 Sep;58(9):1652-6.
422 https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=Methylprednisolone&cntry=&state=&city=&dist=
423 Z Rao, et al. Study on the Synthesis of Cytarabine Hydrochloride and its Intermediate Ancitabine Hydrochloride. Fine Chemical Intermediates, 2013
424 Stebbins JL et al. Identification of a new JNK inhibitor targeting the JNK-JIP interaction site. Proc Natl Acad Sci U S A, 2008 Oct 28, 105(43):16809-13.
425 Boichot E, et al. Anti-inflammatory activities of a new series of selective phosphodiesterase 4 inhibitors derivedfrom 9-benzyladenine. J Pharmacol Exp Ther. 2000 Feb;292(2):647-53.
426 Nghiem, P., G. Pearson, and R.G. Langley, Tacrolimus and pimecrolimus: from clever prokaryotes to inhibiting calcineurin and treating atopic dermatitis. J Am Acad Dermatol, 2002. 46(2): p. 228-41.
427 Gupta, A.K. and M. Chow, Pimecrolimus: a review. J Eur Acad Dermatol Venereol, 2003. 17(5): p. 493-503.
428 Stuetz, A., M. Grassberger, and J.G. Meingassner, Pimecrolimus (Elidel, SDZ ASM 981)--preclinical pharmacologic profile and skin selectivity. Semin Cutan Med Surg, 2001. 20(4): p. 233-41.
429 J Biochem (Tokyo) 54:25, 173, 412 (1963); J Chem Soc 1964:4107
430 Crane EK, et al. Nutlin-3a: A Potential Therapeutic Opportunity for TP53 Wild-Type Ovarian Carcinomas. PLoS One. 2015 Aug 6;10(8):e0135101.
431 Tovar C, et al. Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy. Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1888-93.
432 M Ulrich, et al. Murine tumor models for the in vivo evaluation of natural compounds and their derivatives as new cancer therapeutics. München. 2016.
433 J Physiol 82:432 (1934); Phytochemistry 11:2547 (1972)
434 https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=Dexamethasone&cntry=&state=&city=&dist=
435 Wada T, et al. Prevents podocyte apoptosis induced by puromycin aminonucleoside: role of p53 and Bcl-2-related family proteins. J Am Soc Nephrol. 2005 Sep;16(9):2615-25.
436 Xia L, et al. Podocyte-specific expression of organic cation transporter PMAT: implication in puromycin aminonucleosidenephrotoxicity. Am J Physiol Renal Physiol. 2009 Jun;296(6):F1307-13.
437 Kawakami H, et al. Dynamics of absolute amount of nephrin in a single podocyte in puromycin aminonucleoside nephrosis rats calculated by quantitative glomerular proteomics approach with selected reaction monitoring mode. Nephrol Dial Transplant. 2012 Apr;
438 Nosaka K, et al. An adenosine deaminase inhibitor prevents puromycin aminonucleoside nephrotoxicity. Free Radic Biol Med 1997 ;22 (4): 597-605.
439 Lacalle RA, et al. Cloning of the complete biosynthetic gene cluster for an aminonucleoside antibiotic, puromycin, and its regulated expression in heterologous hosts. EMBO J. 1992 Feb;11(2):785-92.
440 Gong W, et al. Estrogen-related receptor-α mediates puromycin aminonucleoside-induced mesangial cell apoptosis and inflammatory injury. Am J Physiol Renal Physiol. 2019 May 1;316(5):F906-F913.
441 Sdelci S, et al. Mapping the chemical chromatin reactivation landscape identifies BRD4-TAF1 cross-talk. Nat Chem Biol. 2016 Jul;12(7):504-10.
442 Zhao Yizhaiteng, et al. Isoxazole derivative as mutated isocitrate dehydrogenase 1 inhibitor. WO2016052697A1.
443 Matsumoto K, et al. Structural basis of inhibition of cysteine proteases by E-64 and its derivatives. Biopolymers. 1999;51(1):99-107.
444 Wadhawan M, et al. Inhibition of cathepsin B by E-64 induces oxidative stress and apoptosis in filarial parasite. PLoS One. 2014 Mar 25;9(3):e93161.
445 Baldzizhar R, et al. Anti-serpin antibody-mediated regulation of proteases in autoimmune diabetes. J Biol Chem. 2013 Jan 18;288(3):1612-9.
446 Blass G, et al. Chronic cathepsin inhibition by E-64 in Dahl salt-sensitive rats. Physiol Rep. 2016 Sep;4(17). pii: e12950.
447 Hong J, et al. D-ribose induces nephropathy through RAGE-dependent NF-κB inflammation. Arch Pharm Res. 2018 Aug;41(8):838-847.
448 http://en.wikipedia.org/wiki/Roxithromycin |Antimicrob Agents Chemother 24:209 (1983); 31:1147 (1987); J Antimicrob Chemother 20 Suppl B:1 (1987)
449 Mitsuo Miyazawa, t al. Volatile components of the Rhizomes of Rheum palmatum L.Flavour and Fragrance Journal. 1996 Jan.
450 Am. J. Med. (1985), 79(4B), 12-6; Agents Actions (1976), 6(6), 748-54; Agents Actions (1975), 5(3), 256-63
451 Hao J, Synthesis and Pharmacological Characterization of 2-(2,6-Dichlorophenyl)-1-((1S,3R)-5-(3-hydroxy-3-methylbutyl)-3-(hydroxymethyl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl)ethan-1-one (LY3154207), a Potent, Subtype Selective, and Orally Available Positive Allosteric Modulator of the Human Dopamine D1 Receptor. J Med Chem. 2019 Oct 10;62(19):8711-8732.
452 J Biol Chem 138:21, 513, 529 (1041); 142:941 (1942)
453 J Am Chem Soc 89: 5737 (1967)
454 Kwon D, et al. Effects of IY-81149, a newly developed proton pump inhibitor, on gastric acid secretion in vitro and in vivo. Arzneimittelforschung. 2001;51(3):204-13.
455 Zheng M, et al. Proton pump inhibitor ilaprazole suppresses cancer growth by targeting T-cell-originated protein kinase. Oncotarget. 2017;8(24):39143-39153.
456 JACS 57: 1111 (1935); 79: 5550 (1957); Chem Rev 67: 441 (1967)
457 J. Clin. Pharm. Ther. (1991), 16(1), 41-4; Cancer Biol. Ther. (2011), 11(3), 368-370
458 Victoria Jackson-Patel, et al. Hypoxia tumour targeting with Tarloxotinib to improve clinical outcomes for patients with EGFR-dependent malignancies.
459 Parinuch Chumkaew, et al. Potent Cytotoxic Rocaglamide Derivatives From the Fruits of Amoora Cucullata. Chem Pharm Bull (Tokyo). 2006 Sep;54(9):1344-6.
460 California Med 104:363 (1966); Equine Vet J 5:162 (1973)
461 Chem Ind 1961:1037
462 https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=Voclosporin&cntry=&state=&city=&dist=&Search=Search
463 Woodhead AJ, et al. Discovery of (2,4-dihydroxy-5-isopropylphenyl)-[5-(4-methylpiperazin-1-ylmethyl)-1,3-dihydroisoindol-2-yl]methanone (AT13387), a novel inhibitor of the molecular chaperone Hsp90 by fragment based drug design. J Med Chem. 2010 Aug 26;53(16):5956-69.
464 Kang MH, et al. Initial testing (Stage 1) of AT13387, an HSP90 inhibitor, by the pediatric preclinical testing program. Pediatr Blood Cancer. 2012 Jul 15;59(1):185-8.
465 He Y, et al. The EED protein-protein interaction inhibitor A-395 inactivates the PRC2 complex. Nat Chem Biol. 2017 Apr;13(4):389-395.
466 J Antimicrob Chemother14:105 (1984); Obstet Gynecol 64:530 (1984)
467 Pruniaux MP, et al. Relationship between phosphodiesterase type 4 inhibition and anti-inflammatory activity of CI-1044 in rat airways. Fundam Clin Pharmacol. 2010 Feb;24(1):73-82.
468 https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=Estradiol&cntry=&state=&city=&dist=
469 Ring DB, et al. Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo. Diabetes. 2003 Mar;52(3):588-95.
470 Naujok O, et al. Cytotoxicity and activation of the Wnt/beta-catenin pathway in mouse embryonic stem cells treated with four GSK3 inhibitors. BMC Res Notes. 2014 Apr 29;7:273.
471 Zajkowski T, et al. Stabilization of microtubular cytoskeleton protects neurons from toxicity of N-terminal fragment of cytosolic prion protein. Biochim Biophys Acta. 2015 Oct;1853(10 Pt A):2228-39.
472 https://clinicaltrials.gov/ct2/show/NCT04770740?term=Vitamin+K1&cond=COVID-19&draw=2&rank=1 https://clinicaltrials.gov/ct2/show/NCT04780061?term=Vitamin+K1&cond=COVID-19&draw=2&rank=2
473 Eur J Dermatology 14:96 (2004); Dermatology 209: (2004); Bioorganic & Med Chem Lttrs 18:1359 (2008)
474 Chem Pharm Bull39:2906 (1991); Dig Dis Sci 43:35S (1998)
475 Fundam Appl Toxicol 7:299 (1986); Pharmacotherapy 7:25 (1987)
476 Kwiatkowski J, et al. Fragment-based Discovery of a Small-Molecule Protein Kinase C-iota Inhibitor Binding Post-kinase Domain Residues. ACS Med Chem Lett. 2019 Feb 15;10(3):318-323.
477 Nature 330:746 (1987); Semin Oncol 22 Suppl 10:1 (1995)
478 Cancer Treat Rev 17:233, 243 (1990); N Engl J Med 347:1739 (2002)
479 Freddy Radtke, et al. Inhibitors of notch signalling pathway and use thereof in treatment of cancers. US9296682B2.
480 R.Lehal, et al. Development of a novel first-in-class oral inhibitor of the NOTCH pathway.
481 Rajwinder Lehal, et al. Non clinical pharmacology, pharmacokinetics and safety profiling of CB-103: A novel first-in-class small molecule inhibitor of the NOTCH pathway.
482 Jose Manuel Perez Garcia, et al. First-in-human phase 1-2A study of CB-103, an oral Protein-Protein Interaction Inhibitor targeting pan-NOTCH signalling in advanced solid tumors and blood malignancies.
483 Silberstein SD, et al.&#x0D; Tonabersat, a gap-junction modulator: efficacy and safety in two randomized, placebo-controlled, dose-ranging studies of acute migraine.&#x0D; Cephalalgia. 2009 Nov;29 Suppl 2:17-27.
484 Chen Q, et al. Carcinoma-astrocyte gap junctions promote brain metastasis by cGAMP transfer. Nature. 2016 May 18;533(7604):493-8.
485 Kim Y, et al. Tonabersat Prevents Inflammatory Damage in the Central Nervous System by Blocking Connexin43 Hemichannels. Neurotherapeutics. 2017 May 30.
486 Coxon CR, et al. Cyclin-Dependent Kinase (CDK) Inhibitors: Structure-Activity Relationships and Insights into the CDK-2 Selectivity of 6-Substituted 2-Arylaminopurines. J Med Chem. 2017 Mar 9;60(5):1746-1767.
487 Roecker AJ et al. Discovery of 5''-chloro-N-[(5,6-dimethoxypyridin-2-yl)methyl]-2,2':5',3''-terpyridine-3'-carboxamide (MK-1064): a selective orexin 2 receptor antagonist (2-SORA) for the treatment of insomnia. ChemMedChem. 2014 Feb;9(2):311-22.
488 Gotter AL et al. Orexin 2 Receptor Antagonism is Sufficient to Promote NREM and REM Sleep from Mouse to Man. Sci Rep. 2016 Jun 3;6:27147.
489 https://clinicaltrials.gov/ct2/show/NCT04635605?term=METHYLENE+BLUE&cond=covid&draw=2&rank=7
490 Ohrui H, et al. 2'-deoxy-4'-C-ethynyl-2-fluoroadenosine, a nucleoside reverse transcriptase inhibitor, is highly potent against all human immunodeficiency viruses type 1 and has low toxicity. Chem Rec. 2006;6(3):133-43.
491 J Chem Soc 1954: 3651
492 VanArsdale T, et al. Molecular Pathways: Targeting the Cyclin D-CDK4/6 Axis for Cancer Treatment. Clin Cancer Res. 2015 Jul 1;21(13):2905-10.
493 Rader J, et al. Dual CDK4/CDK6 Inhibition Induces Cell-Cycle Arrest and Senescence in Neuroblastoma. Clin Cancer Res. 2013 Nov 15;19(22):6173-82.
494 https://clinicaltrials.gov/ct2/show/NCT04590586?term=Apremilast&cond=covid&draw=2&rank=1
495 Helv Chim Acta 33: 313 (1950)|
496 Rama Reddy NR, et al. Next Generation Sequencing and Transcriptome Analysis Predicts Biosynthetic Pathway of Sennosides from Senna (&lt;i&gt;Cassia angustifolia&lt;/i&gt; Vahl.), a Non-Model Plant with Potent Laxative Properties. PLoS One. 2015 Jun 22;10(6):e0129422.
497 Esposito F, et al. Sennoside A, derived from the traditional chinese medicine plant &lt;i&gt;Rheum L.&lt;/i&gt;, is a new dual HIV-1 inhibitor effective on HIV-1 replication. Phytomedicine. 2016 Nov 15;23(12):1383-1391.
498 Ostrem JM, et al. K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions. Nature. 2013 Nov 28;503(7477):548-551.
499 Toxicol Appl Pharmacol 2:344 (1960)
500 Dimitri E Grigoriadis, et al. Pharmacologic Characterization of Valbenazine (NBI-98854) and Its Metabolites. J Pharmacol Exp Ther. 2017 Jun;361(3):454-461.
501 Biorg. Med. Chem. (2008), 16(20), 9101-9105; Mol. Pharmacol. (1987), 31(3), 284-93; Agents Actions (1978), 8(6), 587-605
502 Phcog Rev 3:307 (2009)|Chem Commun 1968: 1392; mp 174-176 C (blackens)
503 Narjes, F, et al. The discovery of AZD0284, an inverse agonist of the nuclear receptor RORg. American Chemical Society, 2017 Drug Design and Delivery Symposium 26 October 2017
504 Asimus S, et al. Pharmacokinetics, pharmacodynamics and safety of the inverse retinoic acid-related orphan receptor γ agonist AZD0284 [published online ahead of print, 2020 Feb 17]. Br J Clin Pharmacol. 2020;10.1111/bcp.14253.
505 Biochem J 79:48 (1961); JACS 84:3400 (1962)
506 Nishiguchi GA, et al. Design and Discovery of N-(2-Methyl-5'-morpholino-6'-((tetrahydro-2H-pyran-4-yl)oxy)-[3,3'-bipyridin]-5-yl)-3-(trifluoromethyl)benzamide (RAF709): A Potent, Selective, and Efficacious RAF Inhibitor Targeting RAS Mutant Cancers. J Med Chem. 2017 Jun 22;60(12):4869-4881.
507 Rama Reddy NR, et al. Next Generation Sequencing and Transcriptome Analysis Predicts Biosynthetic Pathway of Sennosides from Senna (&lt;i&gt;Cassia angustifolia&lt;/i&gt; Vahl.), a Non-Model Plant with Potent Laxative Properties. PLoS One. 2015 Jun 22;10(6):e0129422.
508 Chen YC, et al. Sennoside B inhibits PDGF receptor signaling and cell proliferation induced by PDGF-BB in human osteosarcoma cells. Life Sci. 2009 Jun 19;84(25-26):915-22.
509 Garcia-Jimenez A, et al. Action of tyrosinase on alpha and beta-arbutin: A kinetic study. PLoS One. 2017 May 11;12(5):e0177330.
510 Jiang L, et al. Investigation of the pro-apoptotic effects of arbutin and its acetylated derivative on murinemelanoma cells. Int J Mol Med. 2018 Feb;41(2):1048-1054.
511 Nalban N, et al. Arbutin Attenuates Isoproterenol-Induced Cardiac Hypertrophy by Inhibiting TLR-4/NF-κB Pathway in Mice. Cardiovasc Toxicol. 2019 Sep 4. |Pharmazie 15: 650 (1960); 46:611 (1991); J Pharmacol Exp Ther 276:765 (1996); Pigment Cell Res 11:12, 206 (1998)
512 Wang J, et al. Structural and Atropisomeric Factors Governing the Selectivity of Pyrimido-benzodiazipinonesas Inhibitors of Kinases and Bromodomains. ACS Chem Biol. 2018 Sep 21;13(9):2438-2448
513 J Clin Pharm Ther 27:343 (2002); Exp Opin Pharmacother 3:1211 (2002)
514 Zhang S, et al. Small-Molecule NSC59984 Restores p53 Pathway Signaling and Antitumor Effects against Colorectal Cancer via p73 Activation and Degradation of Mutant p53. Cancer Res. 2015 Sep 15;75(18):3842-52.
515 Zhang S, et al. Small-Molecule NSC59984 Restores p53 Pathway Signaling and Antitumor Effects againstColorectal Cancer via p73 Activation and Degradation of Mutant p53. Cancer Res. 2015 Sep 15;75(18):3842-52.
516 Eur J Pharmacol 179: 295 (1990)
517 https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=BETAMETHASONE&cntry=&state=&city=&dist=
518 Lan P, Romero FA, et al. Hit-to-Lead Optimization and Discovery of 5-((5-([1,1'-Biphenyl]-4-yl)-6-chloro-1H-benzo[d]imidazol-2-yl)oxy)-2-methylbenzoic Acid (MK-3903): A Novel Class of Benzimidazole-Based Activators of AMP-Activated Protein Kinase. J Med Chem. 2017 Nov 9;60(21):9040-9052.
519 Sun J, et al. Antitumor efficacy of a novel class of non-thiol-containing peptidomimetic inhibitors of farnesyltransferase and geranylgeranyltransferase I: combination therapy with the cytotoxic agents cisplatin, Taxol, and gemcitabine. Cancer Res. 1999 Oct 1;59(19):4919-26.
520 N C Crespo, et al. The farnesyltransferase inhibitor, FTI-2153, inhibits bipolar spindle formation during mitosis independently of transformation and Ras and p53 mutation status. Cell Death Differ. 2002 Jul;9(7):702-9.
521 Snyder DW, et al. Pharmacology of LY315920/S-5920, [[3-(aminooxoacetyl)-2-ethyl-1- (phenylmethyl)-1H-indol-4-yl]oxy] acetate, a potent and selective secretory phospholipase A2 inhibitor: A new class of anti-inflammatory drugs, SPI. J Pharmacol Exp Ther. 1999 Mar;288(3):1117-24.
522 Hori Y, et al. Effect of retinoic acid on gene expression in human conjunctival epithelium: secretory phospholipase A2 mediates retinoic acid induction of MUC16. Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4050-61.
523 Pharmacological reports 58:246 (2006)
524 Bishop AC, et al. A chemical switch for inhibitor-sensitive alleles of any protein kinase. Nature. 2000 Sep 21;407(6802):395-401.
525 Tandon M, et al. New pyrazolopyrimidine inhibitors of protein kinase d as potent anticancer agents for prostate cancer cells. PLoS One. 2013 Sep 23;8(9):e75601.
526 Tobacco Science 3:86 (1959); Phytochemistry 39:1383 (1995)
527 Gray NS, et al. Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors. Science. 1998 Jul 24;281(5376):533-8.
528 Bain J, et al. The specificities of protein kinase inhibitors: an update. Biochem J. 2003 Apr 1;371(Pt 1):199-204.
529 Villerbu N, et al. Cellular effects of purvalanol A: a specific inhibitor of cyclin-dependent kinase activities. Int J Cancer. 2002 Feb 20;97(6):761-9.
530 Garai S, et al. B-973, a Novel α7 nAChR Ago-PAM: Racemic and Asymmetric Synthesis, Electrophysiological Studies, and in Vivo Evaluation. ACS Med Chem Lett. 2018 Oct 11;9(11):1144-1148.
531 Jessica Chinison, et al. Triptonide Effectively Inhibits Wnt/β-Catenin Signaling via C-terminal Transactivation Domain of β-catenin. Sci Rep. 2016; 6: 32779.
532 Ping Yang, et al. Triptonide acts as a novel potent anti-lymphoma agent with low toxicity mainly through inhibition of proto-oncogene Lyn transcription and suppression of Lyn signal pathway. Toxicol LettPing Yang. 2017 Aug 15;278:9-17.
533 Souness JE, et al. Role of selective cyclic GMP phosphodiesterase inhibition in the myorelaxant actions of M&amp;B 22,948, MY-5445, vinpocetine and 1-methyl-3-isobutyl-8-(methylamino)xanthine. Br J Pharmacol. 1989 Nov;98(3):725-34.
534 Chung-Pu Wu, et al. MY-5445, a phosphodiesterase type 5 inhibitor, resensitizes ABCG2-overexpressing multidrug-resistant cancer cells to cytotoxic anticancer drugs. Am J Cancer Res. 2020; 10(1): 164–178.
535 Maud Bollenbach, et al. Design and synthesis of 3-aminophthalazine derivatives and structural analogues as PDE5 inhibitors: anti-allodynic effect against neuropathic pain in a mouse model. Eur J Med Chem. 2019 Sep 1;177:269-290.
536 Zhisong Cao, et al. Crystalline camptothecin-20(S)-O-propionate hydrate: a novel anticancer agent with strong activity against 19 human tumor xenografts. Cancer Res. 2009 Jun 1;69(11):4742-9.
537 Zhisong Cao, et al. Crystalline camptothecin-20(S)-O-propionate hydrate: a novel anticancer agent with strong activity against 19 human tumor xenografts. Cancer Res. 2009 Jun 1;69(11):4742-9.
538 Xing Liu, et al. Correlation between the sensitivity of tumors to treatment with CZ48 and local concentrations of the active metabolite CPT within the tumors. Biomed Rep. 2013 Mar;1(2):202-206.
539 Volynets GP, et al. Identification of 3H-naphtho[1,2,3-de]quinoline-2,7-diones as inhibitors of apoptosis signal-regulating kinase 1 (ASK1). J Med Chem. 2011 Apr 28;54(8):2680-6.
540 Hao H, et al. NQDI-1, an inhibitor of ASK1 attenuates acute perinatal hypoxic-ischemic cerebral injury by modulating cell death. Mol Med Rep. 2016 Jun;13(6):4585-92.
541 Zhang M, et al. Structure-Based Discovery and Optimization of Benzo[ d]isoxazole Derivatives as Potent and Selective BET Inhibitors for Potential Treatment of Castration-Resistant Prostate Cancer (CRPC). J Med Chem. 2018 Apr 12;61(7):3037-3058.
542 Peserico A, et al. A SMYD3 Small-Molecule Inhibitor Impairing Cancer Cell Growth. J Cell Physiol. 2015 Oct;230(10):2447-2460.
543 JACS 61:2832 (1939); 63:422 (1941); 68:406 (1945); J Pharm Biomed Anal 48:127 (2008)
544 Therapeut Clin Risk Man 2:3 (2006); Bone 44:423 (2009); J Gastrointestin Liver Dis 20::141 (2011)
545 https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=Ibrutinib&cntry=&state=&city=&dist=
546 Jortani SA, et al. Inhibition of Na,K-ATPase by oleandrin and oleandrigenin, and their detection by digoxin immunoassays. Clin Chem. 1996 Oct;42(10):1654-8.
547 Yang P, et al. Cellular location and expression of Na&lt;sup&gt;+&lt;/sup&gt;, K&lt;sup&gt;+&lt;/sup&gt;-ATPase α subunits affect the anti-proliferative activity of oleandrin. Mol Carcinog. 2014 Apr;53(4):253-63.
548 Garofalo S, et al. The Glycoside Oleandrin Reduces Glioma Growth with Direct and Indirect Effects on Tumor Cells. J Neurosci. 2017 Apr 5;37(14):3926-3939.
549 Shoji JH, et al. Isolation of azomycin from Pseudomonas fluorescens. J Antibiot (Tokyo). 1989 Oct;42(10):1513-4.
550 Chem Commun 1968:1395; Phytochemistry 17: 1395 (1978); Phytopathology 71:521 (1981)
551 Wang L, et al. Carnosol suppresses patient-derived gastric tumor growth by targeting RSK2. Oncotarget. 2018 Feb 6;9(76):34200-34212.
552 Li X, et al. Carnosol as a Nrf2 Activator Improves Endothelial Barrier Function Through Antioxidative Mechanisms. Int J Mol Sci. 2019;20(4):880. Published 2019 Feb 18.
553 Martin D, et al. Regulation of heme oxygenase-1 expression through the phosphatidylinositol 3-kinase/Akt pathway and the Nrf2 transcription factor in response to the antioxidant phytochemical carnosol. J Biol Chem. 2004;279(10):8919-8929.
554 J Allergy Clin Immunol 76:703 (1985)
555 Watt GD, et al. Protective effect opf lodoxamide tromethamine on allergen inhalation challenge. J Allergy Clin Immunol. 1980 Oct;66(4):286-94.
556 Capron M,et al. Inhibitory effects of lodoxamide on eosinophil activation. Int Arch Allergy Immunol. 1998 Jun;116(2):140-6.
557 Barr ML, et al. Addition of a mast cell stabilizing compound to organ preservation solutions decreases lung reperfusion injury. J Thorac Cardiovasc Surg. 1998 Mar;115(3):631-6; discussion 636-7.
558 Mann JS, et al. Inhaled lodoxamide tromethamine in the treatment of perennial asthma: a double-blind placebo-controlled study. J Allergy Clin Immunol. 1985 Jul;76(1):83-90.
559 J Med Chem 28:1558 (1985); J Antimicrob Chemother 19:611 (1987)
560 Bernard Christophe Barlaam, etal. Chemical compounds. Patent US20180111931.
561 Donghua Yin, et al. Pharmacodynamics of selective androgen receptor modulators. J Pharmacol Exp Ther. 2003 Mar;304(3):1334-40.
562 Ioannis Simitsidellis, et al. Selective androgen receptor modulators (SARMs) have specific impacts on the mouse uterus. J Endocrinol. 2019 Sep;242(3):227-239.
563 Buchanan SG, et al. SGX523 is an exquisitely selective, ATP-competitive inhibitor of the MET receptor tyrosine kinase with antitumor activity in vivo. Mol Cancer Ther, 2009, 8(12), 3181-3190.
564 Shen A, et al. c-Myc alterations confer therapeutic response and acquired resistance to c-Met inhibitors in MET-addicted cancers. Cancer Res. 2015 Nov 1;75(21):4548-59.
565 Müller J, et al. Buparvaquone is active against Neospora caninum in vitro and in experimentally infected mice. Int J Parasitol Drugs Drug Resist. 2015 Feb 13;5(1):16-25.
566 Reimão JQ, et al. Effectiveness of liposomal buparvaquone in an experimental hamster model of Leishmania (L.) infantum chagasi. Exp Parasitol. 2012 Mar;130(3):195-9.
567 Garnier T, et al. In vivo studies on the antileishmanial activity of buparvaquone and its prodrugs. J Antimicrob Chemother. 2007 Oct;60(4):802-10.
568 Carnero A. Novel inhibitors of the PI3K family. Expert Opin Investig Drugs. 2009 Sep;18(9):1265-77.
569 Maira SM, et al. From the bench to the bed side: PI3K pathway inhibitors in clinical development. Curr Top Microbiol Immunol, 2010, 347, 209-239.
570 Takashi Kei Kishimoto, et al. Methods and compositions for attenuating gene therapy anti-viral transfer vector immune responses. US 20160074531 A1.
571 Mersereau JE, et al. Liquiritigenin is a plant-derived highly selective estrogen receptor beta agonist. Mol Cell Endocrinol. 2008 Feb 13;283(1-2):49-57.
572 Suh KS, et al. Protective effect of liquiritigenin against methylglyoxal cytotoxicity in osteoblastic MC3T3-E1 cells. Food Funct. 2014 Jul 25;5(7):1432-40.
573 Tao W, et al. Liquiritigenin reverses depression-like behavior in unpredictable chronic mild stress-induced mice by regulating PI3K/Akt/mTOR mediated BDNF/TrkB pathway. Behav Brain Res. 2016 Jul 15;308:177-86.
574 Herrero A, et al. Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes. Cancer Cell. 2015 Aug 10;28(2):170-82.
575 Kato H, et al. CCK-2/gastrin receptor signaling pathway is significant for gemcitabine-induced gene expression of VEGF in pancreatic carcinoma cells. Life Sci. 2011 Oct 24;89(17-18):603-8.
576 Fukuda-Tsuru S, et al. A novel, potent, and long-lasting dipeptidyl peptidase-4 inhibitor, teneligliptin, improves postprandial hyperglycemia and dyslipidemia after single and repeated administrations. Eur J Pharmacol. 2012 Dec 5;696(1-3):194-202.
577 Ideta T, et al. The Dipeptidyl Peptidase-4 Inhibitor Teneligliptin Attenuates Hepatic Lipogenesis via AMPK Activation in Non-Alcoholic Fatty Liver Disease Model Mice. Int J Mol Sci. 2015 Dec 8;16(12):29207-18.
578 Acta Pharmacologica Toxicologica 51: 250 (1982); Brain Res 1054:45 (2005);
579 https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=HYDROXYCHLOROQUINE+&cntry=&state=&city=&dist=
580 . Tanaka H, et al. Preclinical antitumor activity of S-222611, an oral reversible tyrosine kinase inhibitor of epidermal growth factor receptor and human epidermal growth factor receptor 2. Cancer Sci. 2014 Aug;105(8):1040-8.
581 Lautenschläger M, et al. Intestinal formation of trans-Crocetin from saffron extract (&lt;i&gt;Crocus sativus L.&lt;/i&gt;) and in vitro permeation through intestinal and blood brain barrier. Phytomedicine. 2015 Jan 15;22(1):36-44.
582 https://clinicaltrials.gov/ct2/show/NCT04467931?term=PINDOLOL&cond=Covid19&draw=2&rank=1
583 https://clinicaltrials.gov/ct2/show/NCT04365257?term=PRAZOSIN&cond=covid&draw=2&rank=1
584 Messoussi A, et al. Recent progress in the design, study, and development of c-Jun N-terminal kinase inhibitors as anticanceragents. Chem Biol. 2014 Nov 20;21(11):1433-43.
585 Okada M, et al. The novel JNK inhibitor AS602801 inhibits cancer stem cells in vitro and in vivo. Oncotarget. 2016 May 10;7(19):27021-32.
586 Palmer SS, et al. Bentamapimod (JNK Inhibitor AS602801) Induces Regression of Endometriotic Lesions in Animal Models. Reprod Sci. 2016 Jan;23(1):11-23.
587 Sheila M Mitchell, et al. The effects of ponazuril on development of apicomplexans in vitro. J Eukaryot Microbiol. May-Jun 2005;52(3):231-5.
588 Sheila M Mitchell, et al. Efficacy of ponazuril in vitro and in preventing and treating Toxoplasma gondii infections in mice. J Parasitol. 2004 Jun;90(3):639-42.
589 Aust J Chem 24:2427 (1971); Phytochemistry 32:1083 (1993); J Nat Prod 58:1958 (1995)
590 Adam Becalski, et al. Semicarbazide Formation in Azodicarbonamide-Treated Flour: A Model Study. J Agric Food Chem. 2004 Sep 8;52(18):5730-4.
591 Pérez-Salvia M, et al. Bromodomain inhibitors and cancer therapy: From structures to applications. Epigenetics. 2017 May 4;12(5):323-339.
592 Phillip CC Liu, et al. Abstract 3523: Discovery of a novel BET inhibitor INCB054329.
593 Liu ZM, et al. Early investigational drugs targeting PPAR-α for the treatment of metabolic disease.Expert Opin Investig Drugs. 2015 May;24(5):611-21.
594 Ratziu V, et al. Elafibranor, an Agonist of the Peroxisome Proliferator-Activated Receptor-α and -δ, Induces Resolution of Nonalcoholic Steatohepatitis Without Fibrosis Worsening. Gastroenterology. 2016 May;150(5):1147-1159.
595 Hanf R, et al. The dual peroxisome proliferator-activated receptor alpha/delta agonist GFT505 exerts anti-diabetic effects in db/db mice without peroxisome proliferator-activated receptor gamma-associated adverse cardiac effects.Diab Vasc Dis Res. 2014 No
596 Zachary S. Zumsteg, et al. Taselisib (GDC-0032), a Potent β-Sparing Small Molecule Inhibitor of PI3K, Radiosensitizes Head and Neck Squamous Carcinomas Containing Activating PIK3CA Alterations. Clin Cancer Res. 2016 Apr 15; 22(8): 2009–2019.
597 Marian M. Deuker, et al. PI3′-Kinase Inhibition Forestalls the Onset of MEK1/2 Inhibitor Resistance in BRAF-Mutated Melanoma. Cancer Discov. 2015 Feb; 5(2): 143–153.
598 Ndubaku CO, et al. Discovery of 2-{3-[2-(1-isopropyl-3-methyl-1H-1,2-4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl]-1H-pyrazol-1-yl}-2-methylpropanamide (GDC-0032): a β-sparing phosphoinositide 3-kinase inhibitor with high unbound exposure and robust in vivo antitumor activity. J Med Chem. 2013 Jun 13;56(11):4597-610.
599 Wang JL, et al. Structure-based discovery of an organic compound that binds Bcl-2 protein and induces apoptosis of tumor cells. Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7124-9.
600 Kessel D, et al. Initiation of apoptosis and autophagy by the Bcl-2 antagonist HA14-1. Cancer Lett. 2007 May 8;249(2):294-9.
601 Manero F, et al. The small organic compound HA14-1 prevents Bcl-2 interaction with Bax to sensitize malignant glioma cells to induction of cell death. Cancer Res. 2006 Mar 1;66(5):2757-64.
602 Wong EH, et al. The anticonvulsant MK-801 is a potent N-Me-D-Asp antagonist. Proc Natl Acad Sci U S A. 1986 Sep;83(18):7104-8.
603 Vardhan Reddy KH, et al. Convergent Strategy to Dizocilpine MK-801 and Derivatives. J Org Chem. 2018 Apr 6;83(7):4264-4269.
604 Huettner JE, et al. Block of N-Me-D-Asp-activated current by the anticonvulsant MK-801: selective binding to open channels. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1307-11.
605 Thomas DM, et al. MK-801 and dextromethorphan block microglial activation and protect against neurotoxicity. Brain Res. 2005 Jul 19;1050(1-2):190-8.
606 Brown TE, et al. The NMDA antagonist MK-801 disrupts reconsolidation of a cocaine-associated memory for conditioned place preference but not for self-administration in rats. Learn Mem. 2008 Dec 2;15(12):857-65.
607 Jiang L, et al. Decrease of growth and differentiation factor 10 contributes to neuropathic pain through N-Me-D-Asp receptor activation. Neuroreport. 2017 May 24;28(8):444-450.
608 Iijima Y, et al. Modification by MK-801 (dizocilpine), a noncompetitive NMDA receptor antagonist sensitization: evaluation by ambulation in mice. Nihon Shinkei Seishin Yakurigaku Zasshi. 1996 Feb;16(1):11-8.
609 Antimicrob Agents Chemother 19:82 (1981)
610 Chem Nat Compounds 34:295 (1998); J Asian Nat Prod Res 10:1093 (2008)
611 Annika Birgitta Margareta ÅSTRAND, et al. Compounds and methods for inhibiting jak. WO2017050938A1.
612 Miller BE, et al. The pharmacokinetics and pharmacodynamics of danirixin (GSK1325756)--a selective CXCR2 antagonist?--in healthy adult subjects. BMC Pharmacol Toxicol. 2015 Jun 20;16:18.
613 Wang S, et al. Development of Highly Potent, Selective, and Cellular Active Triazolo[1,5- a]pyrimidine-Based Inhibitors Targeting the DCN1-UBC12 Protein-Protein Interaction. J Med Chem. 2019 Mar 14;62(5):2772-2797.
614 Funahashi Y, et al. Sulfonamide derivative, E7820, is a unique angiogenesis inhibitor suppressing an expression of integrin alpha2 subunit on endothelium. Cancer Res. 2002;62(21):6116-6123.
615 Ito K, et al. Enhanced anti-angiogenic effect of E7820 in combination with erlotinib in epidermal growth factor receptor-tyrosine kinase inhibitor-resistant non-small-cell lung cancer xenograft models. Cancer Sci. 2014;105(8):1023-1031.
616 Polycyclic Aromat. Compd. (2004), 24(4-5), 733-742; Mutat. Res., Genet. Toxicol. Test. (1984), 135(2), 97-103; Environ. Toxicol. Chem. (2005), 24(10), 2526-2532
617 https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=Maraviroc&cntry=&state=&city=&dist=&Search=Search
618 Arzneim Forsch 26:925 (1976)|
619 Lim KM, et al. Analysis of changes in microRNA expression profiles in response to the troxerutin-mediated antioxidant effect in human dermal papilla cells. Mol Med Rep. 2015 Aug;12(2):2650-60.
620 Zhang Z, et al. Troxerutin Attenuates Enhancement of Hepatic Gluconeogenesis by Inhibiting NOD Activation-Mediated Inflammation in High-Fat Diet-Treated Mice. Int J Mol Sci. 2016 Dec 25;18(1). pii: E31.
621 Badalzadeh R, et al. Beneficial effect of troxerutin on diabetes-induced vascular damages in rat aorta: histopathological alterations and antioxidation mechanism. Int J Endocrinol Metab. 2015 Apr 30;13(2):e25969.
622 J Neurochem 34:1247 (1980); J Neurosci18:156 (1998); J Clin Invest 122:2837 (2012)
623 Chou TF, et al.Reversible inhibitor of p97, DBeQ, impairs both ubiquitin-dependent and autophagic protein clearance pathways. Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4834-9.
624 Zhang Y, et al. The AAA ATPase Vps4 Plays Important Roles in Candida albicans Hyphal Formation and is Inhibited by DBeQ. Mycopathologia. 2016 Jun;181(5-6):329-39.
625 Davidson Alan Hornsby, et al. Preparation of amino acid-based hydroxamic acids as histone deacetylase (HDAC) inhibitors. From PCT Int. Appl. (2008), WO 2008040934 A1 20080410.
626 Cassidy-Stone A, et al. Chemical inhibition of the mitochondrial division dynamin reveals its role in Bax/Bak-dependent mitochondrial outer membrane permeabilization. Dev Cell. 2008 Feb;14(2):193-204.
627 Tanaka A, et al. A chemical inhibitor of DRP1 uncouples mitochondrial fission and apoptosis. Mol Cell. 2008 Feb 29;29(4):409-10.
628 Park SW, et al. A selective inhibitor of drp1, mdivi-1, increases retinal ganglion cell survival in acute ischemic mouse retina. Invest Ophthalmol Vis Sci. 2011 Apr 27;52(5):2837-43.
629 Iverson C, et al. RDEA119/BAY 869766: a potent, selective, allosteric inhibitor of MEK1/2 for the treatment of cancer. Cancer Res. 2009 Sep 1;69(17):6839-47.
630 Adovelande J, et al. Synergy between two calcium channel blockers, verapamil and fantofarone (SR33557), in reversing chloroquine resistance in Plasmodium falciparum. Biochem Pharmacol. 1998 Feb 15;55(4):433-40.
631 Dongay B, et al. Effect of fantofarone, a new Ca2+ channel antagonist, on angioplasty-induced vasospasm in an atherosclerotic rabbit model. Biochem Pharmacol. 1998 Jun 15;55(12):2047-50.
632 Darblade B, et al. Piboserod (SB 207266), a selective 5-HT4 receptor antagonist, reduces serotonin potentiation of neurally-mediated contractile responses of human detrusor muscle. World J Urol. 2005 Jun;23(2):147-51.
633 Kjekshus JK, et al. Effect of piboserod, a 5-HT4 serotonin receptor antagonist, on left ventricular function in patients with symptomatic heart failure. Eur J Heart Fail. 2009 Aug;11(8):771-8.
634 Nirogi R, et al. In-vivo rat striatal 5-HT4 receptor occupancy using non-radiolabelled SB207145. J Pharm Pharmacol. 2013 May;65(5):704-12.
635 Erickson-Miller CL, et al. Preclinical activity of eltrombopag (SB-497115), an oral, nonpeptide thrombopoietin receptor agonist. Stem Cells. 2009 Feb;27(2):424-30.
636 Erickson-Miller CL, et al. Discovery and characterization of a selective, nonpeptidyl thrombopoietin receptor agonist. Exp Hematol. 2005 Jan;33(1):85-93.
637 McHutchison JG, et al. Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C. N Engl J Med. 2007 Nov 29;357(22):2227-36.
638 Jenkins JM, et al. Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist. Blood. 2007 Jun 1;109(11):4739-41.
639 Saleh MN, et al. Safety and efficacy of eltrombopag for treatment of chronic immune thrombocytopenia: results of the long-term, open-label EXTEND study. Blood. 2013 Jan 17;121(3):537-45.
640 Juan Zhu, et al. Identification of Eltrombopag as a Repurposing Drug Against Staphylococcus epidermidis and its Biofilms. Curr Microbiol. 2021 Feb 21.
641 https://clinicaltrials.gov/ct2/show/NCT04834752?term=Pantoprazole&cond=Covid19&draw=2&rank=1
642 Ligat G, et al. Identification of Amino Acids Essential for Viral Replication in the HCMV Helicase-PrimaseComplex. Front Microbiol. 2018 Oct 23;9:2483.
643 Wald A, et al. Helicase-primase inhibitor Pritelivir for HSV-2 infection. N Engl J Med. 2014 Jan 16;370(3):201-10.
644 Quenelle DC, et al. Efficacy of pritelivir and acyclovir in the treatment of herpes simplex virus infections in a mouse model of herpes simplex encephalitis. Antiviral Res. 2018 Jan;149:1-6.
645 Weir HM, et al. AZD9496: An Oral Estrogen Receptor Inhibitor That Blocks the Growth of ER-Positive and ESR1-Mutant Breast Tumors in Preclinical Models. Cancer Res. 2016 Jun 1;76(11):3307-18.
646 De Savi C, et al. Optimization of a Novel Binding Motif to (E)-3-(3,5-Difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic Acid (AZD9496), a Potent and Orally Bioavailable Selective Estrogen Receptor Downregulator and Antagonist. J Med Chem. 2015 Oct 22;58(20):8128-40.
647 Pan S, et al. Discovery of NVP-LDE225, a Potent and Selective Smoothened Antagonist. ACS Med Chem Lett. 2010 Mar 16;1(3):130-4.
648 Irvine DA, et al. Deregulated hedgehog pathway signaling is inhibited by the smoothened antagonist LDE225 (Sonidegib) in chronic phase chronic myeloid leukaemia. Sci Rep. 2016 May 9;6:25476.
649 Kargl J, et al. A selective antagonist reveals a potential role of G protein-coupled receptor 55 in platelet and endothelial cell function.&#x0D; J Pharmacol Exp Ther. 2013 Jul;346(1):54-66.
650 Acta Pharmacol Toxicol 47:17 (1980)
651 Moradi-Afrapoli F, et al. Cinnamoylphenethyl amides from Polygonum hyrcanicum possess anti-trypanosomal activity. Nat Prod Commun. 2012 Jun;7(6):753-5.
652 Kim DK, et al. Inhibitory effect of trans-N-p-coumaroyl tryamine from the twigs of Celtis chinensis on the acetylcholinesterase. Arch Pharm Res. 2003 Sep;26(9):735-8.
653 Inhibition of IκB kinase-β protects dopamine neurons against lipopolysaccharide-induced neurotoxicity By Zhang, Feng; Qian, Li; Flood, Patrick M.; Shi, Jing-Shan; Hong, Jau-Shyong; Gao, Hui-Ming J Pharmacol Exp Ther. 2010 June; 333(3): 822-833.
654 Cooper MJ, et al. Application of multiplexed kinase inhibitor beads to study kinome adaptations in drug-resistant leukemia. PLoS One. 2013 Jun 24;8(6):e66755.
655 Schneeweiss M, et al. The KIT and PDGFRA switch-control inhibitor DCC-2618 blocks growth and survival of multiple neoplastic cell types in advanced mastocytosis. Haematologica. 2018 May;103(5):799-809.
656 KIT/PDGFR Inhibitor DCC-2618.
657 Schneeweiss M, et al. The KIT and PDGFRA switch-control inhibitor DCC-2618 blocks growth and survival of multiple neoplastic cell types in advanced mastocytosis. Haematologica. 2018 May;103(5):799-809.
658 BLU-285, DCC-2618 Show Activity against GIST. Cancer Discov. 2017 Feb;7(2):121-122.
659 Stover CK, et al. A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis. Nature. 2000 Jun 22;405(6789):962-6.
660 Lenaerts AJ, et al. Preclinical testing of the nitroimidazopyran PA-824 for activity against Mycobacterium tuberculosis in a series of in vitro and in vivo models. Antimicrob Agents Chemother. 2005 Jun;49(6):2294-301.
661 Manjunatha UH, et al. Mycobacterium leprae is naturally resistant to PA-824. Antimicrob Agents Chemother. 2006 Oct;50(10):3350-4.
662 Arzneim Forsch 17:523, 526, 534 (1967); 21:1907 (1971)
663 Linyan Xu, et al. Cladribine Induces ATF4 Mediated Apoptosis and Synergizes with SAHA in Diffuse Large B-Cell Lymphoma Cells. Int J Med Sci. 2020; 17(10): 1375–1384.
664 Jian Ma, et al. Therapeutic potential of cladribine in combination with STAT3 inhibitor against multiple myeloma. BMC Cancer. 2011 Jun 16;11:255.
665 Young Seop Chang, et al. MP28-10 COMBINED EFFECTS OF MELATONIN AND CLADRIBINE ON APOPTOSIS IN ISCHEMIA/REPERFUSION INJURY IN RAT BLADDER. THE JOURNAL OF UROLOGY. April 2016. 195 (4S): e375.
666 Crystal D Hayes, et al. Chronic cladribine administration increases amyloid beta peptide generation and plaque burden in mice. PLoS One. 2012;7(10):e45841.
667 Yeung, P. K. F., et al. Pharmacokinetics of Cladribine in a Rat Model Following Subcutaneous and Intra-arterial Injections. Drug Metabol Drug Interact. 2008;23(3-4):291-8.
668 Zengerle M, et al. Selective Small Molecule Induced Degradation of the BET Bromodomain Protein BRD4. ACS Chem Biol. 2015;10(8):1770‐1777.
669 Minna Bui, et al. Heteroaryl btk inhibitors. WO2011029043A1
670 McAfee Q, et al. Autophagy inhibitor Lys05 has single-agent antitumor activity and reproduces the phenotype of a genetic autophagy deficiency. Proc Natl Acad Sci U S A. 2012 May 22;109(21):8253-8.
671 Shih C, et al. LY231514, a pyrrolo[2,3-d]pyrimidine-based antifolate that inhibits multiple folate-requiring enzymes. Cancer Res. 1997 Mar 15;57(6):1116-23.
672 Anraku M, et al. Synergistic antitumor effects of regulatory T cell blockade combined with pemetrexed in murine malignantmesothelioma. J Immunol. 2010 Jul 15;185(2):956-66.
673 Bai L, et al. A Potent and Selective Small-Molecule Degrader of STAT3 Achieves Complete Tumor Regression In Vivo. Cancer Cell. 2019 Nov 11;36(5):498-511.e17.
674 Zhou B, et al. Discovery of a Small-Molecule Degrader of Bromodomain and Extra-Terminal (BET) Proteins with Picomolar Cellular Potencies and Capable of Achieving Tumor Regression. J Med Chem. 2018 Jan 25;61(2):462-481.
675 Liewen MB, et al. Growth and Inhibition of Microorganisms in the Presence of Sorbic Acid: A Review. J Food Prot. 1985 Apr;48(4):364-375.
676 Pu W, et al. Targeting Pin1 by inhibitor API-1 regulates microRNA biogenesis and suppresses hepatocellularcarcinoma development. Hepatology. 2018 Aug;68(2):547-560.
677 Lenta BN, et al. Leishmanicidal and cholinesterase inhibiting activities of phenolic compounds from Allanblackia monticola and Symphonia globulifera. Molecules. 2007 Jul 20;12(8):1548-57.
678 Ciochina R, et al. Polycyclic polyprenylated acylphloroglucinols. Chem Rev. 2006 Sep;106(9):3963-86.
679 Li F, et al. Garcinol, a polyisoprenylated benzophenone modulates multiple proinflammatory signalingcascades leading to the suppression of growth and survival of head and neck carcinoma. Cancer Prev Res (Phila). 2013 Aug;6(8):843-54.
680 Drugs 15:409 (1978); Am J Cardiol 57:1H (1986); N Engl J Med 337:365 (1997): Circulation 105:2549 (2002).
681 Saalau-Bethell SM, et al. Discovery of an allosteric mechanism for the regulation of HCV NS3 protein function. Nat Chem Biol. 2012 Nov;8(11):920-5.
682 Boolbol SK, et al. Cyclooxygenase-2 overexpression and tumor formation are blocked by sulindac in a murine model of familial adenomatous polyposis. Cancer Res. 1996 Jun 1;56(11):2556-60.
683 Gong EY, et al. Combined treatment with vitamin C and sulindac synergistically induces p53- and ROS-dependent apoptosis in human colon cancer cells. Toxicol Lett. 2016 Sep 6;258:126-133.
684 Cha BK, et al. Celecoxib and sulindac inhibit TGF-β1-induced epithelial-mesenchymal transition and suppress lung cancer migration and invasion via downregulation of sirtuin 1. Oncotarget. 2016 Aug 30;7(35):57213-57227. |Drugs 16:97 (1978); Dig Dis 12:259 (1994)
685 J Antimicrob Chemother 10:Suppl B:1 (1982); Drugs 32 Suppl 3:1 (1986)
686 J Biol Chem 202:801 (1953); Photochem Photobiol 39:851 (1984); 55:145 (1992)
687 Appl Microbiol 22:480 (1971); J Vet Intern Med 20:536 (2006)|
688 Jody L Gookin, et al. Efficacy of ronidazole for treatment of feline Tritrichomonas foetus infection. J Vet Intern Med
689 Kirkin V, et al. Characterization of indolinones which preferentially inhibit VEGF-C- and VEGF-D-induced activation of VEGFR-3 rather than VEGFR-2. Eur J Biochem. 2001 Nov;268(21):5530-40.
690 Kirkin V, et al. MAZ51, an indolinone that inhibits endothelial cell and tumor cell growth in vitro, suppresses tumor growth in vivo. Int J Cancer. 2004 Dec 20;112(6):986-93.
691 Hiroyasu Koga, et al. Short-term therapy with luliconazole, a novel topical antifungal imidazole, in guinea pig models of tinea corporis and tinea pedis. Antimicrob Agents Chemother. 2012 Jun;56(6):3138-43.
692 Hiroyasu Koga, et al. In vitro antifungal activities of luliconazole, a new topical imidazole. Med Mycol. 2009;47(6):640-7.
693 LUZU (luliconazole) Cream, 1% for topical use
694 J Biol Chem 235:PC13 (1960); J Heart Lung Transplant 13:481 (1994); Cosmet Dermatol 21:76 (2008)|
695 Cardoso T, et al. Lactobionic Acid as a Potential Food Ingredient: Recent Studies and Applications. J Food Sci. 2019 Jul;84(7):1672-1681.
696 Vet Rec 79:590 (1966); J Parasitol 53:1085 (9167); J Pharm Pharmacol 22:26 (1970)
697 Yu L. Inhibitory effects of (S)- and (R)-6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acids on tyrosinase activity. J Agric Food Chem. 2003 Apr 9;51(8):2344-7.
698 Cheng Y, et al. Current Development Status of MEK Inhibitors. Molecules. 2017 Sep 26;22(10). pii: E1551.
699 Selcher JC, et al. A necessity for MAP kinase activation in mammalian spatial learning. Learn Mem. 1999 Sep-Oct;6(5):478-90.
700 Yusaku Hori, et al. E7386, an orally active CBP/beta-catenin modulator, induces T cells infiltration into tumor and enhances antitumor activity of anti-PD-1 mAb in Wnt1 tumor syngeneic mice model. Cancer Res 2017;77(13 Suppl):Abstract nr 5172.
701 J Antimicrob Chemother 14:441 (1984); Antimicrob Agents Chemother 29:52 (1986); J Hosp Infect 7 Suppl A:47 (1986)
702 J Am Med Assoc 132:126 (1946); IARC Monographs 50:143 (1990)
703 Humphries-Bickley T, et al. Characterization of a Dual Rac/Cdc42 Inhibitor MBQ-167 in Metastatic Cancer. Mol Cancer Ther. 2017 May;16(5):805-818.
704 Parry D, et al.&#x0D; Dinaciclib (SCH 727965), a novel and potent cyclin-dependent kinase inhibitor.&#x0D; Mol Cancer Ther. 2010 Aug;9(8):2344-53.
705 Feldmann G, et al. Cyclin-dependent kinase inhibitor Dinaciclib (SCH727965) inhibits pancreatic cancer growth and progression in murine xenograft models. Cancer Biol Ther. 2011 Oct 1;12(7):598-609.
706 Zhang Y, et al. Novel ADAM-17 inhibitor ZLDI-8 enhances the in vitro and in vivo chemotherapeutic effects of Sorafenib on hepatocellular carcinoma cells. Cell Death Dis. 2018 Jul 3;9(7):743.
707 Hou X, et al. Fast identification of novel lymphoid tyrosine phosphatase inhibitors using target-ligand interaction-based virtual screening. J Med Chem. 2014 Nov 26;57(22):9309-22.
708 Can Med Assoc J 78:206 (1958)
709 Kaiser M, et al. Antitrypanosomal activity of fexinidazole, a new oral nitroimidazole drug candidate for treatment of sleeping sickness. Antimicrob Agents Chemother. 2011 Dec;55(12):5602-8.
710 Lin K, et al. VX-950, a novel hepatitis C virus (HCV) NS3-4A protease inhibitor, exhibits potent antiviral activities in HCv replicon cells. Antimicrob Agents Chemother. 2006 May;50(5):1813-22.
711 Perni RB, et al. Preclinical profile of VX-950, a potent, selective, and orally bioavailable inhibitor of hepatitis C virus NS3-4A serine protease. Antimicrob Agents Chemother. 2006 Mar;50(3):899-909.
712 Zhang X, et al. Discovery and evolution of aloperine derivatives as a new family of HCV inhibitors with novel mechanism. Eur J Med Chem. 2018 Jan 1;143:1053-1065.
713 Wan H, et al. Discovery of a Highly Selective JAK2 Inhibitor, BMS-911543, for the Treatment of Myeloproliferative Neoplasms. ACS Med Chem Lett. 2015 Jul 12;6(8):850-5.
714 Mace TA, et al. Single agent BMS-911543 Jak2 inhibitor has distinct inhibitory effects on STAT5 signaling in genetically engineered mice with pancreatic cancer. Oncotarget. 2015 Dec 29;6(42):44509-22.
715 Makovski V, et al. Farnesylthiosalicylic acid (salirasib) inhibits Rheb in TSC2-null ELT3 cells: a potential treatment for lymphangioleiomyomatosis.&#x0D; Int J Cancer. 2012 Mar 15;130(6):1420-9.
716 Nevo Y, et al. Chapman J. The Ras antagonist, farnesylthiosalicylic acid (FTS), decreases fibrosis and improves muscle strength in dy/dy mouse model of muscular dystrophy.&#x0D; PLoS One. 2011 Mar 22;6(3):e18049.
717 Charette N, et al. Salirasib inhibits the growth of hepatocarcinoma cell lines in vitro and tumor growth in vivo through ras and mTOR inhibition.&#x0D; Mol Cancer. 2010 Sep 22;9:256.
718 Liu K, et al. Biological characterization of 3-(2-amino-ethyl)-5-[3-(4-butoxyl-phenyl)-propylidene]-thiazolidine-2,4-dione (K145) as a selective sphingosine kinase-2 inhibitor and anticancer agent. PLoS One. 2013;8(2):e56471.
719 J. Med. Chem. (1991), 34(7), 2231-41; J. Infect. Dis. (1991), 163(5), 966-70; Science (1990), 250(4986), 1411-13
720 Godinho SA, et al. Causes and consequences of centrosome abnormalities in cancer. Philos Trans R Soc Lond B Biol Sci. 2014 Sep 5;369(1650).
721 Discovery and mechanistic study of a small molecule inhibitor for motor protein KIFC1. Wu J, et al. ACS Chem Biol. 2013 Oct 18;8(10):2201-8.
722 Siemon G, et, al. [The effect of fominoben and oxyethyltheophylline in combination on pulmonary function and pulmonary hemodynamics in chronic-obstructive diseases of the airways (author's transl)]. Arzneimittelforschung. 1978;28(4):698-700.
723 Ufkes JG, et, al. Efficacy of theophylline and its N-7-substituted derivatives in experimentally induced bronchial asthma in the guinea-pig. Arch Int Pharmacodyn Ther. 1981 Oct;253(2):301-14.
724 Life Sci 17: 1777 (1975)
725 Wedge SR, et al. ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. Cancer Res. 2002 Aug 15;62(16):4645-55.
726 Hegedus C, et al. Interaction of the EGFR inhibitors gefitinib, vandetanib, pelitinib and neratinib with the ABCG2 multidrug transporter: implications for the emergence and reversal of cancer drug resistance. Biochem Pharmacol. 2012 Aug 1;84(3):260-7.
727 Takeda H, et al. Vandetanib is effective in EGFR-mutant lung cancer cells with PTEN deficiency. Exp Cell Res. 2013 Feb 15;319(4):417-23.
728 Inoue K, et al. Vandetanib, an inhibitor of VEGF receptor-2 and EGF receptor, suppresses tumor development and improves prognosis of liver cancer in mice. Clin Cancer Res. 2012 Jul 15;18(14):3924-33.
729 Rai R, et al. A novel acetyltransferase p300 inhibitor ameliorates hypertension-associated cardio-renal fibrosis. Epigenetics. 2017;12(11):1004-1013.
730 Sun XJ, et al. The Role of Histone Acetyltransferases in Normal and Malignant Hematopoiesis. Front Oncol. 2015 May 26;5:108.
731 Rai R, et al. Acetyltransferase p300 inhibitor reverses hypertension-induced cardiac fibrosis.J Cell Mol Med. 2019 Apr;23(4):3026-3031.
732 https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=TACROLIMUS&cntry=&state=&city=&dist=&Search=Search
733 ZHU, D., et al., In vitro activities of cefoselis compared to β-lactams and other antibacterial agents aganst gram-positive and gram-negative clinical isolates. Chinese Journal of Infection and Chemotherapy, 2011. 4: p. 002.
734 King, A., L. Bethune, and I. Phillips, The Comparative In Vitro Activity of FK-037 (Cefoselis), a New Broad-Spectrum Cephalosporin. Clin Microbiol Infect, 1995. 1(1): p. 13-17.
735 K Ohtaki, et al. Cefoselis, a beta-lactam antibiotic, easily penetrates the blood-brain barrier and causes seizure independently by glutamate release. J Neural Transm (Vienna). 2004 Dec;111(12):1523-35.
736 Ann. Pharm. Fr(1970), 28(7-8), 497-509. ; Therapie (1967), 22(1), 137-47. ; Therapie (1965), 20(5), 1305-10.
737 Lock R1, et al. Initial testing (stage 1) of the BH3 mimetic ABT-263 by the pediatric preclinical testing program. Pediatr Blood Cancer. 2008 Jun;50(6):1181-1189.
738 Wong M, et al. Navitoclax (ABT-263) reduces Bcl-x(L)-mediated chemoresistance in ovarian cancer models.Mol Cancer Ther. 2012 Apr;11(4):1026-1035.
739 Chen J, et al. The Bcl-2/Bcl-X(L)/Bcl-w inhibitor, navitoclax, enhances the activity of chemotherapeutic agents in vitro and in vivo. Mol Cancer Ther. 2011 Dec;10(12):2340-9.
740 Bhumika D Patel, et al. Recent approaches to medicinal chemistry and therapeutic potential of dipeptidyl peptidase-4 (DPP-4) inhibitors. Eur J Med Chem. 2014 Mar 3;74:574-605.
741 Charles E Grimshaw, et al. Trelagliptin (SYR-472, Zafatek), Novel Once-Weekly Treatment for Type 2 Diabetes, Inhibits Dipeptidyl Peptidase-4 (DPP-4) via a Non-Covalent Mechanism. PLoS One. 2016 Jun 21;11(6):e0157509.
742 Shiliang Li, et al. Discovery of a Natural-Product-Derived Preclinical Candidate for Once-Weekly Treatment of Type 2 Diabetes. J Med Chem. 2019 Mar 14;62(5):2348-2361.
743 Matsuzawa Y, et al. Activation of cytosolic phospholipase A2alpha by epidermal growth factor (EGF) and phorbol ester in HeLa cells: different effects of inhibitors for EGF receptor, protein kinase C, Src, and C-Raf. J Pharmacol Sci. 2009 Oct;111(2):182-92
744 Invest Urol 12:381 (1975); 18:102 (1980)
745 Florian MC et al. Cdc42 activity regulates hematopoietic stem cell aging and rejuvenation. Cell Stem Cell, 2012 May 4, 10(5):520-30.
746 Peterson JR et al. Biochemical suppression of small-molecule inhibitors: a strategy to identify inhibitor targets and signaling pathway components.
747 Marschall M, et al. In vitro evaluation of the activities of the novel anticytomegalovirus compound AIC246 (letermovir) against herpesviruses and other human pathogenic viruses. Antimicrob Agents Chemother. 2012 Feb;56(2):1135-7.
748 Goldner T, et al. The novel anticytomegalovirus compound AIC246 (Letermovir) inhibits human cytomegalovirus replication through a specific antiviral mechanism that involves the viral terminase. J Virol. 2011 Oct;85(20):10884-93.
749 Lischka P, et al. In vitro and in vivo activities of the novel anticytomegalovirus compound AIC246. Antimicrob Agents Chemother. 2010 Mar;54(3):1290-7.
750 Wildum S, et al. In vitro drug combination studies of Letermovir (AIC246, MK-8228) with approved anti-human cytomegalovirus (HCMV) and anti-HIV compounds in inhibition of HCMV and HIV replication. Antimicrob Agents Chemother. 2015;59(6):3140-8.
751 Wei Xu, et al. Safety, Tolerability and Efficacy of Orelabrutinib, Once a Day, to Treat Chinese Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Cell Leukemia. Blood (2019) 134 (Supplement_1): 4319.
752 BTK Inhibitor ICP-022.
753 Pulm. Pharmacol. Ther. (1997), 10(2), 97-104; J. Pharmacol. Exp. Ther. (1974), 189(1), 616-25; J. Med. Chem. (1971), 14(9), 895-6
754 https://clinicaltrials.gov/ct2/show/NCT04610502?term=Chlorpheniramine&cond=Covid19&draw=2&rank=1
755 Jon I Williams, et al. Non-clinical pharmacology, pharmacokinetics, and safety findings for the antihistamine bepotastine besilate. Curr Med Res Opin. 2010 Oct;26(10):2329-38.
756 Tsugunobu Andoh, et al. Suppression by bepotastine besilate of substance P-induced itch-associated responses through the inhibition of the leukotriene B4 action in mice. Eur J Pharmacol. 2006 Oct 10;547(1-3):59-64.
757 Arzneim Forsch 15:1441 (1965); Anal Profiles Drug Subs 2:487 (1973)
758 Kalbhen DA, et al. Nutmeg as a narcotic. A contribution to the chemistry and pharmacology of nutmeg (Myristica fragrans).Angew Chem Int Ed Engl. 1971 Jun;10(6):370-4.
759 Dawidowicz AL, et al. Simple and rapid determination of myristicin in human serum.Forensic Toxicol. 2013 Jan;31(1):119-123. Epub 2012 Aug 15.
760 Yang X, et al. Nsc23925 prevents the development of paclitaxel resistance by inhibiting the introduction of P-glycoprotein and enhancing apoptosis. Int J Cancer. 2015 Oct 15;137(8):2029-39.
761 Duan Z, et al. NSC23925, identified in a high-throughput cell-based screen, reverses multidrug resistance. PLoS One. 2009 Oct 12;4(10):e7415.
762 Wu Q, et al. Characterization of the biosynthesis gene cluster for the pyrrole polyether antibiotic calcimycin(A23187) in Streptomyces chartreusis NRRL 3882. Antimicrob Agents Chemother. 2011 Mar;55(3):974-82.
763 Elliott JI, et al. IKCa1 activity is required for cell shrinkage, phosphatidylserine translocation and death in Tlymphocyte apoptosis. EMBO Rep. 2003 Feb;4(2):189-94.
764 Engedal N, et al. Modulation of intracellular calcium homeostasis blocks autophagosome formation. Autophagy. 2013 Oct;9(10):1475-90.
765 Mawatwal S, et al. Calcimycin mediates mycobacterial killing by inducing intracellular calcium-regulated autophagy in a P2RX7 dependent manner. Biochim Biophys Acta Gen Subj. 2017 Dec;1861(12):3190-3200.
766 Wang JP, et al. Effect of norathyriol, isolated from Tripterospermum lanceolatum, on A23187-induced pleurisy and analgesia in mice. Naunyn Schmiedebergs Arch Pharmacol. 1994 Jul;350(1):90-5.
767 Katayama R, et al. The new-generation selective ROS1/NTRK inhibitor DS-6051b overcomes crizotinib resistant ROS1-G2032R mutation in preclinical models. Nat Commun. 2019;10(1):3604. Published 2019 Aug 9.
768 Fujiwara Y, et al. Safety and pharmacokinetics of DS-6051b in Japanese patients with non-small cell lung cancer harboring ROS1 fusions: a phase I study. Oncotarget. 2018;9(34):23729-23737. Published 2018 May 4.
769 Flamme I, et al. Mimicking hypoxia to treat anemia: HIF-stabilizer BAY 85-3934 (Molidustat) stimulates erythropoietin production without hypertensive effects. PLoS One. 2014 Nov 13;9(11):e111838.
770 J Neurosci 22:8942 (2002); Nature Med 8:143 (2002); J Biol Chem 278:3825 (2003); Clin Invest 116:1410 (2006)
771 Chen Z, et al. Novel 1,3,4-Selenadiazole Containing Kidney-Type Glutaminase Inhibitors Showed Improved Cellular Uptake and Antitumor Activity. J Med Chem. 2018 Dec 13.
772 J Pharm Exp Ther 89:205 (1947); 99:171 (1950) ; Arzneim Forsch 20:1024 (1970)
773 Rho JK, et al. MET and AXL inhibitor NPS-1034 exerts efficacy against lung cancer cells resistant to EGFR kinase inhibitors because of MET or AXL activation. Cancer Res. 2014 Jan 1;74(1):253-62.
774 Shin JS, et al. NPS-1034, a novel MET inhibitor, inhibits the activated MET receptor and its constitutively active mutants. Invest New Drugs. 2014 Jun;32(3):389-99.
775 https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=L-Ascorbic+acid&cntry=&state=&city=&dist=
776 Chem Pharm Bull 34: 2506 (1986); 35: 3597 (1987)
777 Kaileh M, et al. Withaferin a strongly elicits IkappaB kinase beta hyperphosphorylation concomitant with potent inhibition of its kinase activity. J Biol Chem. 2007 Feb 16;282(7):4253-64. Epub 2006 Dec 6.
778 Bargagna-Mohan P, et al. The tumor inhibitor and antiangiogenic agent withaferin A targets the intermediate filament protein vimentin. Chem Biol. 2007 Jun;14(6):623-34.
779 Kakar SS, et al. Withaferin A (WFA) inhibits tumor growth and metastasis by targeting ovarian cancer stem cells. Oncotarget. 2017 Aug 10;8(43):74494-74505.
780 Moorthy BT, et al. Novel rhodanine derivatives induce growth inhibition followed by apoptosis. Bioorg Med Chem Lett. 2010 Nov 1;20(21):6297-301.
781 Ajaybabu V Pobbati, et al. A combat with the YAP/TAZ-TEAD oncoproteins for cancer therapy. Theranostics. 2020 Feb 18;10(8):3622-3635.
782 Xuan Zhang, et al. Targeting of mutant p53-induced FoxM1 with Thiostrepton induces cytotoxicity and enhances carboplatin sensitivity in cancer cells. Oncotarget. 2014 Nov 30;5(22):11365-80.
783 Aniruddha Sengupta, et al. The dual inhibitory effect of Thiostrepton on FoxM1 and EWS/FLI1 provides a novel therapeutic option for Ewing's sarcoma. Int J Oncol. 2013 Sep;43(3):803-12. |Nature 225:233 (1970); J Antibiot 36:799, 814, 831(1983); 42:1649 (1989)
784 Zhou Y, et al. Spiroindolone that inhibits PfATPase4 is a potent, cidal inhibitor of Toxoplasma gondii tachyzoites in vitro and in vivo. Antimicrob Agents Chemother. 2014;58(3):1789-92.
785 van Pelt-Koops JC, et al. The spiroindolone drug candidate NITD609 potently inhibits gametocytogenesis and blocks Plasmodium falciparum transmission to anopheles mosquito vector. Antimicrob Agents Chemother. 2012 Jul;56(7):3544-8.
786 Rottmann M, et al. Spiroindolones, a potent compound class for the treatment of malaria. Science. 2010 Sep 3;329(5996):1175-80.
787 Sun Q, et al. Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy. Cancer Biol Ther. 2014;15(12):1635-45.
788 Lotilaner, et al. The novel isoxazoline ectoparasiticide lotilaner (Credelio™): a non-competitive antagonist specific to invertebrates γ-aminobutyric acid-gated chloride channels (GABACls). Parasit Vectors. 2017 Nov 1;10(1):530.
789 Rajamani S et al. The novel late Na+ current inhibitor, GS-6615 (eleclazine) and its anti-arrhythmic effects in rabbit isolated heart preparations. Br J Pharmacol. 2016 Jul 23.
790 Justo F et al. Inhibition of the cardiac late sodium current with eleclazine protects against ischemia-induced vulnerability to atrial fibrillation and reduces atrial and ventricular repolarization abnormalities in the absence and presence of concurrent adrenergic stimulation. Heart Rhythm. 2016 Sep;13(9):1860-7.
791 Cazzola M. Aclidinium bromide, a novel long-acting muscarinic M3 antagonist for the treatment of COPD. Curr Opin Investig Drugs. 2009 May;10(5):482-90.
792 Joos GF. Potential for long-acting muscarinic antagonists in chronic obstructive pulmonary disease. Expert Opin Investig Drugs. 2010 Feb;19(2):257-64.
793 Sentellas S, Ramos I, Albertí J et al. Aclidinium bromide, a new, long-acting, inhaled muscarinic antagonist: in vitro plasma inactivation and pharmacological activity of its main metabolites. Eur J Pharm Sci. 2010 Mar 18;39(5):283-90.
794 Sims MW, Panettieri RA Jr. Profile of aclidinium bromide in the treatment of chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2011;6:457-66.
795 Ma R, et al. AZ304, a novel dual BRAF inhibitor, exerts anti-tumour effects in colorectal cancer independently of BRAF genetic status. Br J Cancer. 2018 May;118(11):1453-1463.
796 Kim YS, et al. Synthesis of 2',3',4'-trihydroxyflavone (2-D08), an inhibitor of protein sumoylation. Bioorg Med Chem Lett. 2014 Feb 15;24(4):1094-7.
797 Fujino N, et al. Phenotypic screening identifies Axl kinase as a negative regulator of an alveolar epithelial cell phenotype. Lab Invest. 2017 Sep;97(9):1047-1062.
798 Ghosh H, et al. Several posttranslational modifications act in concert to regulate gephyrin scaffolding and GABAergic transmission. Nat Commun. 2016 Nov 7;7:13365. doi: 10.1038/ncomms13365.
799 Kettle JG, et al. Discovery of N-(4-{[5-Fluoro-7-(2-methoxyethoxy) quinazolin-4-yl]amino} phenyl)-2-[4-(propan-2-yl)-1 H-1,2,3-triazol-1-yl]acetamide (AZD3229), a Potent Pan-KIT Mutant Inhibitor for the Treatment of Gastrointestinal Stromal Tumors. J Med Chem. 2018 Oct 11;61(19):8797-8810.
800 Brit J Pharmacol 109: 200 (1993); Gen Pharmacol 31:503 (1998)
801 Norman P, et al. Investigational p38 inhibitors for the treatment of chronic obstructive pulmonary disease. Expert Opin Investig Drugs. 2015 Mar;24(3):383-92.
802 De Buck S, et al. Population PK-PD Model for Tolerance Evaluation to the p38 MAP Kinase Inhibitor BCT197. CPT Pharmacometrics Syst Pharmacol. 2015 Dec;4(12):691-700.
803 Large CH, et al. The efficacy of sodium channel blockers to prevent phencyclidine-induced cognitive dysfunction in the rat: potential for novel treatments for schizophrenia. J Pharmacol Exp Ther. 2011 Jul;338(1):100-13.
804 Lingling Zhang, et al. Inhibition of wild-type p53-induced phosphatase 1 promotes liver regeneration in mice by direct activation of mammalian target of rapamycin. Hepatology. 2015 Jun;61(6):2030-41.
805 S Rayter, et al. A chemical inhibitor of PPM1D that selectively kills cells overexpressing PPM1D. Oncogene. 2008 Feb 14;27(8):1036-44.
806 Ren JX, et al. Identification of novel dual-specificity phosphatase 26 inhibitors by a hybrid virtual screening approach based on pharmacophore and molecular docking. Biomed Pharmacother. 2017 May;89:376-385.
807 Murakami Y, et al. Dehydrodiisoeugenol, an isoeugenol dimer, inhibits lipopolysaccharide-stimulated nuclear factor kappa B activation and cyclooxygenase-2 expression in macrophages. Arch Biochem Biophys. 2005 Feb 15;434(2):326-32.
808 Lv QQ, et al. Metabolic profiling of dehydrodiisoeugenol using xenobiotic metabolomics. J Pharm Biomed Anal. 2017 Oct 25;145:725-733.
809 T I Ng , et al. Selection and Characterization of Varicella-Zoster Virus Variants Resistant to (R)-9-[4-hydroxy-2-(hydroxymethy)butyl]guanine. Antimicrob Agents Chemother. 2001 Jun;45(6):1629-36.
810 Currier MA, et al. Identification of Cancer-Targeted Tropomyosin Inhibitors and Their Synergy with Microtubule Drugs.Mol Cancer Ther. 2017 Aug;16(8):1555-1565.
811 Reina JC, et al. A Quorum-Sensing Inhibitor Strain of Vibrio alginolyticus Blocks Qs-Controlled Phenotypes in Chromobacterium violaceum and Pseudomonas aeruginosa. Mar Drugs. 2019;17(9):494. Published 2019 Aug 24.
812 Kunimoto S, et al. Reversal of resistance by N-acetyltyramine or N-acetyl-2-phenylethylamine in doxorubicin-resistant leukemia P388 cells. J Antibiot (Tokyo). 1987;40(11):1651-1652.
813 Hai-Tao Xiao, et al. Acetylcholinesterase inhibitors from Corydalis yanhusuo. Nat Prod Res. 2011 Sep;25(15):1418-22.
814 Hui-Qiang Wang, et al. Corydaline inhibits enterovirus 71 replication by regulating COX-2 expression. J Asian Nat Prod Res. 2017 Nov;19(11):1124-1133.
815 Teresa Kaserer, et al. Identification and characterization of plant-derived alkaloids, corydine and corydaline, as novel mu opioid receptor agonists. Sci Rep. 2020 Aug 14;10(1):13804.
816 Hypertension 30:912 (1997); J Thorac Cardiovasc Surg 124:352 (2002)
817 Bougoudogo, F, Fournier, J. M.; Dodin, A. "In vitro sensitivity of Vibrio cholerae serotype 0:139 to an intestinal antiseptic tiliquinol-tilbroquinol combination". Bulletin de la Societe de pathologie exotique (1990) 87 (1): 38-40.
818 International Drug Names
819 Okura N, et al. ONO-7475, a Novel AXL Inhibitor, Suppresses the Adaptive Resistance to Initial EGFR-TKI Treatment in EGFR-Mutated Non-Small Lung Cancer.Clin Cancer Res. 2020 Jan 17.
820 Ruvolo PP, et al. Anexelekto/MER tyrosine kinase inhibitor ONO-7475 arrests growth and kills FMS-like tyrosine kinase 3-internal tandem duplication mutant acute myeloid leukemia cells by diverse mechanisms.Haematologica. 2017 Dec;102(12):2048-2057.
821 James RG, et al. WIKI4, a novel inhibitor of tankyrase and Wnt/ß-catenin signaling. PLoS One. 2012;7(12):e50457.
822 Haikarainen T, et al. Structural basis and selectivity of tankyrase inhibition by a Wnt signaling inhibitor WIKI4. PLoS One. 2013 Jun 6;8(6):e65404.
823 Sadava D, et al. The effect of brassinolide, a plant steroid hormone, on drug resistant small-cell lung carcinoma cells. Biochem Biophys Res Commun. 2017 Nov 4;493(1):783-787.
824 Yusheng Hu, et al. Coixol Suppresses NF-κB, MAPK Pathways and NLRP3 Inflammasome Activation in Lipopolysaccharide-Induced RAW 264.7 Cells. Molecules
825 https://clinicaltrials.gov/ct2/show/NCT04751669?term=Tocopherol&cond=Covid19&draw=2&rank=2
826 Jayathilaka K, et al. A chemical compound that stimulates the human homologous recombination protein RAD51. Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15848-53.
827 Song J, et al. RS-1 enhances CRISPR/Cas9- and TALEN-mediated knock-in efficiency. Nat Commun. 2016 Jan 28;7:10548.
828 Smith MA,et al. Profile of paritaprevir/ritonavir/ombitasvir plus dasabuvir in the treatment of chronic hepatitis C virus genotype 1 infection. Drug Des Devel Ther. 2015 Nov 13;9:6083-94.
829 Schnell G, et al. Hepatitis C Virus Genotype 4 Resistance and Subtype Demographic Characterization of Patients Treated with Ombitasvir plus Paritaprevir/ritonavir. Antimicrob Agents Chemother. 2015 Aug 17. pii: AAC.01229-15.
830 Expert Opin. Invest. Drugs (2007), 16(10), 1615-1625; Drugs (1992), 43(6), 873-88; Epilepsia (1987), 28(6), 693-8
831 Wang JB, et al. l-tetrahydropalamatine: a potential new medication for the treatment of cocaine addiction. Future Med Chem. 2012 Feb;4(2):177-86.
832 Liu YL, et al. Effects of l-tetrahydropalmatine on locomotor sensitization to oxycodone in mice. Acta Pharmacol Sin. 2005 May;26(5):533-8.
833 Rao V, et al. Effective 'Activated PI3Kd Syndrome' -targeted therapy with PI3Kd inhibitor leniolisib. The New England journal of medicine: NEJM. ISSN 0028-4793; 1533-4406
834 Alpert JS, et al. Chemistry, pharmacology, antiarrhythmic efficacy and adverse effects of tocainide hydrochloride, an orally active structural analog of lidocaine. Pharmacotherapy. 1983 Nov-Dec;3(6):316-23.
835 De Luca A,et al.Optimal requirements for high affinity and use-dependent block of skeletal muscle sodium channel by N-benzyl analogs of tocainide-like compounds.Mol Pharmacol. 2003 Oct;64(4):932-45.
836 Gessier F, et al. Identification and characterization of small molecule modulators of the Epstein-Barr virus-induced gene 2 (EBI2) receptor. J Med Chem. 2014 Apr 24;57(8):3358-68.
837 Lee S, et al. Relative protective activities of quercetin, quercetin-3-glucoside, and rutin in alcohol-induced liver injury. J Food Biochem. 2019 Aug 5:e13002.
838 Tan C, et al. Modulation of nuclear factor-κB signaling and reduction of neural tube defects by quercetin-3-glucoside in embryos of diabetic mice. Am J Obstet Gynecol. 2018 Aug;219(2):197.e1-197.e8.
839 Sabine Bachmaier, et al. Nucleoside analogue activators of cyclic AMP-independent protein kinase A of Trypanosoma. Nat Commun. 2019 Mar 29;10(1):1421.
840 Int J Pharm 300:38 (2005)
841 Stemp G, et al. Design and synthesis of trans-N-[4-[2-(6-cyano-1,2,3, 4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-4-quinolinecarboxamide (SB-277011): A potent and selective dopamine D(3) receptor antagonist with high oral bioavailability and CNS penetration in the rat. J Med Chem. 2000 May 4;43(9):1878-85.
842 Rui Song, et al. YQA14: A Novel Dopamine D3 Receptor Antagonist That Inhibits Cocaine Self-Administration in Rats and Mice, but Not in D3 Receptor-Knockout Mice. Addict Biol
843 Phytochemistry 17:1383 (1978)
844 Erpenbeck, V. J. et al. Pharmacokinetics, Safety, and Tolerability of Fevipiprant (QAW039), a Novel CRTh2 Receptor Antagonist: Results From 2 Randomized, Phase 1, Placebo-Controlled Studies in Healthy Volunteers. Clinical pharmacology in drug development 5, 306-313, doi:10.1002/cpdd.244 (2016).
845 Sykes, D. A. et al.Fevipiprant (QAW039), a Slowly Dissociating CRTh2 Antagonist with the Potential for Improved Clinical Efficacy. Molecular pharmacology 89, 593-605, doi:10.1124/mol.115.101832 (2016).
846 Kim, S.J., et al., Geniposidic acid protects against D-galactosamine and lipopolysaccharide-induced hepatic failure in mice. J Ethnopharmacol, 2013. 146(1): p. 271-7.
847 Hsu, H.Y., et al., Comparisons of geniposidic acid and geniposide on antitumor and radioprotection after sublethal irradiation. Cancer Lett, 1997. 113(1-2): p. 31-7.
848 Harris PA et al. DNA-Encoded Library Screening Identifies Benzo[b][1,4]oxazepin-4-ones as Highly Potent and Monoselective Receptor Interacting Protein 1 Kinase Inhibitors. J Med Chem, 2016 Mar 10, 59(5):2163-78.
849 Lee HL, et al. Simultaneous flow cytometric immunophenotyping of necroptosis, apoptosis and RIP1-dependent apoptosis. Methods. 2018 Feb 1;134-135:56-66.
850 Sykes DB et al. Discovering Small Molecules that Overcome Differentiation Arrest in Acute Myeloid Leukemia. National Center for Biotechnology Information (US); 2010-2013 Dec 15.
851 David B Sykes, et al. Inhibition of Dihydroorotate Dehydrogenase Overcomes Differentiation Blockade in Acute Myeloid Leukemia. Cell. 2016 Sep 22;167(1):171-186.e15.
852 Timothy A Lewis, et al. Development of ML390: A Human DHODH Inhibitor That Induces Differentiation in Acute Myeloid Leukemia. ACS Med Chem Lett. 2016 Sep 28;7(12):1112-1117.
853 Kyle R. Simonetta, et al. Prospective discovery of small molecule enhancers of an E3 ligase-substrate interaction. Nature Communications. 2019 March.
854 Bath CP, et al. The effects of ifenprodil and eliprodil on voltage-dependent Ca2+ channels and in gerbil global cerebral ischaemia. Eur J Pharmacol. 1996 Mar 28;299(1-3):103-12.
855 Lengyel C, et al. Effect of a neuroprotective drug, eliprodil on cardiac repolarisation: importance of the decreased repolarisation reserve in the development of proarrhythmic risk. Br J Pharmacol. 2004 Sep;143(1):152-8.
856 Olaharski AJ, et al. The flavoring agent Dihydrocoumarin reverses epigenetic silencing and inhibits sirtuindeacetylases. PLoS Genet. 2005 Dec;1(6):e77.
857 Modulation of Sirt1/NF-κB interaction of evogliptin is attributed to inhibition of vascular inflammatory response leading to attenuation of atherosclerotic plaque formation. Biochem Pharmacol. 2019 Oct;168:452-464.
858 Robke L, et al. Phenotypic Identification of a Novel Autophagy Inhibitor Chemotype Targeting Lipid Kinase VPS34. Angew Chem Int Ed Engl. 2017 Jul 3;56(28):8153-8157.
859 Dayal N, et al. Potently inhibiting cancer cell migration with novel 3H-pyrazolo[4,3-f]quinoline boronic acid ROCK inhibitors. Eur J Med Chem. 2019 Oct 15;180:449-456.
860 Yano W, et al. TAS-114, a First-in-Class Dual dUTPase/DPD Inhibitor, Demonstrates Potential to Improve Therapeutic Efficacy of Fluoropyrimidine-Based Chemotherapy. Mol Cancer Ther. 2018 Aug;17(8):1683-1693.
861 Guo B, et al. Clinical Pharmacokinetics of Levornidazole in Elderly Subjects and Dosing Regimen Evaluation Using Pharmacokinetic/Pharmacodynamic Analysis. Clin Ther. 2017 Jul;39(7):1336-1346.
862 Biochem. Pharmacol. (1964), 13(2), 153-8; Arch. Int. Pharmacodyn. Ther. (1960), 126, 386-92. ; Therapie (1954), 9, 64-7.
863 Chou CJ, et al. Pimelic diphenylamide 106 is a slow, tight-binding inhibitor of class I histone deacetylases. J Biol Chem. 2008 Dec 19;283(51):35402-35409.
864 Xu C, et al. Chemical probes identify a role for histone deacetylase 3 in Friedreich's ataxia gene silencing. Chem Biol. 2009 Sep 25;16(9):980-989.
865 Lee J, et al. Identification of CKD-516: a potent tubulin polymerization inhibitor with marked antitumor activity against murine and human solid tumors. J Med Chem. 2010 Sep 9;53(17):6337-54.
866 Joo I, et al. Intravoxel incoherent motion diffusion-weighted MR imaging for monitoring the therapeutic efficacy of the vascular disrupting agent CKD-516 in rabbit VX2 liver tumors. Radiology. 2014 Aug;272(2):417-26.
867 Luo M, et al. Diethylaminobenzaldehyde is a covalent, irreversible inactivator of ALDH7A1. ACS Chem Biol. 2015 Mar 20;10(3):693-7.
868 Araki N, et al. Screening for androgen receptor activities in 253 industrial chemicals by in vitro reporter gene assays using AR-EcoScreen cells. Toxicol In Vitro. 2005 Sep;19(6):831-42.
869 X. Bao, et al. Combination of a Novel EP4 Antagonist E7046 and Radiation Therapy Promotes Anti-tumor Immune Response and Tumor Rejection in Preclinical Tumor Models. International Journal of Radiation Oncology Biology Physics
870 Diana I. Albu, et al. EP4 Antagonism by E7046 diminishes Myeloid immunosuppression and synergizes with Treg-reducing IL-2-Diphtheria toxin fusion protein in restoring anti-tumor immunity. OncoImmunology.
871 https://clinicaltrials.gov/ct2/show/NCT04937543?term=GLYCOPYRROLATE&cond=covid&draw=2&rank=1
872 Alvarez C, et al. Brefeldin A (BFA) disrupts the organization of the microtubule and the actin cytoskeletons. Eur J Cell Biol. 1999 Jan;78(1):1-14.
873 Colanzi A, et al. Molecular mechanism and functional role of brefeldin A-mediated ADP-ribosylation of CtBP1/BARS. Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):9794-9.
874 Tseng CN, et al. Brefeldin A reduces anchorage-independent survival, cancer stem cell potential and migration of MDA-MB-231 human breast cancer cells. Molecules. 2014 Oct 29;19(11):17464-77.
875 Wang J, et al. Erythroleukemia cells acquire an alternative mitophagy capability. Sci Rep. 2016 Apr 19;6:24641.
876 Yu C, et al. Small molecules enhance CRISPR genome editing in pluripotent stem cells. Cell Stem Cell. 2015 Feb 5;16(2):142-7.
877 Nozawa N, et al. Subcellular localization of herpes simplex virus type 1 UL51 protein and role of palmitoylation in Golgi apparatus targeting. J Virol. 2003 Mar;77(5):3204-16.
878 Jensen HL, Rygaard J, Norrild B. A time-related study of Brefeldin A effects in HSV-1 infected cultured human fibroblasts. APMIS. 1995;103(7-8):530-539. doi:10.1111/j.1699-0463.1995.tb01402.x
879 https://clinicaltrials.gov/ct2/show/NCT04467931?term=TORSEMIDE&cond=COVID-19&draw=2&rank=1
880 Wang Y, et al. A Small Molecule Inhibitor Targeting TRIP13 suppresses multiple myeloma progression. Cancer Res. 2019 Nov 15. pii: canres.3987.2018.
881 Rohn TT, et al. Caspase activation in transgenic mice with Alzheimer-like pathology: results from a pilot study utilizing the caspase inhibitor, Q-VD-OPh. Int J Clin Exp Med. 2009 Nov 5;2(4):300-8.
882 Kuzelová K, et al. Dose-dependent effects of the caspase inhibitor Q-VD-OPh on different apoptosis-related processes. J Cell Biochem. 2011 Nov;112(11):3334-42.
883 Caserta TM, et al. Q-VD-OPh, a broad spectrum caspase inhibitor with potent antiapoptotic properties. Apoptosis. 2003 Aug;8(4):345-52.
884 Chen-Deutsch X, et al. Leuk Res. 2012 Jul;36(7):884-8.&#x0D; The pan-caspase inhibitor Q-VD-OPh has anti-leukemia effects and can interact with vitamin D analogs to increase HPK1 signaling in AML cells.
885 Laforge M, et al. The anti-caspase inhibitor Q-VD-OPH prevents AIDS disease progression in SIV-infected rhesus macaques. J Clin Invest. 2018 Apr 2;128(4):1627-1640.
886 Gianní M, et al. AM580, a stable benzoic derivative of retinoic acid, has powerful and selective cyto-differentiating effects on acute promyelocytic leukemia cells. Blood. 1996 Feb 15;87(4):1520-31.
887 Lu Y, et al. Mechanism of inhibition of MMTV-neu and MMTV-wnt1 induced mammary oncogenesis by RARalpha agonist AM580. Oncogene. 2010 Jun 24;29(25):3665-76.
888 Bosch A, et al. Reversal by RARα agonist Am580 of c-Myc-induced imbalance in RARα/RARγ expression during MMTV-Myc tumorigenesis. Breast Cancer Res. 2012 Aug 24;14(4):R121.
889 Bourne N, et al. Civamide (cis-capsaicin) for treatment of primary or recurrent experimental genital herpes. Antimicrob Agents Chemother. 1999 Nov;43(11):2685-8.
890 Antimicrob Agents Chemother 44:1604 (2000); Expert Opin Pharmacother 5:1117 (2004)
891 DEREK N. MIDDLEMISS, et al. 8-HYDROXY-2-(DI-n-PROPYLAMINO)-TETRALIN DISCRIMINATES BETWEEN SUBTYPES OF
892 Bard JA, et al. Cloning of a novel human serotonin receptor (5-HT7) positively linked to adenylate cyclase. J Biol Chem. 1993 Nov 5;268(31):23422-6.
893 Mori T, et al. Narcolepsy-like sleep disturbance in orexin knockout mice are normalized by the 5-HT1A receptor agonist 8-OH-DPAT. Psychopharmacology (Berl). 2016 Jun;233(12):2343-53.
894 Pei Z, et al. Discovery and Biological Profiling of Potent and Selective mTOR Inhibitor GDC-0349. ACS Med Chem Lett. 2012 Nov 29;4(1):103-7.
895 Shino M, et al. In vivo and in vitro evidence for the inhibition of homogentisate solanesyltransferase by cyclopyrimorate. Pest Manag Sci. 2019 Nov 27.
896 Shino M, et al. Action mechanism of bleaching herbicide cyclopyrimorate, a novel homogentisate solanesyltransferase inhibitor. J Pestic Sci. 2018 Nov 20;43(4):233-239.
897 Aronov, Alex M., et al. Structure-Guided Design of Potent and Selective Pyrimidylpyrrole Inhibitors of Extracellular Signal-Regulated Kinase (ERK) Using Conformational Control. Journal of Medicinal Chemistry (2009), 52(20), 6362-6368.
898 Krepler C, et al. Personalized Preclinical Trials in BRAF Inhibitor-Resistant Patient-Derived Xenograft Models Identify Second-Line Combination Therapies. Clin Cancer Res. 2016 Apr 1;22(7):1592-602.
899 Friesen WJ, et al. The nucleoside analog clitocine is a potent and efficacious readthrough agent. RNA. 2017;23(4):567-577.
900 Sun JG, et al. Clitocine potentiates TRAIL-mediated apoptosis in human colon cancer cells by promoting Mcl-1 degradation. Apoptosis. 2016;21(10):1144-1157.
901 Jorg Eberling, et al. Chemoselective Removal of Protecting Groups from O-Glycosyl Amino Acid and Peptide (Methoxyethoxy)ethyl Esters Using Lipases and Papain. J. Org. Chem., 1996, 61 (8), pp 2638–2646
902 Ban HS, et al. The novel hypoxia-inducible factor-1α inhibitor IDF-11774 regulates cancer metabolism, thereby suppressing tumor growth. Cell Death Dis. 2017 Jun 1;8(6):e2843.
903 Mutat. Res. (1975), 32(2), 115-32; Cancer (1972), 30(6), 1639-46; Expert Rev. Anticancer Ther. (2011), 11(3), 403-414
904 Motoko Nakano, et al. Possible involvement of host defense mechanism in the suppression of rat acute reflux esophagitis by the particular histamine H2 receptor antagonist lafutidine. Pharmacology. 2012;90(3-4):205-11.
905 Tetsuhiro Sugiyama, et al. Lafutidine facilitates calcitonin gene-related peptide (CGRP) nerve-mediated vasodilation via vanilloid-1 receptors in rat mesenteric resistance arteries. J Pharmacol Sci. 2008 Mar;106(3):505-11.
906 Mitsuaki Okayama, et al. Protective effect of lafutidine, a novel histamine H2-receptor antagonist, on dextran sulfate sodium-induced colonic inflammation through capsaicin-sensitive afferent neurons in rats. Dig Dis Sci. 2004 Oct;49(10):1696-704.
907 Babich H, et al. In vitro cytotoxicity of (-)-catechin gallate, a minor polyphenol in green tea. Toxicol Lett. 2007 Jul 10;171(3):171-80.
908 J Med Chem 31:221 (1988); J Pharmacol Exp Ther 248:415 (1989)
909 Xiong Y, et al. Discovery and structure-activity relationship of 3-methoxy-N-(3-(1-methyl-1H-pyrazol-5-yl)-4-(2-morpholinoethoxy)phenyl)benzamide (APD791): a highly selective 5-hydroxytryptamine2A receptor inverse agonist for the treatment of arterial thrombosis. J Med Chem. 2010 Jun 10;53(11):4412-21.
910 Przyklenk K, et al. Targeted inhibition of the serotonin 5HT2A receptor improves coronary patency in an in vivo model of recurrent thrombosis. J Thromb Haemost. 2010 Feb;8(2):331-40.
911 Adams JW, et al. APD791, 3-methoxy-n-(3-(1-methyl-1h-pyrazol-5-yl)-4-(2-morpholinoethoxy)phenyl)benzamide, a novel 5-hydroxytryptamine 2A receptor antagonist: pharmacological profile, pharmacokinetics, platelet activity and vascular biology. J Pharmacol Exp Ther. 2009 Oct;331(1):96-103.
912 Sun X, et al. Structure-activity relationships of pyrrole based S-nitrosoglutathione reductase inhibitors: pyrrole regioisomers and propionic acid replacement. Bioorg Med Chem Lett. 2011 Jun 15;21(12):3671-5.
913 Colagiovanni DB, et al. A nonclinical safety and pharmacokinetic evaluation of N6022: a first-in-class S-nitrosoglutathione reductase inhibitor for the treatment of asthma. Regul Toxicol Pharmacol. 2012 Feb;62(1):115-24.
914 Green LS, et al. Mechanism of inhibition for N6022, a first-in-class drug targeting S-nitrosoglutathione reductase. Biochemistry. 2012 Mar 13;51(10):2157-68.
915 Thomas M. Raffay, et al. Methods of treating respiratory disorders. Patent. US 20170209419 A1.
916 Sakipova Z, et al. Quantification of santonin in eight species of &lt;i&gt;Artemisia&lt;/i&gt; from Kazakhstan by means of HPLC-UV: Method development and validation. PLoS One. 2017 Mar 16;12(3):e0173714. |J Chem Soc 1930:1110; Southern Med J 64:387 (1971); J Vet Pharmacol Therap 5:71 (1982); Jap J Parasit 34:325 (1985)
917 Hobl EL, et al. Tecarfarin: A Novel Vitamin K Antagonist. Thromb Haemost. 2017 Nov;117(11):2009-2011.
918 Bowersox SS, et al. Antithrombotic activity of the novel oral anticoagulant, Tecarfarin [Sodium 3-[4-((1,1,1,3,3,3-hexafluoro-2-methylpropan-2-yloxy) carbonyl) benzyl]-2-oxo-2H-chromen-4-olate] in animal models. Thromb Res. 2010 Nov;126(5):e383-8.
919 Kwon D, et al. Carbonyl cyanide 3-chlorophenylhydrazone (CCCP) suppresses STING-mediated DNA sensing pathway through inducing mitochondrial fission. Biochem Biophys Res Commun. 2017 Aug 30. pii: S0006-291X(17)31704-7.
920 Sinha D, et al. Synergistic efficacy of Bisbenzimidazole and Carbonyl Cyanide 3-Chlorophenylhydrazonecombination against MDR bacterial strains. Sci Rep. 2017 Mar 17;7:44419.
921 Kawamoto A, et al. Measurement of technetium-99m sestamibi signals in rats administered a mitochondrial uncoupler and in a rat model of heart failure. PLoS One. 2015 Jan 16;10(1):e0117091.
922 Kondapalli C, et al. PINK1 is activated by mitochondrial membrane potential depolarization and stimulates Parkin E3 ligase activity by phosphorylating Serine 65. Open Biol. 2012 May;2(5):120080.
923 Leesnitzer LM, et al. Functional consequences of cysteine modification in the ligand binding sites of peroxisome proliferator activated receptors by GW9662. Biochemistry. 2002 May 28;41(21):6640-50.
924 Seargent JM, et al. GW9662, a potent antagonist of PPARgamma, inhibits growth of breast tumor cells and promotes the anticancer effects of the PPARgamma agonist BRL 49653, independently of PPARgamma activation. Br J Pharmacol. 2004 Dec;143(8):933-7.
925 Sato K, et al. PPARγ antagonist attenuates mouse immune-mediated bone marrow failure by inhibition of T cell function.Haematologica. 2016 Jan;101(1):57-67.
926 Collino M, et al. The selective PPARgamma antagonist GW9662 reverses the protection of LPS in a model of renal ischemia-reperfusion. Kidney Int. 2005 Aug;68(2):529-36.
927 Du K, et al. Mito-tempo protects against acute liver injury but induces limited secondary apoptosis during the late phase of acetaminophen hepatotoxicity. Arch Toxicol. 2018 Oct 15.
928 Razzetti R, et al. Pharmacokinetic and pharmacologic properties of delapril, a lipophilic nonsulfhydryl angiotensin-converting enzyme inhibitor. Am J Cardiol. 1995 Jun 16;75(18):7F-12F.
929 Maria Anna Zipeto, et al. ADAR1 Activation Drives Leukemia Stem Cell Self-Renewal by Impairing Let-7 Biogenesis. Cell Stem Cell. 2016 Aug 4;19(2):177-191.
930 Rajagopal L, et al. GLYX-13 (rapastinel) ameliorates subchronic phencyclidine- and ketamine-induced declarative memory deficits in mice. Behav Brain Res. 2016 Feb 15;299:105-10.
931 Burgdorf J, et al. The long-lasting antidepressant effects of rapastinel (GLYX-13) are associated with a metaplasticity process in the medial prefrontal cortex and hippocampus. Neuroscience. 2015 Nov 12;308:202-11.
932 Eur J Biochem 51:329 (1975); J Clin Invest 72:1234 (1983)
933 Mathias Brault, et al. Plasma membrane depolarization induced by abscisic acid in Arabidopsis suspension cells involves reduction of proton pumping in addition to anion channel activation, which are both Ca&lt;sup&gt;2+&lt;/sup&gt; dependent. Plant Physiol. 2004 May;135(1):231-43.
934 Andrew Leber, et al. Abscisic acid enriched fig extract promotes insulin sensitivity by decreasing systemic inflammation and activating LANCL2 in skeletal muscle. Sci Rep. 2020 Jun 26;10(1):10463.
935 McKnight LE, et al. Structure-Based Discovery of a Novel Pentamidine-Related Inhibitor of the Calcium-Binding Protein S100B. ACS Med Chem Lett. 2012 Dec 13;3(12):975-979. Epub 2012 Sep 25.
936 Coonrod LA, et al. Reducing levels of toxic RNA with small molecules.ACS Chem Biol. 2013 Nov 15;8(11):2528-37.
937 Sharad K, et al. Identification of Potent, Selective, Cell-Active Inhibitors of the Histone Lysine Methyltransferase EZH2. ACS Med Chem Lett. 2012 Oct 19;3(12):1091-6.
938 Ding M, et al. The polycomb group protein enhancer of zeste 2 is a novel therapeutic target for cervical cancer. Clin Exp Pharmacol Physiol. 2015 May;42(5):458-64.
939 Teshima Y, et al. Cariporide (HOE642), a selective Na+-H+ exchange inhibitor, inhibits the mitochondrial death pathway. Circulation. 2003 Nov 4;108(18):2275-81.
940 Chang HB, et al. Na(+)/H(+) exchanger in the regulation of platelet activation and paradoxical effects of cariporide. Exp Neurol. 2015 Oct;272:11-6.
941 O'Donnell ME, et al. Intravenous HOE-642 reduces brain edema and Na uptake in the rat permanent middle cerebral artery occlusion model of stroke: evidence for participation of the blood-brain barrier Na/H exchanger. J Cereb Blood Flow Metab. 2013 Feb;33(2):225-34.
942 Marino MJ et al. Allosteric modulation of group III metabotropic glutamate receptor 4: a potential approach to Parkinson's disease treatment. Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13668-73.
943 Récasens M, et al. Metabotropic glutamate receptors as drug targets. Curr Drug Targets. 2007;8(5):651-681.
944 Clin. Ther. (2004), 26(9), 1355-1367; J. Pain Symptom Manage. (2004), 28(2), 140-175; Int. Congr. Symp. Ser. - R. Soc. Med. (2000), 245, 45-53
945 Phytochemistry 14:1829 (1975)
946 Neuropharmacology 21:803 (1982); Clin Neuropharmacol 8:1 (1985); Drugs 41:889 (1991)
947 May PC, et al. Robust central reduction of amyloid-β in humans with an orally available, non-peptidic β-secretase inhibitor. J Neurosci. 2011 Nov 16;31(46):16507-16516.
948 Zhang X, et al. Near-infrared fluorescence molecular imaging of amyloid beta species and monitoring therapy in animal models of Alzheimer's disease. Proc Natl Acad Sci U S A. 2015 Aug 4;112(31):9734-9.
949 Ghosh AK, et al. Prospects of β-Secretase Inhibitors for the Treatment of Alzheimer's Disease. ChemMedChem. 2015 Sep;10(9):1463-6
950 Filser S, et al. Pharmacological inhibition of BACE1 impairs synaptic plasticity and cognitive functions. Biol Psychiatry. 2015 Apr 15;77(8):729-39.
951 Mohamed AA, et al. Identification of a small molecule that selectively inhibits ERG-positive cancer cell growth. Cancer Res. 2018 Apr 30. pii: canres.2949.2017.
952 Cao G, et al. Ginsenoside Re reduces Aβ production by activating PPARγ to inhibit BACE1 in N2a/APP695 cells. Eur J Pharmacol. 2016 Dec 15;793:101-108.
953 Zhang Z, et al. Ginsenoside Re reduces insulin resistance through inhibition of c-Jun NH2-terminal kinase and nuclear factor-kappaB. Mol Endocrinol. 2008 Jan;22(1):186-95.
954 Su F, et al. Protective effect of ginsenosides Rg1 and Re on lipopolysaccharide-induced sepsis by competitive binding to Toll-like receptor 4. Antimicrob Agents Chemother. 2015 Sep;59(9):5654-63.
955 Fiskus W, et al. Highly effective combination of LSD1 (KDM1A) antagonist and pan-histone deacetylase inhibitor against human AML cells. Leukemia. 2014 Nov;28(11):2155-64.
956 Inui K, et al. Stepwise assembly of functional C-terminal REST/NRSF transcriptional repressor complexes as a drug target. Protein Sci. 2017 Feb 20
957 Sumalatha M, et al. Isoorientin, a Selective Inhibitor of Cyclooxygenase-2 (COX-2) from the Tubers of Pueraria tuberosa. Nat Prod Commun. 2015 Oct;10(10):1703-4.
958 Ye T, et al. Isoorientin induces apoptosis, decreases invasiveness, and downregulates VEGF secretion by activating AMPK signaling in pancreatic cancer cells. Onco Targets Ther. 2016 Dec 12;9:7481-7492.
959 Anilkumar K, et al. Evaluation of Anti-Inflammatory Properties of Isoorientin Isolated from Tubers of Pueraria tuberosa. Oxid Med Cell Longev. 2017;2017:5498054.
960 Toshiaki Sendo, et al. Carbazochrome sodium sulfonate (AC-17) reverses endothelial barrier dysfunction through inhibition of phosphatidylinositol hydrolysis in cultured porcine endothelial cells. Naunyn Schmiedebergs Arch Pharmacol. 2003 Sep;368(3):175-80.
961 Toshiaki Sendo, et al. Carbazochrome attenuates pulmonary dysfunction induced by a radiographic contrast medium in rats. Eur J Pharmacol. 2002 Aug 23;450(2):203-8.
962 Draper JM, et al. Discovery and evaluation of inhibitors of human ceramidase. Mol Cancer Ther. 2011 Nov;10(11):2052-61.
963 Kus G, et al. Induction of apoptosis in prostate cancer cells by the novel ceramidase inhibitor ceranib-2. In Vitro Cell Dev Biol Anim. 2015 Nov;51(10):1056-63.
964 https://clinicaltrials.gov/ct2/show/NCT04365517?term=Sitagliptin&cond=covid&draw=1&rank=2
965 https://clinicaltrials.gov/ct2/show/NCT04467931?term=Trandolapril&cond=COVID-19&draw=2&rank=2
966 https://clinicaltrials.gov/ct2/show/NCT04636034?term=Ropivacaine&cond=Covid19&draw=2&rank=1
967 Chen H, et al. Discovery of O-Alkylamino Tethered Niclosamide Derivatives as Potent and Orally Bioavailable Anticancer Agents. ACS Med Chem Lett. 2013 Feb 14;4(2):180-185.
968 Humphreys PG, et al. Discovery of a Potent, Cell Penetrant, and Selective p300/CBP-Associated Factor (PCAF)/General Control Nonderepressible 5 (GCN5) Bromodomain Chemical Probe. J Med Chem. 2017 Jan 26;60(2):695-709.
969 Gierse J, et al. A novel autotaxin inhibitor reduces lysophosphatidic acid levels in plasma and the site of inflammation. J Pharmacol Exp Ther. 2010 Jul;334(1):310-7.
970 Bhave SR, et al. Autotaxin Inhibition with PF-8380 Enhances the Radiosensitivity of Human and Murine Glioblastoma Cell Lines. Front Oncol. 2013 Sep 17;3:236.
971 Cao P, et al. Autocrine lysophosphatidic acid signaling activates β-catenin and promotes lung allograft fibrosis. J Clin Invest. 2017 Apr 3;127(4):1517-1530.
972 Takeda K, et al. Potentiation of Acetylcholine-Mediated Facilitation of Inhibitory Synaptic Transmission by an Azaindolizione Derivative, ZSET1446 (ST101), in the Rat Hippocampus. J Pharmacol Exp Ther. 2016 Feb;356(2):445-55
973 Yamaguchi Y, et al. Combination effects of ZSET1446/ST101 with memantine on cognitive function and extracellular acetylcholine in the hippocampus. J Pharmacol Sci. 2013;123(4):347-55. Epub 2013 Nov 29.
974 Yamaguchi Y, et al. Effects of ZSET1446/ST101 on cognitive deficits and amyloid β deposition in the senescence accelerated prone mouse brain. J Pharmacol Sci. 2012;119(2):160-6.
975 Helv Chim Acta 57: 1301 (1974); Tet Lett 3413 (1974); JACS 97: 6144 (1975); PNAS 98: 4788 (2001)
976 Cao G, et al. Ruscogenin Attenuates Cerebral Ischemia-Induced Blood-Brain Barrier Dysfunction by Suppressing TXNIP/NLRP3 Inflammasome Activation and the MAPK Pathway. Int J Mol Sci. 2016 Aug 29;17(9). pii: E1418.
977 Huang YL, et al. Possible mechanism of the anti-inflammatory activity of ruscogenin: role of intercellular adhesion molecule-1 and nuclear factor-kappaB. J Pharmacol Sci. 2008 Oct;108(2):198-205.
978 Row H, et al. HL271, a novel chemical compound derived from metformin, differs from metformin in its effects on the circadian clock and metabolism. Biochem Biophys Res Commun. 2016 Jan 15;469(3):783-9.
979 Bang E, et al. The Improving Effect of HL271, a Chemical Derivative of Metformin, a Popular Drug for Type II Diabetes Mellitus, on Aging-induced Cognitive Decline. Exp Neurobiol. 2018 Feb;27(1):45-56.
980 Sun Young Rha, et al. Phase I study of IM156, a novel potent biguanide oxidative phosphorylation (OXPHOS) inhibitor, in patients with advanced solid tumors. Journal of Clinical Oncology 38(15_suppl):3590-3590.
981 Arzneim Forsch 29:793, 1668 (1979); 30:73 (1980); Drugs 27:194 (1984)
982 Grygielko ET, et al. Inhibition of gene markers of fibrosis with a novel inhibitor of transforming growth factor-beta type I receptor kinase in puromycin-induced nephritis. J Pharmacol Exp Ther, 2005, 313(3), 943-951.
983 Thomas M, et al. ALK5 mediates abnormal proliferation of vascular smooth muscle cells from patients with familial pulmonary arterial hypertension and is involved in the progression of experimental pulmonary arterial hypertension induced by monocrotaline. Am J Pathol, 2009, 174(2), 380-389.
984 Laping NJ, et al. Tumor-specific efficacy of transforming growth factor-beta RI inhibition in Eker rats. Clin Cancer Res, 2007, 13(10), 3087-3899.
985 Mowbray CE, et al. Pyrazole NNRTIs 4: selection of UK-453,061 (lersivirine) as a development candidate. Bioorg Med Chem Lett. 2009 Oct 15;19(20):5857-60.
986 Gregg D Cappon, et al. Developmental toxicity study of lersivirine in mice. Birth Defects Res B Dev Reprod Toxicol. 2012 Jun;95(3):225-30.
987 Norman P. et al. A dual CCR2/CCR5 chemokine antagonist, BMS-813160? Evaluation of WO2011046916. Expert Opin Ther Pat. 2011 Dec;21(12):1919-24.
988 Misaki K, et al. Aryl hydrocarbon receptor ligand activity of polycyclic aromatic ketones and polycyclic aromatic quinones. Environ Toxicol Chem. 2007 Jul;26(7):1370-9.
989 Ruiz FX, et al. X-ray structure of the V301L aldo-keto reductase 1B10 complexed with NADP(+) and the potent aldose reductase inhibitor fidarestat: implications for inhibitor binding and selectivity. Chem Biol Interact. 2013 Feb 25;202(1-3):178-85.
990 Hotta N, et al. Effect of an aldose reductase inhibitor, SNK-860, on deficits in the electroretinogram of diabetic rats. Exp Physiol. 1995 Nov;80(6):981-9.
991 Boerma, M., et al. Comparative gene expression profiling in three primary human cell lines after treatment with a novel inhibitor of Rho kinase. Blood Coagul Fibrinolysis. 2008 Oct;19(7):709-18.
992 Lee, J.H., et al. Selective ROCK2 Inhibition In Focal Cerebral Ischemia. Ann Clin Transl Neurol. 2014 Jan 1;1(1):2-14.
993 https://clinicaltrials.gov/ct2/show/NCT04518735?term=WARFARIN&cond=covid&draw=2&rank=1
994 Umemori Y, et al. Evaluating the utility of N1,N12-diacetylspermine and N1,N8-diacetylspermidine in urine as tumormarkers for breast and colorectal cancers. Clin Chim Acta. 2010 Dec 14;411(23-24):1894-9.
995 Hiramatsu K, et al. Diagnostic and prognostic usefulness of N1,N8-diacetylspermidine and N1,N12-diacetylsperminein urine as novel markers of malignancy. J Cancer Res Clin Oncol. 1997;123(10):539-45
996 Proc. R. Soc. Med. (1971), 64(3), 243-9; Am. Surg. (1956), 22(12), 1225-32; Am. J. Dig. Dis. (1956), 1(11), 466-75
997 Keith B Pfister, et al. Heteroaryl compounds as kinase inhibitors. 2011, WO2011026917A1.
998 Donghang Cheng, et al. Small Molecule Regulators of Protein Arginine Methyltransferases. J Biol Chem. 2004 Jun 4;279(23):23892-9.
999 Zhang, B., et al. Targeting protein arginine methyltransferase 5 inhibits colorectal cancer growth by decreasing arginine methylation of eIF4E and FGFR3. Oncotarget. 2015 Sep 8;6(26):22799-811.
1000 Donghang Cheng, et al. Small Molecule Regulators of Protein Arginine Methyltransferases. J Biol Chem. 2004 Jun 4;279(23):23892-9.
1001 Baolai Zhang, et al. Arginine Methyltransferase inhibitor-1 Inhibits Sarcoma Viability in vitro and in vivo. Oncol Lett. 2018 Aug;16(2):2161-2166.
1002 Anesthesiology 11:606 (1950); Am J Health-System Pharm 54:388 (1997)
1003 Olivier Barret, et al. Adenosine 2A Receptor Occupancy by Tozadenant and Preladenant in Rhesus Monkeys. J Nucl Med. 2014 Oct;55(10):1712-8.
1004 https://clinicaltrials.gov/ct2/show/NCT04467931?term=LISINOPRIL&cond=Covid19&draw=2&rank=2
1005 https://clinicaltrials.gov/ct2/show/NCT04467931?term=AZILSARTAN&cond=COVID-19&draw=2&rank=1
1006 Acta Vet Scand 27:124 (1986); J Comp Pathol 97:21 (1987)
1007 Punit Saraon , et al. A Drug Discovery Platform to Identify Compounds That Inhibit EGFR Triple Mutants.Nat Chem Biol. 2020 May;16(5):577-586.
1008 JACS 81:2191 (1959)
1009 https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=ROSUVASTATIN+&cntry=&state=&city=&dist=&Search=Search
1010 Bamborough P, et al. Assessment of chemical coverage of kinome space and its implications for kinase drug discovery. J Med Chem. 2008 Dec 25;51(24):7898-914.
1011 Morgan BP, et al. Discovery of omecamtiv mecarbil the first, selective, small molecule activator of cardiac Myosin. ACS Med Chem Lett. 2010 Aug 20;1(9):472-7.
1012 Mamidi R, et al. Molecular effects of the myosin activator omecamtiv mecarbil on contractile properties of skinned myocardium lacking cardiac myosin binding protein-C. J Mol Cell Cardiol. 2015 Aug;85:262-72.
1013 Swenson AM, et al. Omecamtiv Mecarbil Enhances the Duty Ratio of Human β-Cardiac Myosin Resulting in Increased Calcium Sensitivity and Slowed Force Development in Cardiac Muscle. J Biol Chem. 2017 Mar 3;292(9):3768-3778.
1014 J. Pharmacol. Exp. Ther. (1982), 222(3), 645-51; J. Pharm. Pharmacol. (1971), 23(6), 407-11; J. Pharmacol. Exp. Ther. (1967), 155(1), 1-12
1015 Poncelet M, et al, Le Fur G. Antidepressant-like effects of SR 57227A, a 5-HT3 receptor agonist, in rodents. J Neural Transm Gen Sect. 1995;102(2):83‐90.
1016 Bachy A, et al. SR 57227A: a potent and selective agonist at central and peripheral 5-HT3 receptors in vitro and in vivo. Eur J Pharmacol. 1993;237(2-3):299‐309.
1017 Zhong S, et al. Identification and validation of human DNA ligase inhibitors using computer-aided drug design. J Med Chem. 2008 Aug 14;51(15):4553-4562.
1018 Chen X, et al. Rational design of human DNA ligase inhibitors that target cellular DNA replication and repair. Cancer Res. 2008 May 1;68(9):3169-3177.
1019 Oh S, et al. Antidiabetic and antiobesity effects of Ampkinone (6f), a novel small molecule activator of AMP-activated protein kinase. J Med Chem. 2010 Oct 28;53(20):7405-13.
1020 Kim SM, et al. Discovery of an Orally Bioavailable Gonadotropin-Releasing Hormone Receptor Antagonist. J Med Chem. 2016 Oct 13;59(19):9150-9172. Epub 2016 Sep 27.
1021 Chen C, et al. Discovery of sodium R-(+)-4-{2-[5-(2-fluoro-3-methoxyphenyl)-3-(2-fluoro-6-[trifluoromethyl]benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenylethylamino}butyrate (elagolix), a potent and orally available nonpeptide antagonist of the human gonadotropin-releasing hormone receptor. J Med Chem. 2008 Dec 11;51(23):7478-85.
1022 Bianchetti A, et al. In vitro inhibition of intestinal motility by phenylethanolaminotetralines: evidence of atypical beta-adrenoceptors in rat colon. Br J Pharmacol. 1990 Aug;100(4):831-9.
1023 Simiand J, et al. Antidepressant profile in rodents of SR 58611A, a new selective agonist for atypical beta-adrenoceptors. Eur J Pharmacol. 1992 Aug 25;219(2):193-201.
1024 Claustre Y, et al. Effects of the beta3-adrenoceptor (Adrb3) agonist SR58611A (amibegron) on serotonergic and noradrenergic transmission in the rodent: relevance to its antidepressant/anxiolytic-like profile. Neuroscience. 2008 Oct 2;156(2):353-64.
1025 Evans DM, et al. Exposure time versus cytotoxicity for anticancer agents.Cancer Chemother Pharmacol. 2019 Aug;84(2):359-371.
1026 Jung M, et al. Targeting BET bromodomains for cancer treatment. Epigenomics. 2015;7(3):487-501.
1027 Soejima R. Cefdinir. Jpn J Antibiot. 1992 Oct;45(10):1239-52.
1028 Labro MT, et al. Cefdinir (CI-983), a new oral amino-2-thiazolyl cephalosporin, inhibits human neutrophil myeloperoxidase in the extracellular medium but not the phagolysosome. J Immunol. 1994 Mar 1;152(5):2447-55. |Pediatr Infect Dis J 19:S141 (2000); 23:834 (2004); Drugs 64:1433 (2004)
1029 https://clinicaltrials.gov/ct2/show/NCT04834752?term=Lansoprazole&cond=covid&draw=2&rank=2
1030 J Parasitol 68:616 (1983); 70:446 (1984)|
1031 Amanda L Garner, et al. Design, synthesis, and biological activities of closantel analogues: structural promiscuity and its impact on Onchocerca volvulus. J Med Chem. 2011 Jun 9;54(11):3963-72.
1032 Amanda L Garner, et al. Design, synthesis, and biological activities of closantel analogues: structural promiscuity and its impact on Onchocerca volvulus. J Med Chem. 2011 Jun 9;54(11):3963-72.
1033 Protopopova M. IACS-10759: A novel OXPHOS inhibitor which selectively kill tumors with metabolic vulnerabilities. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4380. doi:10.1158/1538-7445.AM2015-4380
1034 Chen M, et al. Effect of monensin and lasalocid-sodium on the growth of methanogenic and rumen saccharolytic bacteria. Appl Environ Microbiol. 1979 Jul;38(1):72-7.
1035 Biochem J285:167 (1992); Br J Pharmacol 134:719 (2001); Mol Cancer Ther 6:1379 (2007)
1036 Arzneim Forsch 17:25 (1967)
1037 Purkey HE, et al. Cell Active Hydroxylactam Inhibitors of Human Lactate Dehydrogenase with Oral Bioavailability in Mice. ACS Med Chem Lett. 2016 Aug 26;7(10):896-901.
1038 Ždralević M, et al. Double genetic disruption of lactate dehydrogenases A and B is required to ablate the "Warburg effect" restricting tumor growth to oxidative metabolism. J Biol Chem. 2018 Oct 12;293(41):15947-15961.
1039 Ugolkov AV, et al. 9-ING-41, a small-molecule glycogen synthase kinase-3 inhibitor, is active in neuroblastoma. Anticancer Drugs. 2018 Sep;29(8):717-724.
1040 Wu X, et al. Targeting glycogen synthase kinase 3 for therapeutic benefit in lymphoma. Blood. 2019 Jul 25;134(4):363-373.
1041 Irina N Gaisina, et al. From a natural product lead to the identification of potent and selective benzofuran-3-yl-(indol-3-yl)maleimides as glycogen synthase kinase 3beta inhibitors that suppress proliferation and survival of pancreatic cancer cells. J Med Chem. 2009 Apr 9;52(7):1853-63.
1042 Hiroo Kuroki, et al. 9-ING-41, a small molecule inhibitor of GSK-3beta, potentiates the effects of anticancer therapeutics in bladder cancer. Sci Rep. 2019 Dec 27;9(1):19977.
1043 Kim MH, et al. Indirubin, a purple 3,2- bisindole, inhibited allergic contact dermatitis via regulating T helper (Th)-mediated immune system in DNCB-induced model. J Ethnopharmacol. 2013 Jan 9;145(1):214-9.
1044 Hsieh WL, et al. Indirubin, an acting component of indigo naturalis, inhibits EGFR activation and EGF-induced CDC25B gene expression in epidermal keratinocytes. J Dermatol Sci. 2012 Aug;67(2):140-6.
1045 Zhang X, et al. Indirubin inhibits tumor growth by antitumor angiogenesis via blocking VEGFR2-mediated JAK/STAT3 signaling in endothelial cell. Int J Cancer. 2011 Nov 15;129(10):2502-11.
1046 Alex D, et al. Indirubin shows anti-angiogenic activity in an in vivo zebrafish model and an in vitro HUVEC model. J Ethnopharmacol. 2010 Sep 15;131(2):242-7.
1047 https://clinicaltrials.gov/ct2/show/NCT04467931?term=Minoxidil&cond=covid&draw=2&rank=1
1048 3-Pyrimidin-4-yl-oxazolidin-2-ones as inhibitors of mutant IDH and their preparation. Patent WO 2013046136 A1 20130404
1049 Li H, et al. Morusin suppresses breast cancer cell growth in vitro and in vivo through C/EBPβ and PPARγ mediated lipoapoptosis. J Exp Clin Cancer Res. 2015 Nov 4;34:137.
1050 Lee JC, et al. Morusin induces apoptosis and suppresses NF-kappaB activity in human colorectal cancer HT-29 cells. Biochem Biophys Res Commun. 2008 Jul 18;372(1):236-42.
1051 Lim SL, et al. Morusin induces cell death through inactivating STAT3 signaling in prostate cancer cells. Am J Cancer Res. 2014 Dec 15;5(1):289-99.
1052 Goldstein DM et al. Discovery of 6-(2,4-difluorophenoxy)-2-[3-hydroxy-1-(2-hydroxyethyl)propylamino]-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one (pamapimod) and 6-(2,4-difluorophenoxy)-8-methyl-2-(tetrahydro-2H-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (R1487) as orally bioavailable and highly selective inhibitors of p38α mitogen-activated protein kinase. J Med Chem. 2011 Apr 14;54(7):2255-65.
1053 A Marchese, et al. In vitro activity of thiamphenicol against multiresistant Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus in Italy. J Chemother. 2002 Dec;14(6):554-61.
1054 Marta Tikhomirov, et al. Pharmacokinetics of florfenicol and thiamphenicol in ducks. J Vet Pharmacol Ther. 2019 Jan;42(1):116-120. |Br J Vener Dis 47:379 (1971); Antimicrob Agents Chemother 14:788 (1978); Int J Odontostomat 2:7 (2008)
1055 Li YZ,et al. Crotonoside exhibits selective post-inhibition effect in AML cells via inhibition of FLT3 and HDAC3/6. Oncotarget. 2017 Sep 8;8(61):103087-103099.
1056 Zhou B, et al. A small-molecule blocking ribonucleotide reductase holoenzyme formation inhibits cancer cell growth and overcomes drug resistance.Cancer Res. 2013 Nov 1;73(21):6484-93.
1057 Chen MC, et al. The Novel Ribonucleotide Reductase Inhibitor COH29 Inhibits DNA Repair In Vitro. Mol Pharmacol. 2015 Jun;87(6):996-1005.
1058 Yudao Shen, et al. Discovery of a First-in-Class Protein Arginine Methyltransferase 6 (PRMT6) Covalent Inhibitor. J Med Chem. 2020 May 28;63(10):5477-5487.
1059 Leclerc S, et al. Indirubins inhibit glycogen synthase kinase-3 beta and CDK5/p25, two protein kinases involved in abnormal tau phosphorylation in Alzheimer's disease. A property common to most cyclin-dependent kinase inhibitors? J Biol Chem. 2001 Jan 5;276(1):251-60.
1060 Rorick-Kehn LM, et al. LY2456302 is a novel, potent, orally-bioavailable small molecule kappa-selective antagonist with activity in animal models predictive of efficacy in mood and addictive disorders. Neuropharmacology. 2014 Feb;77:131-44.
1061 Jackson KJ, et al. Effects of orally-bioavailable short-acting kappa opioid receptor-selective antagonist LY2456302on nicotine withdrawal in mice. Neuropharmacology. 2015 Oct;97:270-4.
1062 Wu D, et al. Bidirectional modulation of HIF-2 activity through chemical ligands. Nat Chem Biol. 2019 Feb 25.
1063 Yue EW, et al. Discovery of potent competitive inhibitors of indoleamine 2,3-dioxygenase with in vivo pharmacodynamic activity and efficacy in a mouse melanoma model. J Med Chem. 2009 Dec 10;52(23):7364-7.
1064 Huang X, et al. Synthesis of [(18) F] 4-amino-N-(3-chloro-4-fluorophenyl)-N'-hydroxy-1,2,5-oxadiazole-3-carboximidamide (IDO5L): a novel potential PET probe for imaging of IDO1 expression. J Labelled Comp Radiopharm. 2015 Apr;58(4):156-62.
1065 Rahimian R, et al. Tropisetron attenuates amyloid-beta-induced inflammatory and apoptotic responses in rats. Eur J Clin Invest. 2013 Oct;43(10):1039-51.
1066 Swartz MM, et al. Tropisetron as a neuroprotective agent against glutamate-induced excitotoxicity and mechanisms of action. Neuropharmacology. 2013 Oct;73:111-21.
1067 Aminian A, et al. Tropisetron diminishes demyelination and disease severity in an animal model of multiple sclerosis. Neuroscience. 2013 Jun 15;248C:299-306.
1068 Rahimian R, et al. Tropisetron upregulates cannabinoid CB1 receptors in cerebellar granule cells: possible involvement of calcineurin. Brain Res. 2011 Oct 12;1417:1-8.
1069 Expert Opin Pharmacother 4:1157 (2003)
1070 J Pharmacol Exp Therap 81:116 (1944)
1071 Bodur E, et al. Inhibition effects of benactyzine and drofenine on human serum butyrylcholinesterase. Arch Biochem Biophys. 2001 Feb 1;386(1):25-9.
1072 Allikmets LH, et al. Dissimilar influences of imipramine, benactyzine and promazine on effects of micro-injections ofnoradrenaline, acetylcholine and serotonin into the amygdala in the cat. Psychopharmacologia. 1969;15(5):392-403.
1073 Brezak MC, et al. A novel synthetic inhibitor of CDC25 phosphatases: BN82002. Cancer Res. 2004 May 1;64(9):3320-5.
1074 Sha HH, et al. 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio) hexanol: a promising new anticancer compound. Biosci Rep. 2018 Feb 13;38(1). pii: BSR20171440.
1075 Filomeni G, et al. 6-(7-Nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol, a specific glutathione S-transferase inhibitor, overcomes the multidrug resistance (MDR)-associated protein 1-mediated MDR in small cell lung cancer. Mol Cancer Ther. 2008 Feb;7(2):371-9.
1076 Pellizzari Tregno F, et al. In vitro and in vivo efficacy of 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) on human melanoma. Eur J Cancer. 2009 Sep;45(14):2606-17.
1077 Yea CM, et al. New benzylureas as a novel series of potent, nonpeptidic vasopressin V2 receptor agonists. J Med Chem. 2008 Dec 25;51(24):8124-34.
1078 Eur J Pharmacol 10:131 (1970); Carcinogenesis 8:881 (1987)
1079 Wehn PM, et al. Design and Activity of Specific Hypoxia-Inducible Factor-2α (HIF-2α) Inhibitors for the Treatment of Clear Cell Renal Cell Carcinoma: Discovery of Clinical Candidate (S)-3-((2,2-Difluoro-1-hydroxy-7-(methylsulfonyl)-2,3-dihydro-1 H-inden-4-yl)oxy)-5-fluorobenzonitrile (PT2385). J Med Chem. 2018 Nov 8;61(21):9691-9721.
1080 Schmitt DM, et al. The use of resazurin as a novel antimicrobial agent against Francisella tularensis. Front Cell Infect Microbiol. 2013 Dec 6;3:93.
1081 Srimal RC,et al. Pharmacological studies on 2-(2-(4-(3-methylphenyl)-1-piperazinyl)ethyl) quinoline (centhaquin). I. Hypotensive activity.Pharmacol Res. 1990 May-Jun;22(3):319-29.
1082 Papalexopoulou K, et al. Centhaquin Effects in a Swine Model of Ventricular Fibrillation: Centhaquin and Cardiac Arrest.Heart Lung Circ. 2017 Aug;26(8):856-863.
1083 Antimicrob Agents Chemother 10:426 (1976); 19:625, 20:648 (1981)|
1084 Campoli-Richards DM, et al. Ceforanide. A review of its antibacterial activity, pharmacokinetic properties and clinical efficacy. Drugs. 1987 Oct;34(4):411-37.
1085 Myers JF, et al. Quantification of [11C]Ro15-4513 GABAAα5 specific binding and regional selectivity in humans. J Cereb Blood Flow Metab. 2016 Jul 27
1086 Zhang X, et al. Discovery of Novel Hepatitis B Virus Nucleocapsid Assembly Inhibitors. ACS Infect Dis. 2019 May 10;5(5):759-768.
1087 Wang P, et al. The Design and Synthesis of N-Xanthone Benzenesulfonamides as Novel Phosphoglycerate Mutase 1 (PGAM1) Inhibitors. Molecules. 2018 Jun 8;23(6). pii: E1396.
1088 Omar MA, et al. Utility of ninhydrin reagent for spectrofluorimetric determination of heptaminol in human plasma.Luminescence. 2018 Sep;33(6):1107-1112.
1089 Anantharaman S, et al. Ninhydrin-sodium molybdate chromogenic analytical probe for the assay of amino acids and proteins.rSpectrochim Acta A Mol Biomol Spectrosc. 2017 Feb 15;173:897-903.
1090 Medina-Rodríguez EM, et al. Promoting in vivo remyelination with small molecules: a neuroreparative pharmacological treatment for Multiple Sclerosis. Sci Rep. 2017 Mar 3;7:43545.
1091 Riendeau D, et al.Etoricoxib (MK-0663): preclinical profile and comparison with other agents that selectively inhibit cyclooxygenase-2. J Pharmacol Exp Ther. 2001 Feb;296(2):558-66.
1092 Kunak CS, et al. The Effect of Etoricoxib on Hepatic Ischemia-Reperfusion Injury in Rats. Oxid Med Cell Longev. 2015;2015:598162.
1093 Tanwar L, et al. Anti-proliferative and apoptotic effects of etoricoxib, a selective COX-2 inhibitor, on 1,2-dimethylhydrazine dihydrochloride-induced colon carcinogenesis. Asian Pac J Cancer Prev. 2010;11(5):1329-33.
1094 Attia RT, et al. The chemomodulatory effects of glufosfamide on docetaxel cytotoxicity in prostate cancer cells. PeerJ. 2016 Jun 29;4:e2168.
1095 Che CL, et al. DNA microarray reveals different pathways responding to NSC 125973 and docetaxel in non-small cell lung cancer cell line. Int J Clin Exp Pathol. 2013 Jul 15;6(8):1538-48.
1096 Obi-Ioka Y, et al. Involvement of Wee1 in the circadian rhythm dependent intestinal damage induced by docetaxel. J Pharmacol Exp Ther. 2013 Oct;347(1):242-8.
1097 Li C, et al. Non-linear pharmacokinetics of piperine and its herb-drug interactions with docetaxel in Sprague-Dawley rats. J Pharm Biomed Anal. 2016 Sep 5;128:286-93.
1098 Antimicrob Agents Chemother 11:852 (1977); 12:406 (1977); Lancet 1:620 (1980)
1099 Waaler J, et al. Novel synthetic antagonists of canonical Wnt signaling inhibit colorectal cancer cell growth. Cancer Res. 2011 Jan 1;71(1):197-205.
1100 Stratford EW, et al. The tankyrase-specific inhibitor JW74 affects cell cycle progression and induces apoptosis and differentiation in osteosarcoma cell lines. Cancer Med. 2014 Feb;3(1):36-46.
1101 Clin Toxicol 4:185 (1971); Drug Saf 28:89 (2005)
1102 Kim JW, et al. Triterpenoid Saponins Isolated from Platycodon grandiflorum Inhibit Hepatitis C Virus Replication. Evid Based Complement Alternat Med. 2013;2013:560417.
1103 Wang L, et al. Characterization of a Steroid Receptor Coactivator Small Molecule Stimulator that Overstimulates Cancer Cells and Leads to Cell Stress and Death. Cancer Cell. 2015 Aug 10;28(2):240-52.
1104 Biochem Pharmacol 65:1741 (2003)
1105 Yu W, et al. Cyclosporine A Suppressed Glucose Oxidase Induced P53 Mitochondrial Translocation and Hepatic Cell Apoptosis through Blocking Mitochondrial Permeability Transition. Int J Biol Sci. 2016 Jan 1;12(2):198-209.
1106 Hoagland MS, et al. The p53 Inhibitor Pifithrin-α Is a Potent Agonist of the Aryl Hydrocarbon Receptor. J Pharmacol Exp Ther. 2005 Aug;314(2):603-10.
1107 Kuang SQ, et al. FOXE3 mutations predispose to thoracic aortic aneurysms and dissections. J Clin Invest. 2016 Mar 1;126(3):948-61.
1108 Ding YH, et al. Increasing the Depth of Mass-Spectrometry-Based Structural Analysis of Protein Complexes through the Use of Multiple Cross-Linkers. Anal Chem. 2016 Apr 19;88(8):4461-9.
1109 De Miranda BR, et al. The Nurr1 Activator 1,1-Bis(3'-Indolyl)-1-(p-Chlorophenyl)Methane Blocks Inflammatory Gene Expression in BV-2 Microglial Cells by Inhibiting Nuclear Factor κB. Mol Pharmacol. 2015 Jun;87(6):1021-34. doi: 10.1124/mol.114.095398. Epub 2015 Apr 9.
1110 Hammond SL, et al. A novel synthetic activator of Nurr1 induces dopaminergic gene expression and protects against 6-hydroxydopamine neurotoxicity in vitro. Neurosci Lett. 2015 Oct 21;607:83-9.
1111 Zheng J, et al. para-Aminosalicylic acid is a prodrug targeting dihydrofolate reductase in Mycobacterium tuberculosis. J Biol Chem. 2013 Aug 9;288(32):23447-56.
1112 Sy SK, et al. N-acetyltransferase genotypes and the pharmacokinetics and tolerability of para-aminosalicylic acid in drug-resistant pulmonary tuberculosis patients. Antimicrob Agents Chemother. 2015 May 11. pii: AAC.04049-14.
1113 J Pharm Exp Therap 49:50 (1933); Ann Surg 103:535 (1936)
1114 Jean R. Rapin, et al. In vitro and in vivo effects of an extract of Ginkgo biloba (EGb 761), ginkgolide B, and bilobalide on apoptosis in primary cultures of rat hippocampal neurons. Drug Development Research, 1998, 45 (1):1-43
1115 Matyas Koltai, et al. Ginkgolide B protects isolated hearts against arrhythmias induced by ischemia but not reperfusion. European Journal of Pharmacology, 1989, 164 (2): 293-302
1116 Am J Therapeutics 4:159 (1997); Pharmacotherapy 26:748 (2006)
1117 Sehon CA, et al. Potent, selective and orally bioavailable dihydropyrimidine inhibitors of Rho kinase (ROCK1) as potential therapeutic agents for cardiovascular diseases. J Med Chem. 2008 Nov 13;51(21):6631-4.
1118 https://clinicaltrials.gov/ct2/show/NCT04738045?term=Lopinavir&recrs=abdef&cond=Covid19&draw=2&rank=1
1119 Chen JK, et al. Small molecule modulation of Smoothened activity. Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14071-6.
1120 Stanton BZ, et al. A small molecule that binds Hedgehog and blocks its signaling in human cells. Nat Chem Biol. 2009 Mar;5(3):154-6.
1121 Lee S, et al. Combining Smoothened Agonist (SAG) and NEL-like protein-1 (NELL-1) Enhances Bone Healing. Plast Reconstr Surg. 2017 Feb 13
1122 Fish EW, et al. Preaxial polydactyly following early gestational exposure to the smoothened agonist, SAG, in C57BL/6J mice. Birth Defects Res A Clin Mol Teratol. 2016 Nov 1
1123 Guerrini G, et, al. Inhibition of smoothened in breast cancer cells reduces CAXII expression and cell migration. J Cell Physiol. 2018 Dec; 233(12): 9799-9811.
1124 Pharmacol Toxicol USSR 54: 35 (1991); J Gen Chem 33: 2663 (1963)
1125 Cersosimo RJ, et al. Epirubicin: a review of the pharmacology, clinical activity, and adverse effects of an adriamycin analogue. J Clin Oncol. 1986 Mar;4(3):425-39.
1126 Ozkan, A., et al. Epirubicin HCl toxicity in human-liver derived hepatoma G2 cells. Pol J Pharmacol, 2004. 56(4): p. 435-44.
1127 Bonadonna, G., et al. Drugs ten years later: epirubicin. Ann Oncol, 1993. 4(5): p. 359-69.
1128 Asanuma, F., et al. Antitumor activity of paclitaxel and epirubicin in human breast carcinoma, R-27. Folia Microbiol (Praha), 1998. 43(5): p. 473-4.
1129 Kashima H, et al. Epirubicin, Identified Using a Novel Luciferase Reporter Assay for Foxp3 Inhibitors, Inhibits Regulatory T Cell Activity. PLoS One. 2016 Jun 10;11(6):e0156643.
1130 Drugs 35:143 (1988); J Am Acad Dermatol 21:686 (1989)
1131 https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=QUININE&cntry=&state=&city=&dist=&Search=Search
1132 Schiedel M, et al. Structure-Based Development of an Affinity Probe for Sirtuin 2. Angew Chem Int Ed Engl. 2016 Feb 5;55(6):2252-6.
1133 Drugs (1978), 15(1), 33-52; Arzneim. Forsch. (1974), 24(10), 1633-6; J. Med. Chem. (1973), 16(7), 782-6
1134 Schepetkin IA, et al. Identification and characterization of a novel class of c-Jun N-terminal kinase inhibitors. Mol Pharmacol. 2012 Jun;81(6):832-45.
1135 Ji-Hye Kim, et al. Identification of a Novel SIRT7 Inhibitor as Anticancer Drug Candidate. Biochem Biophys Res Commun. 2019 Jan 8;508(2):451-457.
1136 Kozhikhova KV, et al. Preparation of chitosan-coated liposomes as a novel carrier system for the antiviral drug Triazavirin. Pharm Dev Technol. 2018 Apr;23(4):334-342.
1137 Loginova SIa, et al. Investigation of Triazavirin antiviral activity against tick-borne encephalitis pathogen in cell culture. Antibiot Khimioter. 2014;59(1-2):3-5.
1138 Loginova SY, et al. Investigation of Therapeutic Efficacy of Triazavirin Against Experimental Forest-Spring Encephalitis on Albino Mice. Antibiot Khimioter. 2015;60(7-8):11-3.
1139 Kyla. A. L. Collins, et al. Proteomic Analysis Defines Kinase Taxonomies Specific for Subtypes of Breast Cancer. Apr. 1, 2017.
1140 Felix S. Oppermann, et al. Large-scale Proteomics Analysis of the Human Kinome. Mol Cell Proteomics. 2009 Jul; 8(7): 1751-1764.
1141 Antimicrob Agents Chemother 13:784 (1978); 21:344 (1982)
1142 Zeitlin BD, et al. Antiangiogenic effect of TW37, a small-molecule inhibitor of Bcl-2. Cancer Res. 2006 Sep 1;66(17):8698-706.
1143 Mohammad RM, et al. Preclinical studies of TW-37, a new nonpeptidic small-molecule inhibitor of Bcl-2, in diffuse large cell lymphoma xenograft model reveal drug action on both Bcl-2 and Mcl-1. Clin Cancer Res. 2007 Apr 1;13(7):2226-35.
1144 van Breemen RB, et al. Cyclooxygenase-2 inhibitors in ginger (Zingiber officinale). Fitoterapia. 2011 Jan;82(1):38-43.
1145 Keum YS, et al. Induction of apoptosis and caspase-3 activation by chemopreventive
1146 -paradol and structurally related compounds in KB cells. Cancer Lett. 2002 Mar 8;177(1):41-7.
1147 Gaire BP, et al. Neuroprotective effect of 6-paradol in focal cerebral ischemia involves the attenuation of neuroinflammatory responses in activated microglia. PLoS One. 2015 Mar 19;10(3):e0120203.
1148 Setoguchi S, et al. Pharmacokinetics of Paradol Analogues Orally Administered to Rats. J Agric Food Chem. 2016 Mar 9;64(9):1932-7.
1149 Battram, C., et al., In vitro and in vivo pharmacological characterization of 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-1H-quinolin-2-o ne (indacaterol), a novel inhaled beta(2) adrenoceptor agonist with a 24-h duration of action. J Pharmacol Exp Ther, 2006. 317(2): p. 762-70.
1150 Sturton, R.G., et al., Pharmacological characterization of indacaterol, a novel once daily inhaled 2 adrenoceptor agonist, on small airways in human and rat precision-cut lung slices. J Pharmacol Exp Ther, 2008. 324(1): p. 270-5.
1151 Shinichi Oda*, et al. Development of an Optimized Synthetic and Purification Process of S-2367 (Velneperit), a Novel Neuropeptide Y (NPY) Y5 Receptor Antagonist. Org. Process Res. Dev., 2015, 19 (4), pp 531-536.
1152 Jon E Hawkinson, et al. Potent Pyrimidine and Pyrrolopyrimidine Inhibitors of Testis-Specific Serine/Threonine Kinase 2 (TSSK2). ChemMedChem. 2017 Nov 22;12(22):1857-1865.
1153 Peterson L.G. Tricyclazole for Control of Pyricularia Oryzae on Rice: the Relationship of the Mode of Action and Disease Occurrence and Development. Pest Management in Rice. Springer, Dordrecht.
1154 G.Lazarovits, et al. Tricyclazole induces melanin shunt products and inhibits altersolanol a accumulation by Alternaria solani. Pesticide Biochemistry and Physiology
1155 J Am Chem Soc 71: 4158 (1955); Nature Medicine 16:279 (2010); Proc Natl Acad Sci 107:19961 (2010)
1156 Flaveny CA, et al. Broad Anti-tumor Activity of a Small Molecule that Selectively Targets the Warburg Effect and Lipogenesis. Cancer Cell. 2015 Jun 24. pii: S1535-6108(15)00183-X.
1157 Smith SM, et al. The novel phosphodiesterase 10A inhibitor THPP-1 has antipsychotic-like effects in rat and improves cognition in rat and rhesus monkey. Neuropharmacology. 2013 Jan;64:215-23.
1158 Vardigan JD, et al. Behavioral and qEEG effects of the PDE10A inhibitor THPP-1 in a novel rhesus model of antipsychotic activity. Psychopharmacology (Berl). 2016 Jul;233(13):2441-50.
1159 Xie CI, et al. Daidzin, an antioxidant isoflavonoid, decreases blood alcohol levels and shortens sleep time induced by ethanol intoxication. Alcohol Clin Exp Res. 1994 Dec;18(6):1443-7.
1160 Keung WM, et al. Kudzu root: an ancient Chinese source of modern antidipsotropic agents. Phytochemistry. 1998 Feb;47(4):499-506.
1161 Keung WM, et al. Daidzin inhibits mitochondrial aldehyde dehydrogenase and suppresses ethanol intake of Syrian golden hamsters. Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1675-9.
1162 Moon TC, et al. A new class of COX-2 inhibitor, rutaecarpine from Evodia rutaecarpa. Inflamm Res. 1999 Dec;48(12):621-5.
1163 Lee SH, et al. Progress in the studies on rutaecarpine. Molecules. 2008 Feb 6;13(2):272-300.
1164 Jeon TW, et al. Immunosuppressive effects of rutaecarpine in female BALB/c mice.&#x0D; Toxicol Lett. 2006 Jul 1;164(2):155-66.
1165 Ke Y, et al. Scutellarin suppresses migration and invasion of human hepatocellular carcinoma by inhibiting the STAT3/Girdin/Akt activity. Biochem Biophys Res Commun. 2016 Dec 18. pii: S0006-291X(16)32174-X
1166 Yang LL, et al. Differential regulation of baicalin and scutellarin on AMPK and Akt in promoting adipose cell glucose disposal. Biochim Biophys Acta. 2016 Nov 27;1863(2):598-606.
1167 Wu CY, et al. Scutellarin attenuates microglia-mediated neuroinflammation and promotes astrogliosis in cerebral ischemia - a therapeutic consideration. Curr Med Chem. 2016 Nov 18. [Epub ahead of print]
1168 Li Q, et al. Scutellarin attenuates vasospasm through the Erk5-KLF2-eNOS pathway after subarachnoid hemorrhage in rats. J Clin Neurosci. 2016 Dec;34:264-270
1169 Zhao S, et al. Scutellarin inhibits RANKL-mediated osteoclastogenesis and titanium particle-induced osteolysis via suppression of NF-κB and MAPK signaling pathway. Int Immunopharmacol. 2016 Nov;40:458-465
1170 Zhang GH, et al. The anti-HIV-1 effect of scutellarin. Biochem Biophys Res Commun. 2005 Sep 2;334(3):812-6.
1171 Guagnano V, et al. Discovery of 3-(2,6-Dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-me thyl-urea (NVP-BGJ398), A Potent and Selective Inhibitor of the Fibroblast Growth Factor Receptor Family of Receptor T
1172 Konecny GE, et al. Activity of the fibroblast growth factor receptor inhibitors dovitinib (TKI258) and NVP-BGJ398 in human endometrial cancer cells. Mol Cancer Ther. 2013 May;12(5):632-42.
1173 Liu H, et al. Identifying and Targeting Sporadic Oncogenic Genetic Aberrations in Mouse Models of Triple Negative Breast Cancer. Cancer Discov. 2018 Mar;8(3):354-369.
1174 Li Y, et al. In vitro assessment of metabolic drug–drug interaction potential of AZD2624, neurokinin-3 receptor antagonist, through cytochrome P(450) enzyme identification, inhibition, and induction studies. Xenobiotica. 2010 Nov;40(11):721-9.
1175 Kasibhatla S, et al. MPC-6827: a small-molecule inhibitor of microtubule formation that is not a substrate for multidrug resistance pumps. Cancer Res. 2007 Jun 15;67(12):5865-71.
1176 San José-Enériz E, et al. Discovery of first-in-class reversible dual small molecule inhibitors against G9a and DNMTs in hematological malignancies. Nat Commun. 2017 May 26;8:15424.
1177 Miyachi H, et al. Synthesis and antimuscarinic activity of a series of 4-(1-Imidazolyl)-2,2-diphenylbutyramides: discovery of potent and subtype-selective antimuscarinic agents. Bioorg Med Chem. 1999 Jun;7(6):1151-61.
1178 Yamazaki T, et al. Imidafenacin has no influence on learning in nucleus basalis of Meynert-lesioned rats. Naunyn Schmiedebergs Arch Pharmacol. 2013 Dec;386(12):1095-102.
1179 Luo Z, et al. Epigoitrin, an Alkaloid From Isatis indigotica, Reduces H1N1 Infection in Stress-Induced Susceptible Model in vivo and in vitro. Front Pharmacol. 2019 Feb 7;10:78.
1180 Xiao P, et al. Antiviral activities against influenza virus (FM1) of bioactive fractions and representative compounds extracted from Banlangen (Radix Isatidis). J Tradit Chin Med. 2016 Jun;36(3):369-76.
1181 Psychopharmacologica 12:142 (1968); Anal Profiles Drug Subs 18:527 (1989)
1182 JACS 47:2727 (1925); J Chromatography 39: 182 (1969); Am Rev Respir Dis 111:703 (1975); Tubercle 59:135 (1978)
1183 https://clinicaltrials.gov/ct2/show/NCT04348305?term=Hydrocortisone&cond=COVID-19&draw=2&rank=1 https://clinicaltrials.gov/ct2/show/NCT04456439?term=Hydrocortisone&cond=COVID-19&draw=2&rank=6 https://clinicaltrials.gov/ct2/show/NCT02735707?term=Hydrocortisone&cond=COVID-19&draw=2&rank=8 https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20120215009014N354 https://trialsearch.who.int/Trial2.aspx?TrialID=ISRCTN67000769 https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20120215009014N354 https://trialsearch.who.int/Trial2.aspx?TrialID=NCT02517489 https://trialsearch.who.int/Trial2.aspx?TrialID=NCT04348305
1184 Abd-Alla, H. I.,et al. New bioactive compounds from &lt;i&gt;Aloe hijazensis&lt;/i&gt;. Natural Product Research,2009,23(11), 1035–1049.
1185 Drugs 29:531 (1985); Am Heart J 109:1211 (1985)
1186 Biochem J 5:243 (1911); J Physiol 45:1 (1914); Acta Pharmacol Toxicol 10:338 (1954)
1187 Br J Opthalmol77:136 (1993); J Wilderness Med 5:34 (1994)
1188 Atta-ur-Rahman, et al. Bioactive constituents from Boswellia papyrifera. J Nat Prod. 2005 Feb;68(2):189-93.
1189 Wu TT, et al. β-Elemonic acid inhibits the cell proliferation of human lung adenocarcinoma A549 cells: The roleof MAPK, ROS activation and glutathione depletion. Oncol Rep. 2016 Jan;35(1):227-34.
1190 Kim YS, et al. Isolation of a new saponin and cytotoxic effect of saponins from the root of Platycodon grandiflorum on human tumor cell lines. Planta Med. 2005 Jun;71(6):566-8.
1191 Lain S, et al. Discovery, in vivo activity, and mechanism of action of a small-molecule p53 activator. Cancer Cell. 2008 May;13(5):454-63.
1192 Jifei Miao, et al. Nuclear HMGB1 promotes the phagocytic ability of macrophages. Exp Cell Res. 2020 Aug 1;393(1):112037.
1193 https://clinicaltrials.gov/ct2/show/NCT04978051?term=Icatibant&cond=COVID-19&draw=2&rank=1
1194 Evelyn CR, et al. Design, synthesis and prostate cancer cell-based studies of analogs of the Rho/MKL1 transcriptional pathway inhibitor, CCG-1423. Bioorg Med Chem Lett. 2010 Jan 15;20(2):665-72.
1195 Jin W, et al. Increased SRF transcriptional activity in human and mouse skeletal muscle is a signature of insulin resistance. J Clin Invest. 2011 Mar;121(3):918-29.
1196 Chong NW, et al. STARS is essential to maintain cardiac development and function in vivo via a SRF pathway. PLoS One. 2012;7(7):e40966.
1197 Duggirala A, et al. cAMP-induced actin cytoskeleton remodelling inhibits MKL1-dependent expression of the chemotactic and pro-proliferative factor, CCN1. J Mol Cell Cardiol. 2014 Nov 18;79C:157-168.
1198 Sharma VK, et al. Chemoenzymatic convergent synthesis of 2'-O,4'-C-methyleneribonucleosides. J Org Chem. 2014 Jul 3;79(13):6336-41.
1199 Marek L, et al. Histone deacetylase (HDAC) inhibitors with a novel connecting unit linker region reveal a selectivity profile for HDAC4 and HDAC5 with improved activity against chemoresistant cancer cells. J Med Chem. 2013 Jan 24;56(2):427-36.
1200 Li A, et al. HDAC5, a potential therapeutic target and prognostic biomarker, promotes proliferation, invasion and migration in human breast cancer. Oncotarget. 2016 Jun 21;7(25):37966-37978.
1201 Trazzi S, et al. HDAC4: a key factor underlying brain developmental alterations in CDKL5 disorder. Hum Mol Genet. 2016 Sep 15;25(18):3887-3907.
1202 J Chem Soc 87:145 (1905); J Soc Chem Ind 37:288 (1918)|
1203 Nihal Doğruöz Güngör, et al. Evaluation of bacterial resistance to Chloramine T Biocide and effects on Rifampicin Antibiotic Susceptibility as a consequence of biocide usage in Cooling System Biofilm including Legionella pneumophila. The Battle Against Microbial Pathogens: Basic Science, Technological Advances and Educational Programs.
1204 J. Int. Med. Res. (1981), 9(1), 79-81; Science (1977), 197(4307), 994-6; J. Int. Med. Res. (1976), 4(6), 454-61
1205 Borroto A, et al. First-in-class inhibitor of the T cell receptor for the treatment of autoimmune diseases. Sci Transl Med. 2016 Dec 21;8(370):370ra184.
1206 Kang MS, et al. Inhibitory effect of methyl gallate and gallic acid on oral bacteria. J Microbiol. 2008 Dec;46(6):744-50.
1207 Hsieh TJ, et al. Protective effect of methyl gallate from Toona sinensis (Meliaceae) against hydrogen peroxide-induced oxidative stress and DNA damage in MDCK cells. Food Chem Toxicol. 2004 May;42(5):843-50.
1208 Lee H, et al. Methyl gallate exhibits potent antitumor activities by inhibiting tumor infiltration of CD4+CD25+ regulatory T cells. J Immunol. 2010 Dec 1;185(11):6698-705.
1209 Wang CR, et al. First report on isolation of methyl gallate with antioxidant, anti-HIV-1 and HIV-1 enzyme inhibitory activities from a mushroom (Pholiota adiposa). Environ Toxicol Pharmacol. 2014 Mar;37(2):626-37.
1210 Warner Lambert, et al. Some Neurochemical Properties of Pramiracetam (CI-879), A New Cognition-Enhancing Agent.
1211 Chang T, et al. Pharmacokinetics of oral pramiracetam in normal volunteers. J Clin Pharmacol. 1985 May-Jun;25(4):291-5.
1212 Deng C, et al. The novel IKK2 inhibitor LY2409881 potently synergizes with histone deacetylase inhibitors in preclinical models of lymphoma through the downregulation of NF-κB. Clin Cancer Res. 2015 Jan 1;21(1):134-45.
1213 Mahajan S, et al. Rational design and synthesis of a novel anti-leukemic agent targeting Bruton's tyrosine kinase (BTK), LFM-A13 [alpha-cyano-beta-hydroxy-beta-methyl-N-(2, 5-dibromophenyl)propenamide]. J Biol Chem. 1999 Apr 2;274(14):9587-99.
1214 van den Akker E, et al. The Btk inhibitor LFM-A13 is a potent inhibitor of Jak2 kinase activity. Biol Chem. 2004 May;385(5):409-13.
1215 "Sahin K, et al. LFM-A13, a potent inhibitor of polo-like kinase, inhibits breast carcinogenesis by suppressing proliferation activity and inducing apoptosis in breast tumors of mice. Invest New Drugs. 2017 Nov 15. "
1216 Uckun FM, et al. Anti-breast cancer activity of LFM-A13, a potent inhibitor of Polo-like kinase (PLK). Bioorg Med Chem. 2007 Jan 15;15(2):800-14. Epub 2006 Oct 26.
1217 Ocasio CA, et al. A first generation inhibitor of human Greatwall kinase, enabled by structural and functional characterisation of a minimal kinase domain construct. Oncotarget. 2016 Nov 1;7(44):71182-71197.
1218 J Biol Chem 267:8123 (!992); J Lab Clin Med 143:143 (2004)
1219 Ber 56: 2556 (1923); JACS 88: 2053 (1966); Tetrahedron 24: 2707 (1968); J Chem Soc 1984: 1035,1043
1220 Zhang T, et al. Discovery of Potent and Selective Covalent Inhibitors of JNK. Chem Biol. 2012 Jan 27;19(1):140-54.
1221 Wu W, et al. Divalent metal-ion transporter 1 is decreased in intestinal epithelial cells and contributes to the anemia in inflammatory bowel disease. Sci Rep. 2015 Nov 17;5:16344.
1222 J Pharmacol Exp Ther 275: 864 (1995)
1223 Adv Biochem Psychopharmacol 35:163 (1982); Drugs 25:451 (1983)
1224 Weiwen Liu, et al. Antitumor Activity and Mechanism of a Reverse Transcriptase Inhibitor, Dapivirine, in Glioblastoma. J Cancer. 2018 Jan 1;9(1):117-128.
1225 Bríd Devlin, et al. Development of dapivirine vaginal ring for HIV prevention. Antiviral Res. 2013 Dec;100 Suppl:S3-8.
1226 Yven Van Herrewege, et al. In vitro evaluation of nonnucleoside reverse transcriptase inhibitors UC-781 and TMC120-R147681 as human immunodeficiency virus microbicides. Antimicrob Agents Chemother. 2004 Jan;48(1):337-9.
1227 Michael E Halwes, et al. Pharmacokinetic modeling of a gel-delivered dapivirine microbicide in humans. Eur J Pharm Sci. 2016 Oct 10;93:410-8.
1228 Peter S, et al. Tumor cell-specific inhibition of MYC function using small molecule inhibitors of the HUWE1 ubiquitin ligase. EMBO Mol Med. 2014 Dec;6(12):1525-41.
1229 Zhang, Qiang; Ma, Peng; Cole, Richard B.; Wang, Guangdi In vitro metabolism of indomethacin morpholinylamide (BML-190), an inverse agonist for the peripheral cannabinoid receptor (CB2) in rat liver microsomes. European Journal of Pharmaceutical Sciences (2010), 41(1), 163-172.
1230 Klegeris, Andis; Bissonnette, Christopher J.; McGeer, Patrick L. Reduction of human monocytic cell neurotoxicity and cytokine secretion by ligands of the cannabinoid-type CB2 receptor. British Journal of Pharmacology (2003), 139(4), 775-786.
1231 New DC, Wong YH. BML-190 and AM251 act as inverse agonists at the human cannabinoid CB2 receptor: signalling via cAMP and inositol phosphates. FEBS Lett. 2003 Feb 11;536(1-3):157-60.
1232 Lyons ET, et, al. Haloxon: critical tests of antiparasitic activity in equids. Am J Vet Res. 1981 Jun;42(6):1043-5.
1233 Hart RJ, et, al. Cholinesterase activities of various nematode parasites and their inhibition by the organophosphate anthelmintic haloxon. Exp Parasitol. 1966 Jun;18(3):332-7.
1234 Tria GS, et al. Discovery of LSZ102, a Potent, Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen Receptor Positive Breast Cancer. J Med Chem. 2018 Apr 12;61(7):2837-2864.
1235 Zeng Z, et al. Arnebin-1 promotes angiogenesis by inducing eNOS, VEGF and HIF-1α expression through the PI3K-dependent pathway. Int J Mol Med. 2015 Sep;36(3):685-97.
1236 Sidhu GS, et al. Arnebin-1 accelerates normal and hydrocortisone-induced impaired wound healing. J Invest Dermatol. 1999 Nov;113(5):773-81.
1237 Arzneim Forsch 28:586. 605 (1978)|
1238 Michaelis M, et al. Identification of flubendazole as potential anti-neuroblastoma compound in a large cell line screen. Sci Rep. 2015 Feb 3;5:8202.
1239 Zhou X, et al. Flubendazole inhibits glioma proliferation by G2/M cell cycle arrest and pro-apoptosis. Cell Death Discov. 2018 Feb 14;4:18.
1240 Heil F, et al. The Toll-like receptor 7 (TLR7)-specific stimulus loxoribine uncovers a strong relationship within the TLR7, 8 and 9 subfamily. Eur J Immunol. 2003 Nov;33(11):2987-97.
1241 Dzopalic T, et al. Loxoribine, a selective Toll-like receptor 7 agonist, induces maturation of human monocyte-derived dendritic cells and stimulates their Th-1- and Th-17-polarizing capability. Int Immunopharmacol. 2010 Nov;10(11):1428-33.
1242 Pope BL, et al. In vivo enhancement of murine natural killer cell activity by 7-allyl-8-oxoguanosine (loxoribine). Int J Immunopharmacol. 1992 Nov;14(8):1375-82.
1243 Liu T, et al. Synthetic silvestrol analogues as potent and selective protein synthesis inhibitors. J Med Chem. 2012 Oct 25;55(20):8859-78.
1244 Lawrence NJ, et al. Cytotoxic Michael-type amine adducts of alpha-methylene lactones alantolactone and isoalantolactone. Bioorg Med Chem Lett. 2001 Feb 12;11(3):429-31.
1245 Khan M, et al. Isoalantolactone induces reactive oxygen species mediated apoptosis in pancreatic carcinoma PANC-1 cells. Int J Biol Sci. 2012;8(4):533-47.
1246 Blake JF, et al. Discovery and preclinical pharmacology of a selective ATP-competitive Akt inhibitor (GDC-0068) for the treatment of human tumors. J Med Chem. 2012 Sep 27;55(18):8110-27.
1247 Lin J, et al. Targeting activated Akt with GDC-0068, a novel selective Akt inhibitor that is efficacious in multiple tumor models. Clin Cancer Res. 2013 Apr 1;19(7):1760-72.
1248 Laraia L, et al. The cholesterol transfer protein GRAMD1A regulates autophagosome biogenesis. Nat Chem Biol. 2019 Jul;15(7):710-720.
1249 Acta Anaeth Scand 34:595 (1990); Chest c103:771 (1993)
1250 Liang QL, et al. [Structure modification on sesquiterpene lactones from Elephantopus scaber]. Yao Xue Xue Bao. 2007 Nov;42(11):1159-61.
1251 Hiradeve SM, et al. A review on pharmacology and toxicology of Elephantopus scaber Linn. Nat Prod Res. 2014;28(11):819-30.
1252 Spencer AG, et al. Intestinal inhibition of the Na+/H+ exchanger 3 prevents cardiorenal damage in rats and inhibitsNa+ uptake in humans.
1253 Connop BP et al.Novel effects of FCCP [carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone] on amyloid precursor protein processing. J Neurochem. 1999 Apr;72(4):1457-65.
1254 Tanpradit N, et al. Carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) pre-exposure ensures follicle integrity during in vitro culture of ovarian tissue but not during cryopreservation in the domestic cat model. J Assist Reprod Genet. 2016 Dec;33(12):1621-1631. Epub 2016 Sep 17.
1255 Kondapalli C, et al. PINK1 is activated by mitochondrial membrane potential depolarization and stimulates Parkin E3 ligase activity by phosphorylating Serine 65. Open Biol. 2012 May;2(5):120080.
1256 Makoto Urai,et al. Potent Drugs That Attenuate anti-Candida Albicans Activity of Fluconazole and Their Possible Mechanisms of Action. J Infect Chemother. 2014 Oct;20(10):612-5.
1257 Wijtmans M, et al. Synthesis, modeling and functional activity of substituted styrene-amides as small-molecule CXCR7 agonists. Eur J Med Chem. 2012 May;51:184-92.
1258 Khan MS, et al. Design, synthesis, evaluation and thermodynamics of 1-substituted pyridylimidazo[1,5-a]pyridine derivatives as cysteine protease inhibitors. PLoS One. 2013 Aug 5;8(8):e69982.
1259 Toda G, et al. Calcium-activated neutral protease inhibitor (E-64c) and reperfusion for experimental myocardial infarction. Jpn Heart J. 1989 May;30(3):375-86.
1260 Radzey H, et al. E-64c-hydrazide: a lead structure for the development of irreversible cathepsin C inhibitors. ChemMedChem. 2013 Aug;8(8):1314-21.
1261 Ji Yeun Kim, et al. Safe, High-Throughput Screening of Natural Compounds of MERS-CoV Entry Inhibitors Using a Pseudovirus Expressing MERS-CoV Spike Protein. Int J Antimicrob Agents. 2018 Nov;52(5):730-732.
1262 https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=PREDNISOLONE+&cntry=&state=&city=&dist=&Search=Search
1263 Drugs Today (2003), 39(3), 157-74; Prog. Med. Chem. (1985), 21,111-135; Chemotherapy (1981), 27 Suppl 2, 107-20
1264 https://clinicaltrials.gov/ct2/show/NCT04900129?term=Sodium+Salicylate&cond=covid&draw=2&rank=1
1265 Nelson RM, et al.Electrophysiological actions of gamma-aminobutyric acid and clomethiazole on recombinant GABA(A) receptors.Eur J Pharmacol. 2002 Oct 11;452(3):255-62.
1266 Stresser DM, et al. Selective Time- and NADPH-Dependent Inhibition of Human CYP2E1 by Clomethiazole.Drug Metab Dispos. 2016 Aug;44(8):1424-30
1267 Monica M. Mita, et al. A phase Ia study of CC-90003, a selective extracellular signal-regulated kinase (ERK) inhibitor, in patients with relapsed or refractory BRAF or RAS-mutant tumors. Journal of Clinical Oncology 35, no. 15_suppl (May 20 2017) 2577-2577.
1268 Hideshima T, et al. NF-kappa B as a therapeutic target in multiple myeloma. J Biol Chem. 2002 May 10;277(19):16639-47.
1269 Vodanovic-Jankovic S, et al. NF-kappaB as a target for the prevention of graft-versus-host disease: comparative efficacy of bortezomib and PS-1145. Blood. 2006 Jan 15;107(2):827-34.
1270 Oh-I S, et al. Central administration of interleukin-4 exacerbates hypothalamic inflammation and weight gain during high-fat feeding. Am J Physiol Endocrinol Metab. 2010 Jul;299(1):E47-53.
1271 Antimicrob Agents Chemother 13:536 (1978); J Antimicrob Chemother 6:113 (1980); J Pharmacol Exp Therap 226:226 (1983)
1272 Hong SW, et al. SB365, Pulsatilla saponin D, targets c-Met and exerts antiangiogenic and antitumor activities. Carcinogenesis. 2013 Sep;34(9):2156-69.
1273 Son MK, et al. SB365, Pulsatilla saponin D suppresses proliferation and induces apoptosis of pancreatic cancer cells. Oncol Rep. 2013 Aug;30(2):801-8.
1274 Son MK, et al. SB365, Pulsatilla saponin D suppresses the proliferation of human colon cancer cells and induces apoptosis by modulating the AKT/mTOR signalling pathway. Food Chem. 2013 Jan 1;136(1):26-33.
1275 Yong Kim, et al. Pulsatilla saponin D: the antitumor principle from Pulsatilla koreana. Arch Pharm Res. 2004 Sep;27(9):915-8.
1276 Snowdy S, et al. A comparison of an A1 adenosine receptor agonist (CVT-510) with diltiazem for slowing of AVnodal conduction in guinea-pig. Br J Pharmacol. 1999 Jan;126(1):137-46.
1277 Fraser H, et al. N-[3-(R)-tetrahydrofuranyl]-6-aminopurine riboside, an A1 adenosine receptor agonist, antagonizes catecholamine-induced lipolysis without cardiovascular effects in awake rats. J Pharmacol Exp Ther. 2003 Apr;305(1):225-31.
1278 Nibret E, et al. Biological activities of xanthatin from Xanthium strumarium leaves.Phytother Res. 2011 Dec;25(12):1883-90.
1279 Yu Y, et al. Xanthatin, a novel potent inhibitor of VEGFR2 signaling, inhibits angiogenesis and tumor growth in breast cancer cells.Int J Clin Exp Pathol. 2015 Sep 1;8(9):10355-64.
1280 Khuchtumur Bum-Erdene, et al. Small-Molecule Covalent Modification of Conserved Cysteine Leads to Allosteric Inhibition of the TEAD⋅Yap Protein-Protein Interaction. Cell Chem Biol. 2019 Mar 21;26(3):378-389.e13.
1281 Ashford AL, et al. A novel DYRK1B inhibitor AZ191 demonstrates that DYRK1B acts independently of GSK3β to phosphorylate cyclin D1 at Thr(286), not Thr(288). Biochem J. 2014 Jan 1;457(1):43-56.
1282 Chen H, et al. Targeting DYRK1B suppresses the proliferation and migration of liposarcoma cells. Oncotarget. 2017 Nov 28;9(17):13154-13166.
1283 Zhonghua Yi Xue Za Zhi 55:31 (1995)
1284 Jean Herman, et al. Autoimmune and inflammatory disorder therapy. From PCT Int. Appl. (2013), WO 2013034738 A1
1285 Hooper AM, et al. Isoschaftoside, a C-glycosylflavonoid from Desmodium uncinatum root exudate, is an allelochemical against the development of Striga. Phytochemistry. 2010 Jun;71(8-9):904-8.
1286 Hamilton ML, et al. Elucidation of the biosynthesis of the di-C-glycosylflavone isoschaftoside, an allelopathic component from Desmodium spp. that inhibits Striga spp. development. Phytochemistry. 2012 Dec;84:169-76.
1287 Shu Shan Du, et al. Nematocidal flavone-C-glycosides against the root-knot nematode (Meloidogyne incognita) from Arisaema erubescens tubers. Molecules. 2011 Jun 20;16(6):5079-86.
1288 Ngan VK, et al. Mechanism of mitotic block and inhibition of cell proliferation by the semisynthetic Vinca alkaloids vinorelbine and its newer derivative vinflunine. Mol Pharmacol. 2001 Jul;60(1):225-32.
1289 Liu XM, et al. Unique induction of p21(WAF1/CIP1)expression by vinorelbine in androgen-independent prostate cancer cells. Br J Cancer. 2003 Oct 20;89(8):1566-73.
1290 Poirier VJ, et al. Toxicity, dosage, and efficacy of vinorelbine (Navelbine) in dogs with spontaneous neoplasia. J Vet Intern Med. 2004 Jul-Aug;18(4):536-9.
1291 Pierro JA, et al. Phase I clinical trial of vinorelbine in tumor-bearing cats. J Vet Intern Med. 2013 Jul-Aug;27(4):943-8.
1292 J Chem Soc 1959: 2679; 1963: 5573
1293 Wenteng Chen, et al. CN128: A New Orally Active Hydroxypyridinone Iron Chelator. J Med Chem. 2020 Apr 23;63(8):4215-4226.
1294 https://clinicaltrials.gov/ct2/show/NCT04505098?term=Eicosapentaenoic+Acid&cond=Covid19&draw=2&rank=7 https://trialsearch.who.int/Trial2.aspx?TrialID=EUCTR2020-001396-33-GB
1295 J Anim Sci 71:2439 (1993); 72:75 (1994)
1296 JACS 74:1868, 3455 (1992); Angewante Chemie Int Ed 4:846 (1965); Arzneim Forsch 20:1210 (1970)
1297 Langlois X, et al. Pharmacology of JNJ-37822681, a specific and fast-dissociating D2 antagonist for the treatment of schizophrenia. J Pharmacol Exp Ther. 2012 Jul;342(1):91-105.
1298 Ran X, et al. Farrerol Ameliorates TNBS-Induced Colonic Inflammation by Inhibiting ERK1/2, JNK1/2, and NF-κB Signaling Pathway. Int J Mol Sci. 2018 Jul 13;19(7).
1299 Cui B, et al. Farrerol attenuates β-amyloid-induced oxidative stress and inflammation through Nrf2/Keap1 pathway in a microglia cell line. Biomed Pharmacother. 2019 Jan;109:112-119.
1300 Dai F, et al. Farrerol inhibited angiogenesis through Akt/mTOR, Erk and Jak2/Stat3 signal pathway. Phytomedicine. 2016 Jun 15;23(7):686-93.
1301 Li B, et al. Farrerol overcomes the invasiveness of lung squamous cell carcinoma cells by regulating the expression of inducers of epithelial mesenchymal transition. Microb Pathog. 2019 Jun;131:277.
1302 Li Y, et al. Farrerol protects dopaminergic neurons in a rat model of lipopolysaccharide-induced Parkinson's disease by suppressing the activation of the AKT and NF-κB signaling pathways. Int Immunopharmacol. 2019 Oct;75:105739.
1303 Wang L, et al. Farrerol Ameliorates APAP-induced Hepatotoxicity via Activation of Nrf2 and Autophagy. Int J Biol Sci. 2019 Jan 29;15(4):788-799.
1304 JAMA 250:2469 (1983); J Environ Sci Health B28:413 (1993); Indian Vet J 74:565 (1997);
1305 Calamini B, et al. ML346: A Novel Modulator of Proteostasis for Protein Conformational Diseases.Probe Reports from the NIH Molecular Libraries Program. Bethesda (MD): National Center for Biotechnology Information (US); 2010-.&#x0D; 2012 Dec 17.
1306 Calamini B, et al. Small-molecule proteostasis regulators for protein conformational diseases. Nat Chem Biol. 2011 Dec 25;8(2):185-96.
1307 Sharif NA, et al. Emedastine: a potent, high affinity histamine H1-receptor-selective antagonist for ocular use: receptor binding and second messenger studies. J Ocul Pharmacol. 1994 Winter;10(4):653-64.
1308 Murota H, et al. Emedastine difumarate: a review of its potential ameliorating effect for tissue remodeling in allergic diseases. Expert Opin Pharmacother. 2009 Aug;10(11):1859-67.
1309 Andoh T, et al. Involvement of blockade of leukotriene B(4) action in anti-pruritic effects of emedastine in mice. Eur J Pharmacol. 2000 Oct 6;406(1):149-52.
1310 Allen JE, et al. Dual inactivation of Akt and ERK by TIC10 signals Foxo3a nuclear translocation, TRAIL gene induction, and potent antitumor effects. Sci Transl Med. 2013 Feb 6;5(171):171ra17.
1311 Jimenez JM, et al. Design and optimization of selective protein kinase C θ (PKCθ) inhibitors for the treatment of autoimmune diseases. J Med Chem. 2013 Mar 14;56(5):1799-810.
1312 Kunitomo J, et al. Discovery of 1-[2-Fluoro-4-(1H-pyrazol-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one (TAK-063), a Highly Potent, Selective, and Orally Active Phosphodiesterase 10A (PDE10A) Inhibitor. J Med Chem. 2014 Nov 26;57(22):9627-43.
1313 Suzuki K, et al. In Vivo Pharmacological Characterization of TAK-063, a Potent and Selective Phosphodiesterase 10A Inhibitor with Antipsychotic-Like Activity in Rodents. J Pharmacol Exp Ther. 2014 Dec 18. pii: jpet.114.218552.
1314 Liou CJ, et al. Ginkgolide C Suppresses Adipogenesis in 3T3-L1 Adipocytes via the AMPK Signaling Pathway. Evid Based Complement Alternat Med. 2015;2015:298635.
1315 Ginkgolide C, et al. Ginkgolide C inhibits platelet aggregation in cAMP- and cGMP-dependent manner by activating MMP-9. Biol Pharm Bull. 2007 Dec;30(12):2340-4.
1316 Wood KW, et al. Antitumor activity of an allosteric inhibitor of centromere-associated protein-E. Proc Natl Acad Sci U S A. 2010 Mar 30;107(13):5839-44.
1317 Mayes PA, et al. Mitogen-activated protein kinase (MEK/ERK) inhibition sensitizes cancer cells to centromere-associated protein E (CENP-E) inhibition. Int J Cancer. 2013 Feb 1;132(3):E149-57.
1318 Balamuth NJ, et al. Serial transcriptome analysis and cross-species integration identifies centromere-associated protein E as a novel neuroblastoma target. Cancer Res. 2010 Apr 1;70(7):2749-58.
1319 Nguyen D, et al. Discovery and Characterization of the Potent and Highly Selective (Piperidin-4-yl)pyrido[3,2- d]pyrimidine Based in Vitro Probe BAY-885 for the Kinase ERK5. J Med Chem. 2019 Jan 24;62(2):928-940.
1320 Hatanaka H, Kino T, Miyata S, FR-900520 and FR-900523, novel immunosuppressants isolated from a Streptomyces. II. Fermentation, isolation and physico-chemical and biological characteristics. J Antibiot (Tokyo). 1988 Nov;41(11):1592-601.
1321 Teutsch M, Higer M, Wang D, Induction of CD5 on B and T cells is suppressed by cyclosporin A, FK-520 and rapamycin. Int Immunol. 1995 Mar;7(3):381-92.
1322 Mollison KW, Fey TA, Krause RA, Nephrotoxicity studies of the immunosuppressants tacrolimus (FK506) and ascomycin in rat models. Toxicology. 1998 Feb 6;125(2-3):169-81.
1323 Appel NM, et al. Dopamine D3 Receptor Antagonist (GSK598809) Potentiates the Hypertensive Effects of Cocaine in Conscious, Freely-Moving Dogs. J Pharmacol Exp Ther. 2015 Sep;354(3):484-92.
1324 Micheli F, et al. 1,2,4-Triazolyl azabicyclo[3.1.0]hexanes: a new series of potent and selective dopamine D(3) receptor antagonists. J Med Chem. 2010 Jan 14;53(1):374-91.
1325 Watahiki H, Yagishita S, Futai E, Ishiura S.CTF1-51, a truncated carboxyl-terminal fragment of amyloid precursor protein, suppresses the effects of Aβ42-lowering γ-secretase modulators.Neurosci Lett. 2012 Sep 27;526(2):96-9. Epub 2012 Aug 23.
1326 Wanngren J, Ottervald J, Parpal S, Portelius E, Str?mberg K, Borgeg?rd T, Klintenberg R, Juréus A, Blomqvist J, Blennow K, Zetterberg H, Lundkvist J, Rosqvist S, Karlstr?m H.Second generation γ-secretase modulators exhibit different modulation of Notch β and Aβ production.J Biol Chem. 2012 Jul 31.
1327 Wagner SL, Tanzi RE, Mobley WC, Galasko D.Potential Use of γ-Secretase Modulators in the Treatment of Alzheimer Disease.Arch Neurol. 2012 Jul 16:1-4.
1328 Bulic B, Ness J, Hahn S, Rennhack A, Jumpertz T, Weggen S.Chemical Biology, Molecular Mechanism and Clinical Perspective of γ-Secretase Modulators in Alzheimer's Disease.Curr Neuropharmacol. 2011 Dec;9(4):598-622.
1329 Kretner, Benedikt; Fukumori, Akio; Gutsmiedl, Amelie; Page, Richard M.; Luebbers, Thomas; Galley, Guido; Baumann, Karlheinz; Haass, Christian; Steiner, Harald. Attenuated A.beta.42 Responses to Low Potency .gamma.-Secretase Modulators Can Be Overcome for Many Pathogenic Presenilin Mutants by Second-generation Compounds. Journal of Biological Chemistry (2011), 286(17), 15240-15251.
1330 Swale DR, et al. An insecticide resistance-breaking mosquitocide targeting inward rectifier potassium channels in vectors of Zika virus and malaria. Sci Rep. 2016 Nov 16;6:36954.
1331 Nahoum V, et al. Modulators of the structural dynamics of the retinoid X receptor to reveal receptor function. Proc Natl Acad Sci U S A. 2007 Oct 30;104(44):17323-8.
1332 Bai A, et al. Targeting (cellular) lysosomal acid ceramidase by B13: design, synthesis and evaluation of novel DMG-B13 ester prodrugs. Bioorg Med Chem. 2014 Dec 15;22(24):6933-44.
1333 Cameron KO, et al. Discovery and Preclinical Characterization of 6-Chloro-5-[4-(1-hydroxycyclobutyl)phenyl]-1H-indole-3-carboxylic Acid (PF-06409577), a Direct Activator of Adenosine Monophosphate-activated Protein Kinase (AMPK), for the Potential Treatment of Diabetic Nephropathy. J Med Chem. 2016 Sep 8;59(17):8068-81.
1334 Salatto CT, et al. Selective Activation of AMPK β1-Containing Isoforms Improves Kidney Function in a Rat Model of Diabetic Nephropathy. J Pharmacol Exp Ther. 2017 May;361(2):303-311.
1335 Hansen KB, et al. Structural and mechanistic determinants of a novel site for noncompetitive inhibition of GluN2D-containing NMDA receptors. J Neurosci. 2011 Mar 9;31(10):3650-3661.
1336 Aneesh Sivaraman, et al. Synthesis and Structure-Activity Relationships of Arylsulfonamides as AIMP2-DX2 Inhibitors for the Development of a Novel Anticancer Therapy. J Med Chem. 2020 May 28;63(10):5139-5158.
1337 J Chem Soc 1939:956; Biochem Syst Ecol 20:481 (1992)
1338 Ann Rev Biochem 20:441 (1951); Clin Pharmacol Ther 59:613 (1996)
1339 Robert Peery,et al. Synthesis and Identification of a Novel Lead Targeting Survivin Dimerization for Proteasome-Dependent Degradation. J Med Chem. 2020 Jun 9.
1340 Morinaga, A., et al., Effects of sex hormones on Alzheimer's disease-associated beta-amyloid oligomer formation in vitro. Exp Neurol, 2011. 228(2): p. 298-302.
1341 Begum, M., et al., Neonatal estrogenic exposure suppresses PTEN-related endometrial carcinogenesis in recombinant mice. Lab Invest, 2006. 86(3): p. 286-96.
1342 Hewitt, S.C. and K.S. Korach, Estrogenic activity of bisphenol A and 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE) demonstrated in mouse uterine gene profiles. Environ Health Perspect, 2011. 119(1): p. 63-70. |JACS 76:2943 (1954); Biochem Prep 12:81 (1968); J Steroid Biochem 20:945 (1984)
1343 Liu G, et al. Discovery of AC710, a Globally Selective Inhibitor of Platelet-Derived Growth Factor Receptor-Family Kinases. ACS Med Chem Lett. 2012 Sep 24;3(12):997-1002.
1344 Price GW, et, al. SB-216641 and BRL-15572--compounds to pharmacologically discriminate h5-HT1B and h5-HT1D receptors. Naunyn Schmiedebergs Arch Pharmacol. 1997 Sep; 356(3): 312-20.
1345 Geovanna NQ, et, al. Antinociceptive effect of (-)-epicatechin in inflammatory and neuropathic pain in rats. Behav Pharmacol. 2018 Apr; 29(2 and 3-Spec Issue): 270-279.
1346 Hagan JJ, et, al. Stimulation of 5-HT1B receptors causes hypothermia in the guinea pig. Eur J Pharmacol. 1997 Jul 23; 331(2-3): 169-74.
1347 Nitsch E, et al. Synergistic cytotoxic activity of treosulfan and LY 188011 in pancreatic cancer cell lines. Anticancer Res. 2014 Apr;34(4):1779-84.
1348 Peter T, et al. Programmed erythrocyte death following in vitro Treosulfan treatment. Cell Physiol Biochem. 2015;35(4):1372-80.
1349 Sjöö F, et al. Myeloablative and immunosuppressive properties of treosulfan in mice. Exp Hematol. 2006 Jan;34(1):115-21.
1350 Rudolf K, et al. Development of human calcitonin gene-related peptide (CGRP) receptor antagonists. 1. Potent and selective small molecule CGRP antagonists. 1-[N2-[3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-l-lysyl]-4-(4-pyridinyl)piperazine: the first CGRP antagonist for clinical trials in acute migraine. J Med Chem. 2005 Sep 22;48(19):5921-31.
1351 Doods H, et al. Pharmacological profile of BIBN4096BS, the first selective small molecule CGRP antagonist. Br J Pharmacol. 2000 Feb;129(3):420-3.
1352 Edvinsson L, et al. Effect of the CGRP receptor antagonist BIBN4096BS in human cerebral, coronary and omentalarteries and in SK-N-MC cells. Eur J Pharmacol. 2002 Jan 2;434(1-2):49-53.
1353 Sixt ML, et al. Calcitonin gene-related peptide receptor antagonist Olcegepant acts in the spinal trigeminal nucleus. Brain. 2009 Nov;132(Pt 11):3134-41.
1354 Michot B, et al. Differential effects of calcitonin gene-related peptide receptor blockade by Olcegepant on mechanical allodynia induced by ligation of the infraorbital nerve vs the sciatic nerve in the rat. Pain. 2012 Sep;153(9):1939-48.
1355 Ann 180:71 (1876); 230:225 (1885); J Chem Soc 127:1632 (1925)
1356 Bravo Y, et al. Identification of the first potent, selective and bioavailable PPARα antagonist. Bioorg Med Chem Lett. 2014 May 15;24(10):2267-72.
1357 Nissen SE, et al. Effects of a potent and selective PPAR-alpha agonist in patients with atherogenic dyslipidemia or hypercholesterolemia: two randomized controlled trials. JAMA. 2007 Mar 28;297(12):1362-73.
1358 Khera AV, et al. Potent peroxisome proliferator-activated receptor-α agonist treatment increases cholesterol efflux capacity in humans with the metabolic syndrome. Eur Heart J. 2015 Nov 14;36(43):3020-2.
1359 Vertosick FT Jr, et al. A comparison of the relative chemosensitivity of human gliomas to tamoxifen and n-desmethyltamoxifen in vitro. J Neurooncol. 1994;19(2):97-103.
1360 Morad SA, et al. Modification of sphingolipid metabolism by tamoxifen and N-desmethyltamoxifen in acute myelogenous leukemia--Impact on enzyme activity and response to cytotoxics. Biochim Biophys Acta. 2015 Jul;1851(7):919-28.
1361 Reddel RR,et al. N-desmethyltamoxifen inhibits growth of MCF 7 human mammary carcinoma cells in vitro. Eur J Cancer Clin Oncol. 1983 Aug;19(8):1179-81.
1362 Yin Z, et al. Increased MMPs expression and decreased contraction in the rat myometrium during pregnancy and in response to prolonged stretch and sex hormones. Am J Physiol Endocrinol Metab. 2012 Jul 1;303(1):E55-70.
1363 Botos I, et al. Batimastat, a potent matrix mealloproteinase inhibitor, exhibits an unexpected mode of binding. Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2749-54.
1364 Hansen HP, et al. Inhibition of metalloproteinases enhances the internalization of anti-CD30 antibody Ki-3 and the cytotoxic activity of Ki-3 immunotoxin. Int J Cancer. 2002 Mar 10;98(2):210-5.
1365 Giavazzi R, et al. Batimastat, a synthetic inhibitor of matrix metalloproteinases, potentiates the antitumor activity of cisplatin in ovarian carcinoma xenografts. Clin Cancer Res. 1998 Apr;4(4):985-92.
1366 Ricci S, et al. Inhibition of matrix metalloproteinases attenuates brain damage in experimental meningococcal meningitis. BMC Infect Dis. 2014 Dec 31;14:726.
1367 Russo LA, et al. Regulated expression of matrix metalloproteinases, inflammatory mediators, and endometrial matrix remodeling by 17beta-estradiol in the immature rat uterus. Reprod Biol Endocrinol. 2009 Nov 4;7:124.
1368 J Am Vet Med Assoc 202:273 (1993)
1369 Park HJ, et al. 1-O-Hexyl-2,3,5-Trimethylhydroquinone Ameliorates l-DOPA-Induced Cytotoxicity in PC12 Cells. Molecules. 2019 Mar 1;24(5). pii: E867.
1370 Jung YR et al. Inhibitory Effect of 1-O-Hexyl-2,3,5-Trimethylhydroquinone on Dimethylnitrosamine-induced Liver Fibrosis in Male SD Rats. Toxicol Res. 2010 Sep;26(3):193-201.
1371 Hermes-Lima M, et al. The iron chelator pyridoxal isonicotinoyl hydrazone (PIH) and its analogues prevent damage to 2-deoxyribose mediated by ferric iron plus ascorbate. Biochim Biophys Acta. 2000 Oct 18;1523(2-3):154-60.
1372 Landschulz W, et al. A lipophilic iron chelator can replace transferrin as a stimulator of cell proliferation and differentiation. J Cell Biol. 1984 Feb;98(2):596-601.
1373 Chatterjee A, et al. Safety, tolerability, and pharmacokinetics of a capsule formulation of DRF-1042, a novelcamptothecin analog, in refractory cancer patients in a bridging phase I study. J Clin Pharmacol. 2005 Apr;45(4):453-60.
1374 Sriram Rajagopal, et al. Preclinical evaluation of the anticancer activity of DRF-1042, a novel camptothecin analog targeting Topoisomerase-I. Published April 2004.
1375 Yie Y, et al. Ursolic acid inhibited growth of hepatocellular carcinoma HepG2 cells through AMPKα-mediated reduction of DNA methyltransferase 1. Mol Cell Biochem. 2014 Dec 30.
1376 Kim M, et al. The combination of ursolic acid and leucine potentiates the differentiation of C2C12 murine myoblasts through the mTOR signaling pathway. Int J Mol Med. 2015 Mar;35(3):755-62.
1377 Kim ES, et al. Ursolic acid inhibits the invasive phenotype of SNU-484 human gastric cancer cells. Oncol Lett. 2015 Feb;9(2):897-902.
1378 Li R, et al. Ursolic Acid Promotes Apoptosis of SGC-7901 Gastric Cancer Cells through ROCK/PTEN Mediated Mitochondrial Translocation of Cofilin-1. Asian Pac J Cancer Prev. 2014;15(22):9593-7.
1379 Hu Z, et al. Ursolic acid improves survival and attenuates lung injury in septic rats induced by cecal ligation and puncture. J Surg Res. 2014 Oct 22. pii: S0022-4804(14)00967-6. |Phytochemistry 10:3279 (1971); Cancer Lett 33:279 (1986)
1380 Purkey HE, et al. Cell Active Hydroxylactam Inhibitors of Human Lactate Dehydrogenase with Oral Bioavailability in Mice. ACS Med Chem Lett. 2016 Aug 26;7(10):896-901.
1381 Biochem Pharmacol 50:1943 (1995); Cancer Chemother Pharmacol 40:376 (1997)
1382 Eur J Pharmacol 59:1 (1979); Arzneim Forsch 31:849 (1981); Drugs 35 Suppl 6:147 (1988)
1383 Murayama N, et al. SUN11602, a novel aniline compound, mimics the neuroprotective mechanisms of basic fibroblast growth factor. ACS Chem Neurosci. 2013 Feb 20;4(2):266-76.
1384 Murayama N, et al. SUN11602-induced hyperexpression of calbindin D-28k is pivotal for the survival of hippocampal neurons under neurotoxic conditions. Brain Res. 2015 Jan 12;1594:71-81.
1385 Ogino R, et al. SUN11602 has basic fibroblast growth factor-like activity and attenuates neuronal damage and cognitive deficits in a rat model of Alzheimer's disease induced by amyloid β and excitatory amino acids. Brain Res. 2014 Oct 17;1585:159-66.
1386 Sutherlin DP, et al. Discovery of (thienopyrimidin-2-yl)aminopyrimidines as potent, selective, and orally available pan-PI3-kinase and dual pan-PI3-kinase/mTOR inhibitors for the treatment of cancer. J Med Chem. 2010 Feb 11;53(3):1086-97.
1387 Nair MS, et al. Bioconversion of arteannuin B to artemisinin. J Nat Prod. 1993 Sep;56(9):1559-66.
1388 Ruiyuan Cao, et al. Anti-SARS-CoV-2 Potential of Artemisinins In Vitro. RETURN TO JUST ACCEPTED MANUSCRIPTS.
1389 Moriconi A, et al. Design of noncompetitive interleukin-8 inhibitors acting on CXCR1 and CXCR2. J Med Chem. 2007 Aug 23;50(17):3984-4002.
1390 Bertini R, et al. Receptor binding mode and pharmacological characterization of a potent and selective dual CXCR1/CXCR2non-competitive allosteric inhibitor. Br J Pharmacol. 2012 Jan;165(2):436-54.
1391 Kim HY, et al. Reparixin, an inhibitor of CXCR1 and CXCR2 receptor activation, attenuates blood pressure and hypertension-related mediators expression in spontaneously hypertensive rats. Biol Pharm Bull. 2011;34(1):120-7.
1392 Sousa LF, et al. Blockade of CXCR1/2 chemokine receptors protects against brain damage in ischemic stroke in mice. Clinics (Sao Paulo). 2013;68(3):391-4.
1393 Bertini R, et al. Noncompetitive allosteric inhibitors of the inflammatory chemokine receptors CXCR1 and CXCR2: prevention of reperfusion injury. Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11791-6.
1394 Krishnamurthy A, et al. Identification of a novel chemokine-dependent molecular mechanism underlying rheumatoid arthritis-associated autoantibody-mediated bone loss. Ann Rheum Dis. 2016 Apr;75(4):721-9.
1395 Crespo J, et al. Human Naive T Cells Express Functional CXCL8 and Promote Tumorigenesis. J Immunol. 2018 Jul 15;201(2):814-820.
1396 Villarino N, et al. Pharmacokinetics of tulathromycin in healthy and neutropenic mice challenged intranasally with lipopolysaccharide from Escherichia coli. Antimicrob Agents Chemother. 2012;56(8):4078-4086.
1397 Andersen NM, et al. Inhibition of protein synthesis on the ribosome by tildipirosin compared with other veterinary macrolides. Antimicrob Agents Chemother. 2012;56(11):6033-6036.
1398 Duquette SC, et al. Immunomodulatory effects of tulathromycin on apoptosis, efferocytosis, and proinflammatory leukotriene B4 production in leukocytes from Actinobacillus pleuropneumoniae-or zymosan-challenged pigs. Am J Vet Res. 2015;76(6):507-519.
1399 Curr Neurol Neurosci Reports 4:155 (2004); Sleep Med 10:661 (2009); J Clin Sleep Med 5:365 (2009)
1400 Terayama H, et al. Effect of acetamiprid on the immature murine testes. Int J Environ Health Res. 2018 Dec;28(6):683-696.
1401 Kong D, et al. Acetamiprid inhibits testosterone synthesis by affecting the mitochondrial function and cytoplasmic adenosine triphosphate production in rat Leydig cells. Biol Reprod. 2017 Jan 1;96(1):254-265.
1402 Drug Intell Clin Pharm 11:110 (1977); Clin Pediatr 16:901 (1977); Clin Toxicol 44:357 (2006)|
1403 Chen W, et al. Camphor--a fumigant during the Black Death and a coveted fragrant wood in ancient Egypt and Babylon--a review. Molecules. 2013 May 10;18(5):5434-54.
1404 Billen B, et al. Different ligands of the TRPV3 cation channel cause distinct conformational changes as revealedby intrinsic tryptophan fluorescence quenching. J Biol Chem. 2015 May 15;290(20):12964-74.
1405 Tran TA, et al. Camphor Induces Proliferative and Anti-senescence Activities in Human Primary Dermal Fibroblasts and Inhibits UV-Induced Wrinkle Formation in Mouse Skin. Phytother Res. 2015 Dec;29(12):1917-25.
1406 Crocker CE, et al. JNK Inhibition Protects Dopamine Neurons and Provides Behavioral Improvement in a Rat 6-hydroxydopamine Model of Parkinson's Disease. ACS Chem Neurosci. 2011 Apr 20;2(4):207-212.
1407 Chambers JW, et al. Inhibition of JNK mitochondrial localization and signaling is protective against ischemia/reperfusion injury in rats. J Biol Chem. 2013 Feb 8;288(6):4000-11.
1408 Gao S, et al. Pharmacological Inhibition of c-Jun N-terminal Kinase Reduces Food Intake and Sensitizes Leptin's Anorectic Signaling Actions. Sci Rep. 2017 Feb 6;7:41795.
1409 Glover V, et al. Isatin: Identity with the Purified Endogenous Monoamine Oxidase Inhibitor Tribulin. Journal of Neurochemistry, 51(2), 656–659.
1410 Igosheva N, et al. Isatin, an endogenous monoamine oxidase inhibitor, triggers a dose- and time-dependent switch from apoptosis to necrosis in human neuroblastoma cells. Neurochem Int. 2005 Aug;47(3):216-24.
1411 McIntyre IM, et al. Serotonergic effects of isatin: an endogenous MAO inhibitor related to tribulin. J Neural Transm Gen Sect. 1990;79(1-2):35-40.
1412 Benned-Jensen T, et al. Ligand modulation of the Epstein-Barr virus-induced seven-transmembrane receptor EBI2: identification of a potent and efficacious inverse agonist. J Biol Chem. 2011 Aug 19;286(33):29292-302.
1413 Shimada K, et al. Global survey of cell death mechanisms reveals metabolic regulation of ferroptosis. Nat Chem Biol. 2016 Jul;12(7):497-503.
1414 Dixon SJ, et al. Human Haploid Cell Genetics Reveals Roles for Lipid Metabolism Genes in Nonapoptotic Cell Death. ACS Chem Biol. 2015 Jul 17;10(7):1604-9.
1415 Burslem GM, et al. Targeting BCR-ABL1 in Chronic Myeloid Leukemia by PROTAC-mediated Targeted Protein Degradation. Cancer Res. 2019 Jul 16. pii: canres.1236.2019.
1416 Mahameed M,et al. The unfolded protein response modulators GSK2606414 and KIRA6 are potent KIT inhibitors. Cell Death Dis. 2019 Apr 1;10(4):300.
1417 Ghosh R, et al. Allosteric inhibition of the IRE1α RNase preserves cell viability and function during endoplasmic reticulum stress. Cell. 2014 Jul 31;158(3):534-48.
1418 Yallappa Rajashekar, et al. Acetylcholinesterase Inhibition by Biofumigant (Coumaran) From Leaves of Lantana Camara in Stored Grain and Household Insect Pests. Biomed Res Int. 2014;2014:187019.
1419 Paganelli FL, et al. Lipoteichoic acid synthesis inhibition in combination with antibiotics abrogates growth of multidrug-resistant Enterococcus faecium.Int J Antimicrob Agents. 2017 Mar;49(3):355-363.
1420 Lundgren, Karen., et al. BIIB021, an orally available, fully synthetic small-molecule inhibitor of the heat shock protein Hsp90. Molecular Cancer Therapeutics (2009), 8(4), 921-929.
1421 B?ll B, et al. Heat shock protein 90 inhibitor BIIB021 (CNF2024) depletes NF-kappaB and sensitizes Hodgkin's lymphoma cells for natural killer cell-mediated cytotoxicity. Clin Cancer Res. 2009 Aug 15;15(16):5108-16.
1422 Yin X, et al. BIIB021, a novel Hsp90 inhibitor, sensitizes head and neck squamous cell carcinoma to radiotherapy. Int J Cancer. 2010 Mar 1;126(5):1216-25
1423 Zhang H, et al. BIIB021, a synthetic Hsp90 inhibitor, has broad application against tumors with acquired multidrug resistance. Int J Cancer. 2010 Mar 1;126(5):1226-34
1424 Matsumoto K, et al. Suppressive effects of isorhynchophylline on 5-HT2A receptor function in the brain: behavioural and electrophysiological studies. Eur J Pharmacol. 2005 Jul 11;517(3):191-9.
1425 Cocco E, et al. KAT3B-p300 and H3AcK18/H3AcK14 levels are prognostic markers for kidney ccRCC tumoraggressiveness and target of KAT inhibitor CPTH2. Clin Epigenetics. 2018 Apr 4;10:44.
1426 Chimenti F, et al. A novel histone acetyltransferase inhibitor modulating Gcn5 network: cyclopentylidene-[4-(4'-chlorophenyl)thiazol-2-yl)hydrazone. J Med Chem. 2009 Jan 22;52(2):530-6.
1427 Jacqueline Sayyah, Andrew Magis, David A. Ostrov, et al. Z3, a novel Jak2 tyrosine kinase small-molecule inhibitor that suppresses Jak2-mediated pathologic cell growth . Mol Cancer Ther 2008;7(8):2308-18.
1428 Jacqueline Sayyah, Peter P. Sayeski. Jak2 inhibitors: Rationale and role as therapeutic agents in hematologic malignancies. Current Oncology Reports. 2009, 11(2): 117-124.
1429 Ehab Atallah , Srdan Verstovsek . Prospect of JAK2 inhibitor therapy in myeloproliferative neoplasms. Expert Review of Anticancer Therapy. 2009,9 (5):663-670.
1430 Boll Chim Farm106:8 (1967); Anal Profiles Drug Subs 12:385 (1983)
1431 Silva KA, et al. Inhibition of Stat3 activation suppresses caspase-3 and the ubiquitin-proteasome system, leading to preservation of muscle mass in cancer cachexia. J Biol Chem. 2015 Apr 24;290(17):11177-87.
1432 Redell MS, et al. Stat3 signaling in acute myeloid leukemia: ligand-dependent and -independent activation and induction of apoptosis by a novel small-molecule Stat3 inhibitor. Blood. 2011 May 26;117(21):5701-9.
1433 Bharadwaj U, et al. Small-molecule inhibition of STAT3 in radioresistant head and neck squamous cell carcinoma. Oncotarget. 2016 May 3;7(18):26307-30.
1434 Zhang H, et al. Targeting CDK9 Reactivates Epigenetically Silenced Genes in Cancer. Cell. 2018 Nov 15;175(5):1244-1258.e26.
1435 Liao F, et al. LSKL peptide alleviates subarachnoid fibrosis and hydrocephalus by inhibiting TSP1-mediated TGF-β1 signaling activity following subarachnoid hemorrhage in rats. Exp Ther Med. 2016 Oct;12(4):2537-2543. Epub 2016 Aug 31.
1436 Laurent MA, et al. In silico characterization of the interaction between LSKL peptide, a LAP-TGF-beta derived peptide, and ADAMTS1. Comput Biol Chem. 2016 Apr;61:155-61.
1437 Kuroki H, et al. Effect of LSKL peptide on thrombospondin 1-mediated transforming growth factor β signal activation and liver regeneration after hepatectomy in an experimental model. Br J Surg. 2015 Jun;102(7):813-25.
1438 Tuchman M, et al. Effects of uridine and thymidine on the degradation of 5-fluorouracil, uracil, and thymine by rat liver dihydropyrimidine dehydrogenase. Cancer Res. 1985 Nov;45(11 Pt 1):5553-6.
1439 Sensi M, et al. Human cutaneous melanomas lacking MITF and melanocyte differentiation antigens express a functional Axl receptor kinase. J Invest Dermatol. 2011 Dec;131(12):2448-57.
1440 Holland SJ, et al. R428, a selective small molecule inhibitor of Axl kinase, blocks tumor spread and prolongs survival in models of metastatic breast cancer. Cancer Res. 2010 Feb 15;70(4):1544-54.
1441 Lijnen HR, et al. Growth arrest-specific protein 6 receptor antagonism impairs adipocyte differentiation and adipose tissue development in mice. J Pharmacol Exp Ther. 2011 May;337(2):457-64.
1442 https://clinicaltrials.gov/ct2/show/NCT04816682?term=Silibinin&cond=covid-19&draw=2&rank=1
1443 El-Halfawy OM, et al. Discovery of an antivirulence compound that reverses β-lactam resistance in MRSA. Nat Chem Biol. 2019 Nov 25.
1444 Chen M, et al. Effects of beta-adrenoceptor antagonists on Ca(2+)-overload induced by lysophosphatidylcholine in rat isolated cardiomyocytes. Br J Pharmacol. 1996 Jun;118(4):865-70.
1445 Hashizume H, et al. Effects of antiischemic drugs on veratridine-induced hypercontracture in rat cardiac myocytes. Eur J Pharmacol. 1994 Dec 12;271(1):1-8.
1446 Acta Med Scand 127:471 (1947); Renal Physiol 237:F291 (1979); J Pharmacol Exp Therap 283:1018 (1997)
1447 Jerry Leroy Adams, et al. 5-sulfamoyl-2-hydroxybenzamide derivatives. WO 2017153952 A1.
1448 Mamun-Ur Rashid, et al. In vitro activity of MCB3681 against Clostridium difficile strains. Anaerobe 28 (2014) 216-219.
1449 Mitani Y, et al. Differential effects between γ-secretase inhibitors and modulators on cognitive function in amyloid precursor protein-transgenic and nontransgenic mice. J Neurosci. 2012 Feb 8;32(6):2037-50.
1450 Elvang AB, et al. Differential effects of gamma-secretase and BACE1 inhibition on brain Abeta levels in vitro and in vivo. J Neurochem. 2009 Sep;110(5):1377-87.
1451 Justice NJ, et al. Posttraumatic stress disorder-like induction elevates β-amyloid levels, which directly activates corticotropin-releasing factor neurons to exacerbate stress responses. J Neurosci. 2015 Feb 11;35(6):2612-23.
1452 Portelius E, et al. Acute effect on the Aβ isoform pattern in CSF in response to γ-secretase modulator and inhibitor treatment in dogs. J Alzheimers Dis. 2010;21(3):1005-12.
1453 Zhang L, et al. Mechanism of 2,3-butanediol stereoisomers formation in a newly isolated Serratia sp. T241. Sci Rep. 2016 Jan 12;6:19257.
1454 Clausen DM, et al. In vitro cytotoxicity and in vivo efficacy, pharmacokinetics, and metabolism of 10074-G5, a novel small-molecule inhibitor of c-Myc/Max dimerization. J Pharmacol Exp Ther. 2010 Dec;335(3):715-27.
1455 Chauhan J, et al. Discovery of methyl 4'-methyl-5-(7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)-[1,1'-biphenyl]-3-carboxylate, an improved small-molecule inhibitor of c-Myc-max dimerization. ChemMedChem. 2014 Oct;9(10):2274-85.
1456 Yap JL, et al. Pharmacophore identification of c-Myc inhibitor 10074-G5. Bioorg Med Chem Lett. 2013 Jan 1;23(1):370-4.
1457 J Biol Chem 192:569 (1951); Proc Natl Acad Sci 66:500 (1970); J Neurobiol 2:153 (1971)
1458 Bradwejn J, et al. Effects of PK 8165, a partial benzodiazepine receptor agonist, on cholecystokinin-inducedactivation of hippocampal pyramidal neurons: a microiontophoretic study in the rat. Eur J Pharmacol. 1985 Jun 19;112(3):415-8.
1459 Debonnel G, et al. Pipequaline acts as a partial agonist of benzodiazepine receptors: an electrophysiological study in the hippocampus of the rat. Neuropharmacology. 1987 Sep;26(9):1337-42.
1460 Toxicol Appl Pharmacol 18:185 (1971); Anal Profiles Drug Subs 12:357 (1983)
1461 Am. J. Cardiol. (1965), 16(6), 841-6; Arzneim. Forsch. (1962), 12, 902-7; J. Am. Med. Assoc. (1959), 169(15), 1742-7
1462 Arch Derm Syphilol 58:56 (1948); 67:479 (1953)
1463 http://www.ncbi.nlm.nih.gov/pubmed/10821781
1464 Roberts C, et al. The effect of SB-269970, a 5-HT(7) receptor antagonist, on 5-HT release from serotonergic terminals and cell bodies. Br J Pharmacol. 2001 Apr;132(7):1574-80.
1465 Monti JM, et al. The serotonin 5-HT7 receptor agonist LP-44 microinjected into the dorsal raphe nucleus suppresses REM sleep in the rat. Behav Brain Res. 2008 Aug 22;191(2):184-9.
1466 Nat. Rev. Neurol. (2010), 6(8), 420-421; CNS Drug Rev. (2007), 13(2), 224-239; Epilepsia (1964), 583-9
1467 Hatzelmann A, et al. The preclinical pharmacology of roflumilast--a selective, oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease. Pulm Pharmacol Ther. 2010 Aug;23(4):235-56.
1468 Rabe KF. Update on roflumilast, a phosphodiesterase 4 inhibitor for the treatment of chronic obstructive pulmonary disease. Br J Pharmacol. 2011 May;163(1):53-67.
1469 Hatzelmann A, et al. Anti-inflammatory and immunomodulatory potential of the novel PDE4 inhibitor roflumilast in vitro. J Pharmacol Exp Ther. 2001 Apr;297(1):267-79.
1470 Richmond BW, et al. Airway bacteria drive a progressive COPD-like phenotype in mice with polymeric immunoglobulin receptor deficiency. Nat Commun. 2016 Apr 5;7:11240.
1471 Ding H, et al. Treatment of obesity-associated overactive bladder by the phosphodiesterase type-4 inhibitor roflumilast. Int Urol Nephrol. 2017 Jul 29.
1472 Verstovsek S, et al. WP1066, a novel JAK2 inhibitor, suppresses proliferation and induces apoptosis in erythroid human cells carrying the JAK2 V617F mutation. Clin Cancer Res, 2008, (3), 788-796.
1473 Hatiboglu MA, et al. The tumor microenvironment expression of p-STAT3 influences the efficacy of WP1066 in murine melanoma models. Int J Cancer, 2012, 131(1), 8-17
1474 Ferrajoli A, et al. WP1066 disrupts Janus kinase-2 and induces caspase-dependent apoptosis in acute myelogenous leukemia cells. Cancer Res, 2007, 67(23), 11291-11299.
1475 Daigle SR, et al. Potent inhibition of DOT1L as treatment for MLL-fusion leukemia. Blood. 2013 Jun 25. [Epub ahead of print]
1476 Klaus CR, et al. DOT1L inhibitor EPZ-5676 displays synergistic antiproliferative activity in combination with standard of care drugs and hypomethylating agents in MLL-rearranged leukemia cells. J Pharmacol Exp Ther. 2014 Sep;350(3):646-56.
1477 Smith GF, et al. Identification of quinazoline based inhibitors of IRAK4 for the treatment of inflammation. Bioorg Med Chem Lett. 2017 Jun 15;27(12):2721-2726.
1478 Chen BK, et al. Prophylactic efficacy of 5-HT4R agonists against stress. Neuropsychopharmacology. 2019 Oct 10.
1479 Grimwood S, et al. Translational receptor occupancy for the 5-HT4 partial agonist PF-04995274 in rats, non-human primates and healthy volunteers. Alzheimer’s Dement: J Alzheimer’s Assoc. 2011;7:S653.
1480 Timothy Nicholas1, et al. Systems pharmacology modeling in neuroscience: Prediction and outcome of PF-04995274, a 5-HT4 partial agonist, in a clinical scopolamine impairment trial. Advances in Alzheimer's Disease. Vol.2 No.3(2013).
1481 Martin LJ, et al. Olesoxime, a cholesterol-like neuroprotectant for the potential treatment of amyotrophic lateral sclerosis. IDrugs. 2010 Aug;13(8):568-80.
1482 Bordet T, et al. Olesoxime (TRO19622): A Novel Mitochondrial-Targeted Neuroprotective Compound. Pharmaceuticals (Basel). 2010 Jan 28;3(2):345-368
1483 Bordet T, et al. Identification and characterization of cholest-4-en-3-one, oxime (TRO19622), a novel drug candidate for amyotrophic lateral sclerosis. J Pharmacol Exp Ther. 2007 Aug;322(2):709-20.
1484 Xiao WH, et al. Olesoxime (cholest-4-en-3-one, oxime): analgesic and neuroprotective effects in a rat model of painful peripheral neuropathy produced by the chemotherapeutic agent, paclitaxel. Pain. 2009 Dec 15;147(1-3):202-9
1485 Sato H, et al. Novel potent and selective bile acid derivatives as TGR5 agonists: biological screening, structure-activity relationships, and molecular modeling studies. J Med Chem. 2008 Mar 27;51(6):1831-41.
1486 Shih DM, et al. Hyodeoxycholic acid improves HDL function and inhibits atherosclerotic lesion formation in LDLR-knockout mice. FASEB J. 2013 Sep;27(9):3805-17.
1487 Sumaya IC, et al. Differential effects of a short-term high-fat diet in an animal model of depression in rats treated with the 5-HT3 receptor antagonist, ondansetron, the 5-HT3 receptor agonist, 2-methyl-5-HT, and the SSRI, fluoxetine. Pharmacol Biochem Behav. 2016 May;144:78-84.
1488 J Org Chem 16:1283 (1951); Acta Psychiatrica Scandinavica 81:162 (1990); J Pharmacy Pharmacol 47 :876 (1995)
1489 Qu XJ, et al. Induction of apoptosis in human hepatocellular carcinoma cells by synthetic antineoplaston A10. Anticancer Res. 2007 Jul-Aug;27(4B):2427-31.
1490 Nat. Prod. Comm. (2010), 5(12), 1999-2006; Curr. Bioact. Compd. (2006), 2(1), 57-66; Oral Surg., Oral Med., Oral Pathol. (1992), 73(6), 729-37
1491 Gever JR, et al. AF-353, a novel, potent and orally bioavailable P2X3/P2X2/3 receptor antagonist. Br J Pharmacol. 2010 Jul;160(6):1387-1398.
1492 Munoz A, et al. Modulation of bladder afferent signals in normal and spinal cord-injured rats by purinergic P2X3 and P2X2/3receptors. BJU Int. 2012 Oct;110(8 Pt B):E409-414.
1493 Piotr Wlaz, et al. Differential effects of glycine on the anticonvulsant activity of D-cycloserine and L-701,324 in mice. Pharmacological Reports 2011,63,1231-1234
1494 Gabbita SP, et al. Increased nuclear DNA oxidation in the brain in Alzheimer's disease.
1495 Cysewski P, et al. Theoretical description of the coding potential of diamino-5-formamidopyrimidines. Z Naturforsch C J Biosci. 1999 Mar-Apr;54(3-4):239-45.
1496 Lee SH, et al. A rapid and sensitive method for quantitation of nucleosides in human urine using liquid chromatography/mass spectrometry with direct urine injection. Rapid Commun Mass Spectrom. 2004;18(9):973-7.
1497 Periodic Reporting for period 1-AMPK-DIAB (A small molecule AMP activated protein kinase (AMPK) activator, denoted O304, as a novelinnovative drug for the treatment of type 2 diabetes).
1498 J Chem Soc 1938:439; Biochem J 39:308 (1945)
1499 Chuang LF, et al. Activation of human leukemia protein kinase C by tumor promoters and its inhibition by N-trifluoroacetyladriamycin-14-valerate (AD 32). Biochem Pharmacol. 1992 Feb 18;43(4):865-72.
1500 Wani MK, et al. Rationale for intralesional valrubicin in chemoradiation of squamous cell carcinoma of the head and neck. Laryngoscope. 2000 Dec;110(12):2026-32.
1501 Hauge E, et al. Topical valrubicin application reduces skin inflammation in murine models. Br J Dermatol. 2012 Aug;167(2):288-95.
1502 Lee SY, et al. Vanillin attenuates negative effects of ultraviolet A on the stemness of human adipose tissue-derived mesenchymal stem cells. Food Chem Toxicol. 2016 Oct;96:62-9.
1503 Xu J, et al. Vanillin-induced amelioration of depression-like behaviors in rats by modulating monoamine neurotransmitters in the brain. Psychiatry Res. 2015 Feb 28;225(3):509-14.
1504 Zhang T, et al. A small molecule targeting myoferlin exerts promising anti-tumor effects on breast cancer. Nat Commun. 2018 Sep 13;9(1):3726.
1505 Halestrap AP. The mitochondrial pyruvate carrier. Kinetics and specificity for substrates and inhibitors. Biochem J. 1975 April; 148(1): 85-96.
1506 Wiemer EA, et al. The inhibition of pyruvate transport across the plasma membrane of the bloodstream form of Trypanosoma brucei and its metabolic implications. Biochem J. 1995 Dec 1;312 ( Pt 2):479-84.
1507 Hinoi E, et al. A molecular mechanism of pyruvate protection against cytotoxicity of reactive oxygen species in osteoblasts. Mol Pharmacol. 2006 Sep;70(3):925-35. Epub 2006 Jun 9.
1508 Patterson JN, et al. Mitochondrial metabolism of pyruvate is essential for regulating glucose-stimulated secretion. J Biol Chem. 2014 May 9;289(19):13335-46.
1509 Zhong Y, et al. Application of mitochondrial pyruvate carrier blocker UK5099 creates metabolic reprogram and greater stem-like properties in LnCap prostate cancer cells in vitro. Oncotarget. 2015 Nov 10;6(35):37758-69.
1510 Li WW, et al. Discovery of the novel potent and selective FLT3 inhibitor 1-{5-[7-(3- morpholinopropoxy)quinazolin-4-ylthio]-[1,3,4]thiadiazol-2-yl}-3-p-tolylurea and its anti-acute myeloid leukemia (AML) activities in vitro and in vivo. J Med Chem. 2012 Apr 26;55(8):3852-66.
1511 Morand OH, et al. Ro 48-8.071, a new 2,3-oxidosqualene:lanosterol cyclase inhibitor lowering plasma cholesterol in hamsters, squirrel monkeys, and minipigs: comparison to simvastatin. J Lipid Res. 1997 Feb;38(2):373-90.
1512 Liang Y, et al. Cholesterol biosynthesis inhibitor RO 48-8071 suppresses growth of hormone-dependent and castration-resistant prostate cancer cells. Onco Targets Ther. 2016 May 30;9:3223-32
1513 Liang Y, et al. Cholesterol biosynthesis inhibitors as potent novel anti-cancer agents: suppression of hormone-dependent breast cancer by the oxidosqualene cyclase inhibitor RO 48-8071. Breast Cancer Res Treat. 2014 Jul;146(1):51-62.
1514 Chuang JC, et al. Sustained and selective suppression of intestinal cholesterol synthesis by Ro 48-8071, an inhibitor of 2,3-oxidosqualene:lanosterol cyclase, in the BALB/c mouse. Biochem Pharmacol. 2014 Apr 1;88(3):351-63.
1515 J. Chem. Res. Synop. 1977: 154
1516 Bymaster FP, et al. Pharmacological characterization of the norepinephrine and dopamine reuptake inhibitor EB-1020: implications for treatment of attention-deficit hyperactivity disorder. Synapse. 2012 Jun;66(6):522-32.
1517 Baron BM, et al. Pharmacological characterization of MDL 105,519, an NMDA receptor glycine site antagonist. Eur J Pharmacol. 1997 Apr 4;323(2-3):181-92.
1518 Butler KV, et al. Rational design and simple chemistry yield a superior, neuroprotective HDAC6 inhibitor, tubastatin A. J Am Chem Soc. 2010 Aug 11;132(31):10842-6.
1519 Hideshima T, et al. Small-molecule inhibition of proteasome and aggresome function induces synergistic antitumor activity in multiple myeloma. Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8567-72. Epub 2005 Jun 3.
1520 Lu CY, et al. Tubacin, an HDAC6 Selective Inhibitor, Reduces the Replication of the Japanese Encephalitis Virus via the Decrease of Viral RNA Synthesis. Int J Mol Sci. 2017 May 1;18(5).
1521 J Soc Chem Ind 53:956 (1934)
1522 Dowarah R, et al. Selection and characterization of probiotic lactic acid bacteria and its impact on growth, nutrient digestibility, health and antioxidant status in weaned piglets. PLoS One. 2018 Mar 8;13(3):e0192978.
1523 Zhang Y, et al. Baseline sensitivity and resistance risk assessmemt of Rhizoctonia cerealis to thifluzamide, a succinate dehydrogenase inhibitor. Pestic Biochem Physiol. 2015 Oct;124:97-102.
1524 Yang Y, et, al. Thifluzamide affects lipid metabolism in zebrafish (Danio reio). Sci Total Environ. 2018 Aug 15;633:1227-1236.
1525 Neil Anthony Pegg, et al. Pharmaceutical compounds. WO2018073586A1.
1526 Biochim Biophys Acta 201:453 !970); J Pharmacol Exp Therap 190:570 (1974); Trans IRE Professionsl Group 7:414 (2011)
1527 Eur J Pharmacol 57:107 (1979); 91:343 (1983; Am J Cardiol 51:1364 (1983)
1528 https://trialsearch.who.int/Trial2.aspx?TrialID=DRKS00021573; https://clinicaltrials.gov/ct2/results?cond=Covid19&term=PANTOPRAZOLE&cntry=&state=&city=&dist=
1529 Gen Pharmacol 30:639 (1998); Expert Opin Invest Drugs 11:117 (2002)
1530 Edouard Mullarky et al. Identification of a small molecule inhibitor of 3-phosphoglycerate dehydrogenase to target serine biosynthesis in cancers&#x0D; Proc Natl Acad Sci U S A, 2016 Feb 16, 113(7):1778-83.
1531 Conroy MC, et al. Pharmacology, pharmacokinetics, and therapeutic use of meclofenamate sodium. Clin J Pain. 1991;7 Suppl 1:S44-8.
1532 Eleftheriou CG, et al. Meclofenamic acid improves the signal to noise ratio for visual responses produced by ectopicexpression of human rod opsin. Mol Vis. 2017 Jun 16;23:334-345. eCollection 2017.
1533 Huang Y, et al. Meclofenamic acid selectively inhibits FTO demethylation of m6A over ALKBH5. Nucleic Acids Res. 2015 Jan;43(1):373-84.
1534 Chem Abstracts 41: 4455 (1947); Eur J Pharmacol 177 215 (1990); Br J Pharmacol 124:386 (1998)
1535 Kazuki Yoshida, et al. P2X7 receptor antagonist activity of the anti-allergic agent oxatomide. Eur J Pharmacol. 2015 Nov 15;767:41-51.
1536 K Ohmori, et al. Pharmacological studies on oxatomide (KW-4354). (7) Antagonistic effects on chemical mediators. Nihon Yakurigaku Zasshi. 1983 May;81(5):399-409.
1537 Lin WH, et al. BPR1J-097, a novel FLT3 kinase inhibitor, exerts potent inhibitory activity against AML. Br J Cancer. 2012 Jan 31;106(3):475-81.
1538 Chen CR et al. Gracillin induces apoptosis in HL60 human leukemic cell line via oxidative stress and cell cycle arrest of G1. Pharmazie. 2015 Mar;70(3):199-204.
1539 Harald Engelhardt, et al. New phenylpyrazolylacetamide compounds and derivatives as cdk8/cdk19 inhibitors.
1540 Pyruvate kinase activators for use in therapy. WO2012151451A1.
1541 https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=L-Carnitine&cntry=&state=&city=&dist=
1542 Acta Cryst C 48:741 (1992)
1543 Kurtzberg LS, et al. Genz-644282, a novel non-camptothecin topoisomerase I inhibitor for cancer treatment. Clin Cancer Res. 2011 May 1;17(9):2777-87.
1544 Houghton PJ, et al. Testing of the topoisomerase 1 inhibitor Genz-644282 by the pediatric preclinical testing program. Pediatr Blood Cancer. 2012 Feb;58(2):200-9.
1545 Sooryakumar D, et al. Molecular and cellular pharmacology of the novel noncamptothecin topoisomerase I inhibitor Genz-644282. Mol Cancer Ther. 2011 Aug;10(8):1490-9.
1546 Regul Toxicol Pharmacol 34:287 (2001); Cosmet Toiletries 118:47 (2003)
1547 Zaihui Zhang, et al. Heteropolycyclic inhibitors of protein kinases. US7196083B2.
1548 Woolley ML, et al. Evaluation of the pro-cognitive effects of the AMPA receptor positive modulator, 5-(1-piperidinylcarbonyl)-2,1,3-benzoxadiazole (CX691), in the rat. Psychopharmacology (Berl). 2009 Jan;202(1-3):343-54.
1549 Wezenberg E, et al. Acute effects of the ampakine farampator on memory and information processing in healthy elderly volunteers. Neuropsychopharmacology. 2007 Jun;32(6):1272-83.
1550 https://clinicaltrials.gov/ct2/show/NCT03376854?term=Vecuronium&cond=Covid19&draw=2&rank=1
1551 Fraser C, et al. Rapid Discovery and Structure-Activity Relationships of Pyrazolopyrimidines That Potently Suppress Breast Cancer Cell Growth via SRC Kinase Inhibition with Exceptional Selectivity over ABL Kinase. J Med Chem. 2016 May 26;59(10):4697-710.
1552 Scheuermann TH, et al. Allosteric inhibition of hypoxia inducible factor-2 with small molecules. Nat Chem Biol. 2013 Apr;9(4):271-6.
1553 Senavirathna LK, et al. Hypoxia induces pulmonary fibroblast proliferation through NFAT signaling. Sci Rep. 2018 Feb 9;8(1):2709.
1554 Navarrete C, et al. Hypoxia mimetic activity of VCE-004.8, a cannabidiol quinone derivative: implications for multiple sclerosis therapy. J Neuroinflammation. 2018 Mar 1;15(1):64.
1555 Palomares B, et al. VCE-004.8, A Multitarget Cannabinoquinone, Attenuates Adipogenesis and Prevents Diet-Induced Obesity. Sci Rep. 2018 Oct 31;8(1):16092.
1556 Bello E, et al. E-3810 is a potent dual inhibitor of VEGFR and FGFR that exerts antitumor activity in multiple preclinical models. Cancer Res. 2011 Feb 15;71(4):1396-405.
1557 Colzani M, et al. Quantitative chemical proteomics identifies novel targets of the anti-cancer multi-kinase inhibitor E-3810. Mol Cell Proteomics. 2014 Jun;13(6):1495-509.
1558 Bello E, et al. The tyrosine kinase inhibitor E-3810 combined with NSC 125973 inhibits the growth of advanced-stage triple-negative breast cancer xenografts. Mol Cancer Ther. 2013 Feb;12(2):131-40
1559 J Pharmacol Exp Ther 58:337 (1936); Eur J Respir Dis 64 Suppl 128:417 (1983); Am J Opthalmol 107:7 (1989)
1560 Kim SH, et al. Icilin induces G1 arrest through activating JNK and p38 kinase in a TRPM8-independent manner. Biochem Biophys Res Commun. 2011 Mar 4;406(1):30-5.
1561 Frank J P Kühn, et al. Inhibition of TRPM8 by icilin distinct from desensitization induced by menthol and menthol derivatives. J Biol Chem. 2009 Feb 13;284(7):4102-11.
1562 Liang F, et al. Darusentan is a potent inhibitor of endothelin signaling and function in both large and small arteries. Can J Physiol Pharmacol. 2010 Aug;88(8):840-9.
1563 Frank Enseleit, et al. Darusentan, a selective endothelin A receptor antagonist, for the oral treatment of resistant hypertension. Ther Adv Cardiovasc Dis. 2010 Aug;4(4):231-40.
1564 H H Dao, et al. Norepinephrine-induced aortic hyperplasia and extracellular matrix deposition are endothelin-dependent. J Hypertens. 2001 Nov;19(11):1965-73.
1565 Pediatr Neurol 9:465 (1993); J Forensic Sci 40:382 (1995); Am J Psychiatry 155:1339 (1998); Int Clin Psychopharmacol 18:101 (2003)
1566 Tetrahedron Letters 1967:2737
1567 Ratia, K., et al., A noncovalent class of papain-like protease/deubiquitinase inhibitors blocks SARS virus replication. Proc Natl Acad Sci U S A, 2008. 105(42): p. 16119-24.
1568 http://www.google.com/patents/WO2010022355A1cl=en
1569 Brendan T Freitas, et al. Characterization and Noncovalent Inhibition of the Deubiquitinase and deISGylase Activity of SARS-CoV-2 Papain-Like Protease. ACS Infect Dis. 2020 May 19.
1570 O'Malley DP, et al. Discovery of Pyridazinone and Pyrazolo[1,5-a]pyridine Inhibitors of C-Terminal Src Kinase. ACS Med Chem Lett. 2019 Sep 25;10(10):1486-1491.
1571 https://clinicaltrials.gov/ct2/show/NCT04467931?term=FUROSEMIDE&cond=Covid19&draw=2&rank=2 https://clinicaltrials.gov/ct2/show/NCT04556864?term=FUROSEMIDE&cond=Covid19&draw=2&rank=3 https://clinicaltrials.gov/ct2/show/NCT04278404?term=FUROSEMIDE&cond=Covid19&draw=2&rank=4
1572 Indian J Chem B 15:94 (1977)
1573 Kawaharada S, et al. ONO-8590580, a Novel GABAAα5 Negative Allosteric Modulator Enhances Long-Term Potentiation and Improves Cognitive Deficits in Preclinical Models. J Pharmacol Exp Ther. 2018 Jul;366(1):58-65.
1574 J Chem Soc 1939:925; Nat Prod Res 26:291 (2012)
1575 J Biol Chem 254:7558 (1979); 257:13704 (1982); Bone Marrow Transplant 30:135 (2002)
1576 ML418, et al. ML418: The First Selective, Sub-Micromolar Pore Blocker of Kir7.1 Potassium Channels. ACS Chem Neurosci. 2016 Jul 20;7(7):1013-23.
1577 Nijampatnam B, et al. Recent advances in the development of HBV capsid assembly modulators. Curr Opin Chem Biol. 2019 Jun;50:73-79.
1578 JAMA 282:1344 (1999); Drugs Aging 13:83 (1998)
1579 Tille JC, et al. Vascular endothelial growth factor (VEGF) receptor-2 antagonists inhibit VEGF- and basicfibroblast growth factor-induced angiogenesis in vivo and in vitro. J Pharmacol Exp Ther. 2001 Dec;299(3):1073-85.
1580 Daniel E. Jeffries, et al. Discovery of VU6015929: A Selective Discoidin Domain Receptor 1/2 (DDR1/2) Inhibitor to Explore the Role of DDR1 in Antifibrotic Therapy. ACS Med. Chem. Lett. 2019.
1581 Islam I, et al. Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 2: optimization of BX-517. Bioorg Med Chem Lett. 2007 Jul 15;17(14):3819-25.
1582 Islam I, et al. Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 1: design, synthesis and biological activity. Bioorg Med Chem Lett. 2007 Jul 15;17(14):3814-8.
1583 Groth C, et al. Pharmacological analysis of Drosophila melanogaster gamma-secretase with respect to differential proteolysis of Notch and APP. Mol Pharmacol. 2010 Apr;77(4):567-74.
1584 Fuwa H, et al. Divergent synthesis of multifunctional molecular probes to elucidate the enzyme specificity of dipeptidic gamma-secretase inhibitors. ACS Chem Biol. 2007 Jun 15;2(6):408-18.
1585 Zheng YH, et al. Notch γ-secretase inhibitor dibenzazepine attenuates angiotensin II-induced abdominal aortic aneurysm in ApoE knockout mice by multiple mechanisms. PLoS One. 2013 Dec 16;8(12):e83310.
1586 Xiao Z, et al. The Notch γ-secretase inhibitor ameliorates kidney fibrosis via inhibition of TGF-β/Smad2/3 signaling pathway activation. Int J Biochem Cell Biol. 2014 Oct;55:65-71.
1587 Xu F, et al. Beneficial health effects of lupenone triterpene: A review. Biomed Pharmacother. 2018 Jul;103:198-203.
1588 Xu F, et al. Lupenone is a good anti-inflammatory compound based on the network pharmacology. Mol Divers. 2019 Feb 22.
1589 Derenzini E, et al. The JAK inhibitor AZD1480 regulates proliferation and immunity in Hodgkin lymphoma. Blood Cancer J. 2011 Dec;1(12):e46.
1590 Scuto A, et al. The novel JAK inhibitor AZD1480 blocks STAT3 and FGFR3 signaling, resulting in suppression of human myeloma cell growth and survival. Leukemia. 2011 Mar;25(3):538-50.
1591 McFarland BC, et al. Therapeutic potential of AZD1480 for the treatment of human glioblastoma. Mol Cancer Ther. 2011 Dec;10(12):2384-93.
1592 Xin H, et al. Antiangiogenic and antimetastatic activity of JAK inhibitor AZD1480. Cancer Res. 2011 Nov 1;71(21):6601-10.
1593 Hedvat M, et al. The JAK2 inhibitor AZD1480 potently blocks Stat3 signaling and oncogenesis in solid tumors. Cancer Cell. 2009 Dec 8;16(6):487-9
1594 Ni J, et al. Tyrosine receptor kinase B is a drug target in astrocytomas. Neuro Oncol. 2017 Jan;19(1):22-30.
1595 Chin Med J 113:948 (2000); Curr Opin Neurobiol. 11:327 (2001); Curr Opin Pharmacol 7: 39 (2007)
1596 Matthews R, et al. Tc-99m mebrofenin hepatobiliary scan in obstructive hepatobiliary disease: determining causes with early and late delayed imaging. World J Nucl Med. 2013 May;12(2):54-6.
1597 Morandi F, et al. Transsplenic portal scintigraphy using 99mTc-mebrofenin in normal dogs. Vet Radiol Ultrasound. 2007 May-Jun;48(3):286-91.
1598 de Graaf W, et al. Transporters involved in the hepatic uptake of (99m)Tc-mebrofenin and indocyanine green. J Hepatol. 2011 Apr;54(4):738-45.
1599 Zhu J, et al. Synthesis, molecular modeling, and biological evaluation of novel RAD51 inhibitors. Eur J Med Chem. 2015;96:196-208.
1600 Jiewen Zhu, et al. A novel small molecule RAD51 inactivator overcomes imatinib-resistance in chronic myeloid leukaemia. EMBO Mol Med. 2013 Mar;5(3):353-65.
1601 Maxime Rossi , Silodosin in the treatment of benign prostatic hyperplasia. Drug Des Devel Ther. 2010; 4: 291–297.
1602 Villa L, et al. Effects by silodosin on the partially obstructed rat ureter in vivo and on human and rat isolated ureters.Br J Pharmacol. 2013 May;169(1):230-8.
1603 Osman NI, et al.Silodosin : a new subtype selective alpha-1 antagonist for the treatment of lower urinary tract symptoms in patients with benign prostatic hyperplasia.Expert Opin Pharmacother. 2012 Oct;13(14):2085-96.
1604 Kawahara T, et al. Silodosin inhibits the growth of bladder cancer cells and enhances the cytotoxic activity of cisplatin via ELK1 inactivation.Am J Cancer Res. 2015 Sep 15;5(10):2959-68. eCollection 2015.
1605 Expert Opin. Drug Metab. Toxicol. (2010), 6(8), 919-938; J. Med. Chem. (1974), 17(11), 1237-9; Chem. Pharm. Bull. (1977), 25(8), 1877-91
1606 Teng X, Keys H, Jeevanandam A, Structure-activity relationship study of [1,2,3]thiadiazole necroptosis inhibitors. Bioorg Med Chem Lett. 2007 Dec 15;17(24):6836-40.
1607 Jagtap PG, Degterev A, Choi S, Structure-activity relationship study of tricyclic necroptosis inhibitors. J Med Chem. 2007 Apr 19;50(8):1886-95.
1608 Teng X, Degterev A, Jagtap P, Structure-activity relationship study of novel necroptosis inhibitors. Bioorg Med Chem Lett. 2005 Nov 15;15(22):5039-44.
1609 Takahashi N, et al. Necrostatin-1 analogues: critical issues on the specificity, activity and in vivo use in experimental disease models. Cell Death Dis. 2012 Nov 29;3:e437.
1610 J. Pharm. Pharmacol. (1982), 34(6), 391-4; Acta Univ. Palacki. Olomuc., Fac. Med. (1973), 67, 155-92; Antidepressant Drugs, Proc. Int. Symp., 1st (1967), 208-16
1611 Experientia 30:1265 (1974)
1612 Fraxin (50 mg/kg, p.o.) significantly blocks the CCl&lt;sub&gt;4&lt;/sub&gt;-induced elevation of ALT and AST. Fraxin (10 and 50 mg/kg, p.o.) significantly reduces the GSSG levels (1.7±0.3 and 1.5±0.2 nM/g liver, respectively) compared with the GSSG levels of the CCl&lt;sub&gt;4&lt;/sub&gt;-treated group&lt;sup&gt;
1613 &lt;/sup&gt;.
1614 Whang WK, et al. Natural compounds,fraxin and chemicals structurally related to fraxin protect cells from oxidative stress. Exp Mol Med. 2005 Oct 31;37(5):436-46.
1615 Balmus G, et al. Targeting of NAT10 enhances healthspan in a mouse model of human accelerated aging syndrome. Nat Commun. 2018;9(1):1700. Published 2018 Apr 27.
1616 Liu H, et al. DNA damage induces N-acetyltransferase NAT10 gene expression through transcriptional activation. Mol Cell Biochem. 2007;300(1-2):249-258.
1617 Ma R, et al. Up regulation of NAT10 promotes metastasis of hepatocellular carcinoma cells through epithelial-to-mesenchymal transition. Am J Transl Res. 2016;8(10):4215-4223. Published 2016 Oct 15.
1618 Farrell DJ, et al. In Vitro Activity of Gepotidacin (GSK2140944) against Neisseria gonorrhoeae. Antimicrob Agents Chemother. 2017 Feb 23;61(3).
1619 Biedenbach DJ, et al. In Vitro Activity of Gepotidacin, a Novel Triazaacenaphthylene Bacterial Topoisomerase Inhibitor, against a Broad Spectrum of Bacterial Pathogens. Antimicrob Agents Chemother. 2016 Jan 4;60(3):1918-23.
1620 O'Riordan W, et al. Efficacy, Safety, and Tolerability of Gepotidacin (GSK2140944) in the Treatment of Patients with Suspected or Confirmed Gram-Positive Acute Bacterial Skin and Skin Structure Infections. Antimicrob Agents Chemother. 2017 May 24;61(6).
1621 So W, et al. Pharmacodynamic Profile of GSK2140944 against Methicillin-Resistant Staphylococcus aureus in a Murine Lung Infection Model. Antimicrob Agents Chemother. 2015 Aug;59(8):4956-61.
1622 Purich D. The Inhibitor Index A Desk Reference on Enzyme Inhibitors, Receptor Antagonists, Drugs, Toxins, Poisons, Biologics, and Therapeutic Leads. ISBN 9781138739215
1623 Wang Z, et al. Inhibition of H3K4 demethylation induces autophagy in cancer cell lines. Biochim Biophys Acta. 2017 Aug 8;1864(12):2428-2437.
1624 Bull Soc Chim France 4L1265 (1937); Phytochemistry 12:193 (1973); 13:1628 (1974); J Nat Prod 39:175,197 (1976); 45:277 (1982)
1625 Georgievska B, et al. AZD1080, a novel GSK3 inhibitor, rescues synaptic plasticity deficits in rodent brain and exhibits peripheral target engagement in humans. J Neurochem. 2013 May;125(3):446-56.
1626 Kraus JM, et al. Rational modification of a candidate cancer drug for use against Chagas disease. J Med Chem. 2009 Mar 26;52(6):1639-47.
1627 Stellavato A, et al. Myclobutanil worsens nonalcoholic fatty liver disease: An in vitro study of toxicity and apoptosis on HepG2 cells. Toxicol Lett. 2016 Nov 16;262:100-104.
1628 Volberg T, et al. The effect of tyrosine-specific protein phosphorylation on the assembly of adherens-type junctions. EMBO J. 1992 May;11(5):1733-42.
1629 Wessely O, et al. Distinct roles of the receptor tyrosine kinases c-ErbB and c-Kit in regulating the balance between erythroid cell proliferation and differentiation. Cell Growth Differ. 1997 May;8(5):481-93.
1630 Banerjee S, et al. Epidermal growth factor induces WISP-2/CCN5 expression in estrogen receptor-alpha-positive breast tumor cells through multiple molecular cross-talks. Mol Cancer Res. 2005 Mar;3(3):151-62.
1631 ARYL SULFONOHYDRAZIDES. WO 2013041119 A1.
1632 Halland N, et al. Discovery of N-[4-(1H-Pyrazolo[3,4-b]pyrazin-6-yl)-phenyl]-sulfonamides as Highly Active and Selective SGK1 Inhibitors. ACS Med Chem Lett. 2014 Oct 23;6(1):73-8.
1633 J Vet Med Sci 65:1275 (2003)|
1634 Chen Q, et al. Investigation of the genotoxicity of quinocetone, carbadox and olaquindox in vitro using Vero cells. Food Chem Toxicol. 2009 Feb;47(2):328-34.
1635 Looft T, et al. Carbadox has both temporary and lasting effects on the swine gut microbiota. Front Microbiol. 2014 Jun 10;5:276.
1636 Lara E, et al. Salermide, a Sirtuin inhibitor with a strong cancer-specific proapoptotic effect. Oncogene. 2009 Feb 12;28(6):781-91.
1637 Chen H, et, al. Metabolism of ginger component
1638 -shogaol in liver microsomes from mouse, rat, dog, monkey, and human. Mol Nutr Food Res. 2013 May;57(5):865-76.
1639 Zhu Y, et, al. Synthesis, evaluation, and metabolism of novel
1640 -shogaol derivatives as potent Nrf2 activators. Free Radic Biol Med. 2016 Jun;95:243-54.
1641 https://clinicaltrials.gov/ct2/show/NCT04706416?term=N-Acetyl-D-glucosamine&cond=covid&draw=2&rank=1
1642 Floresta G, et al. Development of new HO-1 inhibitors by a thorough scaffold-hopping analysis. Bioorg Chem. 2018 Dec;81:334-339.
1643 Souers AJ, et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013 Feb;19(2):202-8.
1644 Peirs S, et al. ABT-199 mediated inhibition of BCL-2 as a novel therapeutic strategy in T-cell acute lymphoblastic leukemia. Blood. 2014 Dec 11;124(25):3738-47.
1645 Bi C, et al. Inhibition of 4EBP phosphorylation mediates the cytotoxic effect of mechanistic target of rapamycin kinase inhibitors in aggressive B-cell lymphomas. Haematologica. 2017 Apr;102(4):755-764.
1646 Zhang L, et al. Identification of compound CA-5f as a novel late-stage autophagy inhibitor with potent anti-tumor effect against non-small cell lung cancer. Autophagy. 2019 Mar;15(3):391-406.
1647 Shao S, et al. Spautin-1, a novel autophagy inhibitor, enhances imatinib-induced apoptosis in chronic myeloid leukemia. Int J Oncol. 2014 May;44(5):1661-1668.
1648 Xiao J, et al. Spautin-1 Ameliorates Acute Pancreatitis via Inhibiting Impaired Autophagy and Alleviating Calcium Overload. Mol Med. 2016 Aug 18;22.
1649 Nathans D, et al. Puromycin inhibition of protein synthesis: incorporation of puromycin intopeptide chains. Proc Natl Acad Sci U S A. 1964 Apr;51:585-92.
1650 Miyamoto-Sato E, et al. Specific bonding of puromycin to full-length protein at the C-terminus. Nucleic Acids Res. 2000 Mar 1;28(5):1176-82.
1651 Schmidt EK, et al. SUnSET, a nonradioactive method to monitor protein synthesis. Nat Methods. 2009 Apr;6(4):275-7.
1652 Southern Med J 50:1541 (1957)
1653 Wong KL, et al. Isosteviol acts on potassium channels to relax isolated aortic strips of Wistar rat. Life Sci. 2004 Mar 26;74(19):2379-87.
1654 Wong KL, et al. Isosteviol as a potassium channel opener to lower intracellular calcium concentrations in cultured aortic smooth muscle cells. Planta Med. 2004 Feb;70(2):108-12.
1655 Wong KL, et al. Antiproliferative effect of isosteviol on angiotensin-II-treated rat aortic smooth muscle cells. Pharmacology. 2006;76(4):163-9.
1656 Asad Ullah, et al. Bioactivity Profile of the Diterpene Isosteviol and its Derivatives. Molecules. 2019 Feb 14;24(4):678.
1657 Liang Y, et al. A novel selective LSD1/KDM1A inhibitor epigenetically blocks herpes simplex virus lytic replication and reactivation from latency. mBio. 2013 Feb 5;4(1):e00558-12.
1658 McEachern KA, et al. A specific and potent inhibitor of glucosylceramide synthase for substrate inhibition therapy ofGaucher disease. Mol Genet Metab. 2007 Jul;91(3):259-68.
1659 https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=Tofacitinib+&cntry=&state=&city=&dist=&Search=Search
1660 Luo C, et al. Inhibition of matrine against gastric cancer cell line MNK45 growth and its anti-tumor mechanism. Mol Biol Rep. 2012 May;39(5):5459-64.
1661 Tan C, et al. Matrine induction of reactive oxygen species activates p38 leading to caspase-dependent cell apoptosis in non-small cell lung cancer cells. Oncol Rep. 2013 Nov;30(5):2529-35.
1662 Li X, et al. Regulation of endothelial nitric oxide synthase and asymmetric dimethylarginine by matrine attenuates isoproterenol-induced acute myocardial injury in rats. J Pharm Pharmacol. 2012 Aug;64(8):1107-18.
1663 Zhang B, et al. Antiinflammatory effects of matrine in LPS-induced acute lung injury in mice. Eur J Pharm Sci. 2011 Dec 18;44(5):573-9. |J Nat Prod 44:236 (1981); J Agric Food Chem 39:189 (1991); J Forestry Res 17:323 (2006); Basic Clin Pharmacol Toxicol 107:906 (2010)
1664 Fr. (1969), FR 1581285 19690912
1665 Skin Pharmacol 3:1 (1990); Clin Dermatol 15:723 (1997)
1666 https://clinicaltrials.gov/ct2/show/NCT04456439?term=PROMETHAZINE&cond=Covid19&draw=2&rank=1
1667 Carney DW, et al. Structural optimization of a retrograde trafficking inhibitor that protects cells from infections by human polyoma- and papillomaviruses. Bioorg Med Chem. 2014 Sep 1;22(17):4836-47.
1668 Beesley AH, et al. In vitro cytotoxicity of nelarabine, clofarabine and flavopiridol in paediatric acute lymphoblastic leukaemia. Br J Haematol. 2007 Apr;137(2):109-16.
1669 DeAngelo DJ, et al. Nelarabine induces complete remissions in adults with relapsed or refractory T-lineage acute lymphoblastic leukemia or lymphoblastic lymphoma: Cancer and Leukemia Group B study 19801. Blood. 2007 Jun 15;109(12):5136-42.
1670 https://clinicaltrials.gov/ct2/show/NCT04730206?term=Camostat&recrs=ab&cond=Covid19&phase=12&draw=2&rank=5
1671 Hasegawa M, et al. Analysis on blast fungus-responsive characters of a flavonoid phytoalexin sakuranetin; accumulation in infected rice leaves, antifungal activity and detoxification by fungus. Molecules. 2014 Aug 4;19(8):11404-18.
1672 Bittencourt-Mernak MI, et al. Prophylactic and therapeutic treatment with the flavonone sakuranetin ameliorates LPS-induced acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2017 Feb 1;312(2):L217-L230.
1673 Arch Surg 75:780 (1957)
1674 Tai X, et al. Cabazitaxel and indocyanine green co-delivery tumor-targeting nanoparticle for improved antitumor efficacy and minimized drug toxicity. J Drug Target. 2016 Sep 9:1-29.
1675 Gdowski AS, et al. Bone-targeted cabazitaxel nanoparticles for metastatic prostate cancer skeletal lesions and pain. Nanomedicine (Lond). 2017 Sep;12(17):2083-2095.
1676 Bender T, Bariska J, Rojkovich B, Bálint G. Etofenamate levels in human serum and synovial fluid following iontophoresis. Arzneimittelforschung. 2001;51(6):489-92.
1677 Fraga A, de Almeida M, Moreira-da-Silva V et al. Intramuscular Etofenamate versus Diclofenac in the Relief of Renal Colic : A Randomised, Single-Blind, Comparative Study. Clin Drug Investig. 2003;23(11):701-6.
1678 Joana Marto, et al. Topical gels of etofenamate: in vitro and in vivo evaluation. Pharm Dev Technol. 2015;20(6):710-5.
1679 Erba, F., et al., Selective inhibition of human mast cell tryptase by gabexate mesylate, an antiproteinase drug. Biochem Pharmacol, 2001. 61(3): p. 271-6.
1680 Aosasa, S., et al., Mechanism of the inhibitory effect of protease inhibitor on tumor necrosis factor alpha production of monocytes. Shock, 2001. 15(2): p. 101-5.
1681 Colasanti, M., et al., Effect of gabexate mesylate (FOY), a drug for serine proteinase-mediated diseases, on the nitric oxide pathway. Biochem Biophys Res Commun, 1998. 246(2): p. 453-6.
1682 Liu X, et al. Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity. Blood. 2010 Apr 29;115(17):3520-30.
1683 Koblish HK, et al. Hydroxyamidine inhibitors of indoleamine-2,3-dioxygenase potently suppress systemic tryptophan catabolism and the growth of IDO-expressing tumors. Mol Cancer Ther. 2010 Feb;9(2):489-98.
1684 Fu R, et al. LW106, a novel indoleamine 2,3-dioxygenase 1 inhibitor, suppresses tumour progression by limiting stroma-immune crosstalk and cancer stem cell enrichment in tumour micro-environment. Br J Pharmacol. 2018 Jul;175(14):3034-3049.
1685 J Biol Chem 162:630 (1946)
1686 Cho JY, et al. In vitro anti-inflammatory effects of cynaropicrin, a sesquiterpene lactone, from Saussurea lappa. Eur J Pharmacol. 2000 Jun 23;398(3):399-407.
1687 Masutani T, et al. Cynaropicrin is dual regulator for both degradation factors and synthesis factors in the cartilage metabolism. Life Sci. 2016 Aug 1;158:70-7.
1688 da Silva CF, et al. Activities of psilostachyin A and cynaropicrin against Trypanosoma cruzi in vitro and in vivo. Antimicrob Agents Chemother. 2013 Nov;57(11):5307-14.
1689 Mamand S, et al. Comparison of interleukin-2-inducible kinase (ITK) inhibitors and potential for combination therapies for T-cell lymphoma. Sci Rep. 2018 Sep 21;8(1):14216.
1690 https://clinicaltrials.gov/ct2/show/NCT04330300?term=Nicardipine&cond=covid&draw=2&rank=1
1691 https://clinicaltrials.gov/ct2/show/NCT04695197?term=Artemether&cond=COVID-19&draw=2&rank=1
1692 Zhang P, et al. Discovery of Betrixaban (PRT054021), N-(5-chloropyridin-2-yl)-2-(4-(N,N-dimethylcarbamimidoyl)benzamido)-5-methoxybenzamide, a highly potent, selective, and orally efficacious factor Xa inhibitor. Bioorg Med Chem Lett. 2009 Apr 15;19(8):21
1693 Lu G, et al. A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nat Med. 2013 Apr;19(4):446-51.
1694 Hatse S, et al. AMD3465, a monomacrocyclic CXCR4 antagonist and potent HIV entry inhibitor. Biochem Pharmacol. 2005 Sep 1;70(5):752-61.
1695 Yang L, et al. Blocking CXCR4-mediated cyclic AMP suppression inhibits brain tumor growth in vivo. Cancer Res. 2007 Jan 15;67(2):651-8.
1696 Ye XS, et al. A Novel Eg5 Inhibitor (LY2523355) Causes Mitotic Arrest and Apoptosis in Cancer Cells and Shows Potent Antitumor Activity in Xenograft Tumor Models. Mol Cancer Ther. 2015 Nov;14(11):2463-72.
1697 Brain 115:1249 (1992); Int J Tryptophan Res 5:1 (2012)
1698 Drugs (1988), 35(3), 187-91; Contraception (1987), 36 Suppl, 1-5; FEBS Lett. (1987), 217(2), 221-6|
1699 Jiang W, et al. New progesterone receptor antagonists: phosphorus-containing 11beta-aryl-substituted steroids. Bioorg Med Chem. 2006 Oct 1;14(19):6726-32.
1700 Jurado R, et al. NSC 119875 cytotoxicity is increased by mifepristone in cervical carcinoma: an in vitro and in vivo study. Oncol Rep. 2009 Nov;22(5):1237-45.
1701 Sharrett-Field L, et al. Mifepristone Pretreatment Reduces Ethanol Withdrawal Severity In Vivo. Alcohol Clin Exp Res. 2013 Aug;37(8):1417-23.
1702 Yuehua You, et al. Progesterone Promotes Endothelial Nitric Oxide Synthase Expression Through Enhancing Nuclear Progesterone receptor-SP1 Formation. Am J Physiol Heart Circ Physiol. 2020 Jul 3.
1703 Krennhrubec K, et al. Design and evaluation of 'Linkerless' hydroxamic acids as selective HDAC8 inhibitors. Bioorg Med Chem Lett. 2007 May 15;17(10):2874-8.
1704 Oehme I, et al. Histone deacetylase 8 in neuroblastoma tumorigenesis. Clin Cancer Res. 2009 Jan 1;15(1):91-9.
1705 C Huang, et al. Blocking activator protein-1 activity, but not activating retinoic acid response element, is required for the antitumor promotion effect of retinoic acid. Proc Natl Acad Sci U S A. 1997 May 27;94(11):5826-30.
1706 Bradley A Maron, et al. Upregulation of steroidogenic acute regulatory protein by hypoxia stimulates aldosterone synthesis in pulmonary artery endothelial cells to promote pulmonary vascular fibrosis. Circulation. 2014 Jul 8;130(2):168-79.
1707 Eunyoung Byun, et al. Activation of NF-κB and AP-1 Mediates Hyperproliferation by Inducing β-Catenin and c-Myc in Helicobacter pylori-Infected Gastric Epithelial Cells. Yonsei Med J. 2016 May;57(3):647-51.
1708 Ye Sun, et al. Inflammatory signals from photoreceptor modulate pathological retinal angiogenesis via c-Fos. J Exp Med. 2017 Jun 5;214(6):1753-1767.
1709 JACS 52:2538 (1930); J Enzym Inhib Med Chem 24:804 (2009)|Eur J Pharmacol 691:125 (2012)
1710 Can J Chem 34: 1562 (1956)
1711 Illendula A, et al. Chemical biology. A small-molecule inhibitor of the aberrant transcription factor CBFβ-SMMHC delays leukemia in mice. Science. 2015 Feb 13;347(6223):779-84.
1712 Zhao K, et al. Oroxylin A promotes PTEN-mediated negative regulation of MDM2 transcription via SIRT3-mediated deacetylation to stabilize p53 and inhibit glycolysis in wt-p53 cancer cells. J Hematol Oncol. 2015 Apr 23;8:41. http://www.ncbi.nlm.nih.gov/pubmed/25902914
1713 Dai Q, et al. Oroxylin A regulates glucose metabolism in response to hypoxic stress with the involvement of Hypoxia-inducible factor-1 in human hepatoma HepG2 cells. Mol Carcinog. 2015 Aug 10.
1714 Wei L, et al. Oroxylin A inhibits glycolysis-dependent proliferation of human breast cancer via promoting SIRT3-mediated SOD2 transcription and HIF1α destabilization. Cell Death Dis. 2015 Apr 9
1715 Wu Y, et al. ABMA, a small molecule that inhibits intracellular toxins and pathogens by interfering with late endosomal compartments.
1716 Wu Y, et al. DABMA: A Derivative of ABMA with Improved Broad-Spectrum Inhibitory Activity of Toxins and Viruses. ACS Med Chem Lett. 2019 Jul 2;10(8):1140-1147.
1717 Beck B, et al. Prospects for prostate cancer imaging and therapy using high-affinity TRPM8 activators. Cell Calcium. 2007 Mar;41(3):285-94.
1718 Morales C, et al. Antitumoral effect of irinotecan (CPT-11) on an experimental model of malignant neuroectodermal tumor. J Neurooncol. 2002 Feb;56(3):219-26.
1719 Pavillard V, et al. Determinants of the cytotoxicity of irinotecan in two human colorectal tumor cell lines. Cancer Chemother Pharmacol. 2002 Apr;49(4):329-35. Epub 2002 Jan 30.
1720 Allegrini G, et al. Thrombospondin-1 plus irinotecan: a novel antiangiogenic-chemotherapeutic combination that inhibits the growth of advanced human colon tumor xenografts in mice. Cancer Chemother Pharmacol. 2004 Mar;53(3):261-6. Epub 2003 Dec 5.
1721 Dela Cruz FS, et al. A case study of an integrative genomic and experimental therapeutic approach for rare tumors: identification of vulnerabilities in a pediatric poorly differentiated carcinoma. Genome Med. 2016 Oct 31;8(1):116.
1722 Huang MY, et al. Chemotherapeutic agent CPT-11 eliminates peritoneal resident macrophages by inducing apoptosis. Apoptosis. 2016 Feb;21(2):130-42. |Cancer Chemother. Pharmacol. (1995), 36(5), 393-403; Oncol. Res. (1993), 5(12), 467-74; Chem. Pharm. Bull. (1991), 39(6), 1446-54
1723 https://clinicaltrials.gov/ct2/show/NCT04946162?term=Tadalafil&cond=COVID-19&draw=2&rank=1
1724 Andreev IA, et al. Discovery of the 2-phenyl-4,5,6,7-Tetrahydro-1H-indole as a novel anti-hepatitis C virus targeting scaffold. Eur J Med Chem. 2015;96:250-8.
1725 N. Engl. J. Med. (1960), 263, 927-34; Antibiot. Annu. (1960), 776-84; J. Antimicrob. Chemother. (2000), 46(6), 917-9
1726 Li X et al. Fatostatin displays high antitumor activity in prostate cancer by blocking SREBP-regulated metabolic pathways and androgen receptor signaling. Mol Cancer Ther. 2014 Apr;13(4):855-66.
1727 Shao W et al. Fatostatin blocks ER exit of SCAP but inhibits cell growth in a SCAP-independent manner. J Lipid Res. 2016 Aug;57(8):1564-73.
1728 Inoue K et al. Fatostatin, an SREBP inhibitor, prevented RANKL-induced bone loss by suppression of osteoclast differentiation. Biochim Biophys Acta. 2015 Nov;1852(11):2432-41.
1729 Choi Y, et al. Identification of bioactive molecules by adipogenesis profiling of organic compounds. J Biol Chem. 2003 Feb 28;278(9):7320-4.
1730 Kamisuki S, et al. A small molecule that blocks fat synthesis by inhibiting the activation of SREBP. Chem Biol. 2009 Aug 28;16(8):882-92.
1731 Riv. Farmacol. Ter. (1982), 13(2), 111-22; Biochem. Pharmacol. (1976), 25(19), 2203-7; Atherosclerosis (1971), 14(3), 375-8
1732 Mijatovic T, et al. UNBS5162, a novel naphthalimide that decreases CXCL chemokine expression in experimental prostate cancers. Neoplasia. 2008 Jun;10(6):573-86.
1733 Tina Mahieu, et al. UNBS5162: A novel naphthalimide derivative with potent pro-autophagic effects in human cancer cells. Cancer Research, 2007 May; 67(9) Supplement.
1734 He D, et al. UNBS5162 inhibits the proliferation of esophageal cancer squamous cells via the PI3K/AKT signaling pathway. Mol Med Rep. 2018 Jan;17(1):549-555.
1735 J.Neurochem. 63 Suppl 1:S49A (1994); 65:96 (1995)
1736 Lanier M, et al. Structure-Based Design of ASK1 Inhibitors as Potential Agents for Heart Failure. ACS Med Chem Lett. 2017 Feb 8;8(3):316-320.
1737 Lin JH, et al. Design of a phase 2 clinical trial of an ASK1 inhibitor, GS-4997, in patients with diabetic kidney disease. Nephron. 2015;129(1):29-33.
1738 Loomba R, et al. The ASK1 inhibitor selonsertib in patients with nonalcoholic steatohepatitis: A randomized, phase 2trial. Hepatology. 2018 Feb;67(2):549-559.
1739 Yuan J, et al. Polo-box domain inhibitor poloxin activates the spindle assembly checkpoint and inhibits tumor growth in vivo.&#x0D; Am J Pathol. 2011 Oct;179(4):2091-9.
1740 Sanhaji M, et al. p53 is not directly relevant to the response of Polo-like kinase 1 inhibitors.&#x0D; Cell Cycle. 2012 Feb 1;11(3):543-53.
1741 Lee KS, et al. Pinning down the polo-box domain. Chem Biol. 2008 May;15(5):415-6.
1742 Reindl W, et al. Inhibition of polo-like kinase 1 by blocking polo-box domain-dependent protein-protein interactions. Chem Biol. 2008 May;15(5):459-66.
1743 Can Med Assoc J 80:785 (1959); Am J Hematol 46:138 (1994); Pharmacother 23:533 (2003)
1744 WZ811, et al. Discovery of small molecule CXCR4 antagonists. J Med Chem. 2007 Nov 15;50(23):5655-64.
1745 Li SH, et al. Suppression of chronic lymphocytic leukemia progression by CXCR4 inhibitor WZ811. Am J Transl Res. 2016 Sep 15;8(9):3812-3821.
1746 J Clin Pharmacol 20:213 (1980); Drugs 23:250 (1982)
1747 Adv. Pharmacol. Chemother. (1973), 11, 151-220; Lancet (1960), 2(7150), 564-7; Br. Med. J. (1960), 2, 694-9
1748 Chem Commun 1965:302
1749 Nicolle LE. Pivmecillinam in the treatment of urinary tract infections.&#x0D; J Antimicrob Chemother. 2000 Aug;46 Suppl A:35-39.
1750 Graninger W. Pivmecillinam--therapy of choice for lower urinary tract infection. Int J Antimicrob Agents. 2003 Oct;22 Suppl 2:73-8.
1751 Holme E, et al. Carnitine deficiency induced by pivampicillin and pivmecillinam therapy. Lancet. 1989 Aug 26;2(8661):469-73.
1752 Br. J. Pharmacol. (2005), 144(4), 538-550; Drugs (2004), 64(19), 2237-2246; Int. J. Clin. Pract. (2004), 58(6), 606-611
1753 Zhang Y, et al. Discovery and Characterization of XY101, a Potent, Selective, and Orally Bioavailable RORγ Inverse Agonist for Treatment of Castration-Resistant Prostate Cancer. J Med Chem. 2019 May 9;62(9):4716-4730.
1754 Tummala R K Reddy, et al.Three-dimensional Pharmacophore Design and Biochemical Screening Identifies Substituted 1,2,4-triazoles as Inhibitors of the Annexin A2-S100A10 Protein Interaction. ChemMedChem. 2012 Aug;7(8):1435-46.
1755 Andrew W Woodham, et al. Small Molecule Inhibitors of the Annexin A2 Heterotetramer Prevent Human Papillomavirus Type 16 Infection. J Antimicrob Chemother. 2015;70(6):1686-90.
1756 Pyonteck SM, et al. CSF-1R inhibition alters macrophage polarization and blocks glioma progression. Nat Med. 2013 Oct;19(10):1264-72.
1757 Strachan DC, et al. CSF1R inhibition delays cervical and mammary tumor growth in murine models by attenuating the turnover of tumor-associated macrophages and enhancing infiltration by CD8+ T cells. Oncoimmunology. 2013 Dec 1;2(12):e26968.
1758 J Antibiot 23:551, 559 (1970); Drugs 27:548 (1984)
1759 Sanches M, et al. Structure and mechanism of action of the hydroxy-aryl-aldehyde class of IRE1 endoribonuclease inhibitors. Nat Commun. 2014 Aug 28;5:4202.
1760 Wang Y, et al. Selective identification of hedgehog pathway antagonists by direct analysis of smoothened ciliary translocation . ACS Chem Biol. 2012,15;7(6):1040-8.
1761 Yamamoto T, et al. Estrogen-related receptor-γ regulates estrogen receptor-α responsiveness in uterine endometrial cancer. Int J Gynecol Cancer. 2012;22(9):1509-16.
1762 Yu S, et al. ERRgamma suppresses cell proliferation and tumor growth of androgen-sensitive and androgen-insensitive prostate cancer cells and its implication as a therapeutic target for prostate cancer. Cancer Res. 2007;67(10):4904-14.
1763 Donna D. Yu, Barry Marc Forman. Identification of an agonist ligand for estrogen-related receptors ERRβ/γ. Bioorganic &amp; Medicinal Chemistry Letters. 2005,15(5): 1311-1313.
1764 A Pacwa, et al. Interplay between estrogen-related receptors and steroidogenesis-controlling molecules in adrenals. In vivo and in vitro study. Acta Histochem. 2018 Jul;120(5):456-467.
1765 Casado J, et al. Alternated quinoid/aromatic units in terthiophenes building blocks for electroactive narrow band gap polymers. Extended spectroscopic, solid state, electrochemical, and theoretical study. J Phys Chem B. 2005 Sep 8;109(35):16616-27.
1766 Boschelli DH, et al. Optimization of 4-phenylamino-3-quinolinecarbonitriles as potent inhibitors of Src kinase activity. J Med Chem, 2001, 44(23), 3965-3977.
1767 Golas JM, et al. SKI-606, a 4-anilino-3-quinolinecarbonitrile dual inhibitor of Src and Abl kinases, is a potent antiproliferative agent against chronic myelogenous leukemia cells in culture and causes regression of K562 xenografts in nude mice. Cancer Res, 2003, 63(2), 375-381.
1768 Vultur A, et al. SKI-606 (bosutinib), a novel Src kinase inhibitor, suppresses migration and invasion of human breast cancer cells. Mol Cancer Ther, 2008, 7(5), 1185-1194.
1769 Golas JM, et al. SKI-606, a Src/Abl inhibitor with in vivo activity in colon tumor xenograft models. Cancer Res, 2005, 65(12), 5358-5364.
1770 Mol Pharmacol 54: 162 (1998)
1771 Lai MT et al. In vitro characterization of MK-1439, a novel HIV-1 nonnucleoside reverse transcriptase inhibitor. Antimicrob Agents Chemother. 2014;58(3):1652-63.
1772 Anderson MS et al. Safety, tolerability and pharmacokinetics of doravirine, a novel HIV non-nucleoside reverse transcriptase inhibitor, after single and multiple doses in healthy subjects. Antivir Ther. 2015;20(4):397-405.
1773 Matsuda H, et al. Effects of nitroglycerin, adenosine, noradrenaline, and isoproterenol on the myocardial oxygen tension. Jpn Heart J. 1979 Nov;20(6):867-79.
1774 J. Steroid Biochem. Mol. Biol. (1994), 49(4-6), 261-7; Science (1958), 128, 478-80; Experientia (1958), 14, 151-2
1775 Chem Ber 103:3752 (1970); Chemistry in Sri Lanka 14:17 (1997)
1776 One class has the naphthalene second dione compounds and its derivative of protease modification activities. CN107163044A.
1777 Agents Actions 15:627 (1984)
1778 https://clinicaltrials.gov/ct2/show/NCT04768179?term=ASPIRIN&cond=Covid19&draw=2&rank=1 https://clinicaltrials.gov/ct2/show/NCT04365309?term=ASPIRIN&cond=Covid19&draw=2&rank=2 https://clinicaltrials.gov/ct2/show/NCT04808895?term=ASPIRIN&cond=Covid19&draw=2 https://clinicaltrials.gov/ct2/show/NCT04410328?term=ASPIRIN&cond=Covid19&draw=2 https://clinicaltrials.gov/ct2/show/NCT04937088?term=ASPIRIN&cond=Covid19&draw=2&rank=5 https://clinicaltrials.gov/ct2/show/NCT04466670?term=ASPIRIN&cond=Covid19&draw=2&rank=6 https://clinicaltrials.gov/ct2/show/NCT04363840?term=ASPIRIN&cond=Covid19&draw=2&rank=8 https://clinicaltrials.gov/ct2/show/NCT04425863?term=ASPIRIN&cond=Covid19&draw=2&rank=9 https://clinicaltrials.gov/ct2/show/NCT04498273?term=ASPIRIN&cond=Covid19&draw=2&rank=10 https://clinicaltrials.gov/ct2/show/NCT04368377?term=ASPIRIN&cond=Covid19&draw=2&rank=11 https://clinicaltrials.gov/ct2/show/NCT04324463?term=ASPIRIN&cond=Covid19&draw=2 https://clinicaltrials.gov/ct2/show/NCT04333407?term=ASPIRIN&cond=Covid19&draw=2&rank=14 https://clinicaltrials.gov/ct2/show/NCT04703608?term=ASPIRIN&cond=Covid19&draw=2&rank=16 https://trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2021/04/032648 https://trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2021/03/032060 https://trialsearch.who.int/Trial2.aspx?TrialID=NCT04768179 https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20180205038626N7 https://trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2020/09/028088 https://trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2020/08/027503 https://trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2020/07/026791 https://trialsearch.who.int/Trial2.aspx?TrialID=NCT04425863
1779 Harris PA, et al. Discovery of Small Molecule RIP1 Kinase Inhibitors for the Treatment of Pathologies Associated with Necroptosis. ACS Med Chem Lett. 2013 Nov 4;4(12):1238-43.
1780 Biorg Khim 21: 695 (1995)
1781 Helv Chim Acta 17:1407 (1934); J Chem Soc 1940:1390; 1940:1483
1782 Goossens JF, et al. DNA interaction of the tyrosine protein kinase inhibitor PD153035 and its N-methyl analogue. Biochemistry. 2001 Apr 17;40(15):4663-71.
1783 Zheng X, et al. Discovery of Ziresovir as a Potent, Selective, and Orally Bioavailable Respiratory Syncytial Virus Fusion Protein Inhibitor. J Med Chem. 2019 Jul 11;62(13):6003-6014.
1784 Kessler D, et al. Drugging an undruggable pocket on KRAS. Proc Natl Acad Sci U S A. 2019 Aug 6; 116(32):15823-15829.
1785 Dirk Kessler, et al. Drugging all RAS isoforms with one pocket. FUTURE MEDICINAL CHEMISTRY
1786 Tanjoni I, et al. PND-1186 FAK inhibitor selectively promotes tumor cell apoptosis in three-dimensional environments. Cancer Biol Ther. 2010 May 15;9(10):764-77.
1787 Schuller M, et al. Discovery of a Selective Allosteric Inhibitor Targeting Macrodomain 2 of Polyadenosine-Diphosphate-Ribose Polymerase 14. ACS Chem Biol. 2017 Nov 17;12(11):2866-2874.
1788 Gokbulut C, et al. Comparative pharmacokinetics of levamisole-oxyclozanide combination in sheep and goats following per os administration. Can J Vet Res. 2014 Oct;78(4):316-20. |Experientia 1969:883; Br J Pharmac 50:435 (1974)
1789 Vernier JM, et al. 4-[[2-(1-Methyl-2-pyrrolidinyl)ethyl]thio]phenol hydrochloride (SIB-1553A): a novel cognitive enhancer with selectivity for neuronal nicotinic acetylcholine receptors. J Med Chem. 1999 May 20;42(10):1684-6.
1790 Rao TS, et al. In vitro pharmacological characterization of (+/-)-4-[2-(1-methyl-2-pyrrolidinyl)ethyl]thio]phenol hydrochloride (SIB-1553A), a nicotinic acetylcholine receptor ligand. Brain Res. 2003 Aug 15;981(1-2):85-98.
1791 Rao TS, et al. In vivo pharmacological characterization of (+/-)-4-[2-(1-methyl-2-pyrrolidinyl)ethyl]thiophenol hydrochloride (SIB-1553A), a novel cholinergic ligand: microdialysis studies. Brain Res. 2003 Oct 3;986(1-2):71-81.
1792 Mario R. Mautino, et al. Abstract 491: NLG919, a novel indoleamine-2,3-dioxygenase (IDO)-pathway inhibitor drug candidate for cancer therapy. AACR 104th Annual Meeting 2013; Apr 6-10, 2013.
1793 Li M, et al. The indoleamine 2,3-dioxygenase pathway controls complement-dependent enhancement of chemo-radiation therapy against murine glioblastoma. J Immunother Cancer. 2014 Jul 7;2:21.
1794 Chen Y, et al. An immunostimulatory dual-functional nanocarrier that improves cancer immunochemotherapy. Nat Commun. 2016 Nov 7;7:13443.
1795 Life Sci 76:71 (2002); World J Gastroenterol 14:4784 (2008)
1796 J Reprod Med 46:647 (2001); Contraception 16:541 (1977); 32:311 (1985)
1797 https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=PREDNISONE&cntry=&state=&city=&dist=&Search=Search
1798 Masashi Ohmi, et al. Identification of a novel 2-pyridyl-benzensulfonamide derivative, RQ-00203078, as a selective and orally active TRPM8 antagonist. Bioorg Med Chem Lett. 2014 Dec 1;24(23):5364-8.
1799 Yoshihiko Okamoto, et al. Blockade of TRPM8 activity reduces the invasion potential of oral squamous carcinoma cell lines. Int J Oncol. 2012 May;40(5):1431-40.
1800 Katsumata K, et al. Pharmacokinetics and pharmacodynamics of ASP2151, a helicase-primase inhibitor, in a murine model of herpes simplex virus infection. Antimicrob Agents Chemother. 2013 Mar;57(3):1339-46.
1801 Dai XQ, et al. Inhibition of TRPP3 channel by MK-870 and analogs. Mol Pharmacol. 2007 Dec;72(6):1576-85.
1802 Shi H, et al. Na+/H+ Exchanger Regulates Amino Acid-Mediated Autophagy in Intestinal Epithelial Cells. Cell Physiol Biochem. 2017;42(6):2418-2429.
1803 Zhu BY, et al. A new HDAC inhibitor cinnamoylphenazine shows antitumor activity in association with intensive macropinocytosis.
1804 Narita T, et al. Identification of a novel small molecule HIF-1alpha translation inhibitor. Clin Cancer Res. 2009 Oct 1;15(19):6128-6136.
1805 EMILIA C. CALVARESI, et al. SMALL MOLECULE INHIBITORS OF LACTATE DEHYDROGENASE A AS AN ANTICANCER STRATEGY.
1806 Taylor (unpublished)
1807 Anggakusuma, et al. Effects of macelignan isolated from Myristica fragrans Houtt. on UVB-induced matrix metalloproteinase-9 and cyclooxygenase-2 in HaCaT cells. J Dermatol Sci
1808 Jiyoung Yeo, et al. Effects of a multi-herbal extract on type 2 diabetes. Chin Med. 2011 Mar 4;6:10.
1809 Chun-Ai Cui, et al. Macelignan attenuates LPS-induced inflammation and reduces LPS-induced spatial learning impairments in rats. Neurosci Lett. 2008 Dec 19;448(1):110-4.
1810 Li ML, et al. Pharmacological determinants of 9-aminocamptothecin cytotoxicity. Clin Cancer Res. 2001 Jan;7(1):168-74.
1811 de Souza PL, et al. 9-Aminocamptothecin: a topoisomerase I inhibitor with preclinical activity in prostate cancer. Clin Cancer Res. 1997 Feb;3(2):287-94.
1812 Jeha S, et al. Activity of oral and intravenous 9-aminocamptothecin in SCID mice engrafted with human leukemia. Leuk Lymphoma. 1998 Dec;32(1-2):159-64.
1813 https://clinicaltrials.gov/ct2/show/NCT04330300?term=Nitrendipine&cond=COVID-19&draw=2&rank=1
1814 Quanz M, et al. Preclinical Efficacy of the Novel Monocarboxylate Transporter 1 Inhibitor BAY-8002 and Associated Markers of Resistance. Mol Cancer Ther. 2018 Nov;17(11):2285-2296.
1815 Zhang W, et al. UNC2025, a Potent and Orally Bioavailable MER/FLT3 Dual Inhibitor. J Med Chem. 2014 Aug 28;57(16):7031-41.
1816 DeRyckere D, et al. UNC2025, a MERTK Small-Molecule Inhibitor, Is Therapeutically Effective Alone and in Combination with CL14377 in Leukemia Models.Clin Cancer Res. 2017 Mar 15;23(6):1481-1492.
1817 ARVID CARLSSON, et al. 3,4-Dihydroxyphenylalanine and 5-Hydroxytryptophan as Reserpine Antagonists. Nature 180, page1200 (1957).
1818 Caruso I, et al. Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome. J Int Med Res. 1990 May-Jun;18(3):201-9.
1819 Thal LJ, et al. Treatment of myoclonus with L-5-hydroxytryptophan and carbidopa: clinical, electrophysiological, and biochemical observations. Ann Neurol. 1980 Jun;7(6):570-6.
1820 Boiardi A, et al. 5-OH-Tryptophane in migraine: clinical and neurophysiological considerations. J Neurol. 1981;225(1):41-6.
1821 Trouillas P, et al. Improvement of cerebellar ataxia with levorotatory form of 5-hydroxytryptophan. A double-blind study with quantified data processing. Arch Neurol. 1988 Nov;45(11):1217-22.
1822 RBN-2397-Inhibiting PARP7, a Key monoPARP Cancer Dependency
1823 Melissa Vasbinder, et al. RBN-2397: A First-in-Class PARP7 Inhibitor Targeting a Newly Discovered Cancer Vulnerability in Stress-Signaling Pathways.
1824 Farmatsiya (Sofia) 27:1 (1977) [CA 90:23458c (1979)]
1825 Ehmann DE, et al.&#x0D; Avibactam is a covalent, reversible, non-β-lactam β-lactamase inhibitor.&#x0D; Proc Natl Acad Sci U S A. 2012 Jul 17;109(29):11663-8.
1826 Livermore DM, et al.&#x0D; Characterization of β-lactamase and porin mutants of Enterobacteriaceae selected with ceftaroline + avibactam (NXL104).&#x0D; J Antimicrob Chemother. 2012 Jun;67(6):1354-8.
1827 Berkhout J, et al. Pharmacokinetics and penetration of GR20263 and avibactam into epithelial lining fluid in thigh- and lung-infected mice. Antimicrob Agents Chemother. 2015 Apr;59(4):2299-304.
1828 Meijer L, et al. Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5. Eur J Biochem. 1997 Jan 15;243(1-2):527-36.
1829 Bai X, et al. CDK5 promotes renal tubulointerstitial fibrosis in diabetic nephropathy via erk1/2/pparγ pathway. Oncotarget. 2016 Apr 27.
1830 Gary C, et al. Selective antitumor activity of roscovitine in head and neck cancer. Oncotarget. 2016 May 23.
1831 Anal Profiles Drug Subst Excip 23:153 (1994)
1832 Lansing TJ, et al. In vitro biological activity of a novel small-molecule inhibitor of polo-like kinase 1. Mol Cancer Ther. 2007 Feb;6(2):450-9. Epub 2007 Jan 31.
1833 Didier C, et al. Evaluation of Polo-like Kinase 1 inhibition on the G2/M checkpoint in Acute Myelocytic Leukaemia. Eur J Pharmacol. 2008 Sep 4;591(1-3):102-5.
1834 Ikezoe T, et al. A novel treatment strategy targeting polo-like kinase 1 in hematological malignancies. Leukemia. 2009 Sep;23(9):1564-76.
1835 Tamas Oravecz, et al. LX1606 (aka LX1032), a Novel Inhibitor of Serotonin Synthesis, Alleviates Development of Inflammatory Bowel Disease in a Preclinical Model.
1836 Margolis, K.G., et al., Pharmacological reduction of mucosal but not neuronal serotonin opposes inflammation in mouse intestine. Gut, 2013.
1837 Rasmussen SG, et al. Structure of a nanobody-stabilized active state of the β(2) adrenoceptor. Nature. 2011 Jan 13;469(7329):175-80.
1838 https://clinicaltrials.gov/ct2/show/NCT04348305?term=Hydrocortisone&cond=COVID-19&draw=2&rank=1 https://clinicaltrials.gov/ct2/show/NCT04456439?term=Hydrocortisone&cond=COVID-19&draw=2&rank=6 https://clinicaltrials.gov/ct2/show/NCT02735707?term=Hydrocortisone&cond=COVID-19&draw=2&rank=8
1839 Quinlan CL, et al. Targeting S-adenosylmethionine biosynthesis with a novel allosteric inhibitor of Mat2A. Nat Chem Biol. 2017 Jul;13(7):785-792.
1840 Park JH, et al. NecroX-5 prevents breast cancer metastasis by AKT inhibition via reducing intracellular calcium levels. Int J Oncol. 2017 Jan;50(1):185-192.
1841 Thu VT, et al. NecroX-5 exerts anti-inflammatory and anti-fibrotic effects via modulation of the TNFα/Dcn/TGFβ1/Smad2 pathway in hypoxia/reoxygenation-treated rat hearts. Korean J Physiol Pharmacol. 2016 May;20(3):305-14.
1842 Mizutani A, et al. RK-287107, a potent and specific tankyrase inhibitor, blocks colorectal cancer cell growth in a preclinical model. Cancer Sci. 2018 Dec;109(12):4003-4014.
1843 Br J Pharmacol 114:510 (1995)
1844 Crew AP, et al. Identification and Characterization of Von Hippel-Lindau-Recruiting Proteolysis Targeting Chimeras (PROTACs) of TANK-Binding Kinase 1. J Med Chem. 2018 Jan 25;61(2):583-598.
1845 https://trialsearch.who.int/Trial2.aspx?TrialID=DRKS00024520
1846 Fabbro D, et al. PKC412--a protein kinase inhibitor with a broad therapeutic potential. Anticancer Drug Des. 2000 Feb;15(1):17-28.
1847 Gleixner KV, et al. Synergistic growth-inhibitory effects of Midostaurin (PKC412) on neoplastic mast cells carrying KIT D816V. Haematologica. 2013 Sep;98(9):1450-7.
1848 Chi HT, et al. ETV6-NTRK3 as a therapeutic target of small molecule inhibitor PKC412. Biochem Biophys Res Commun. 2012 Dec 7;429(1-2):87-92.
1849 Kwan R, et al. PKC412 normalizes mutation-related keratin filament disruption and hepatic injury in mice by promoting keratin-myosin binding. Hepatology. 2015 Dec;62(6):1858-69.
1850 Fabbro D, et al. Inhibitors of protein kinases: CGP 41251, a protein kinase inhibitor with potential as an anticancer agent. Pharmacol Ther. 1999 May-Jun;82(2-3):293-301.
1851 Infection 5:163 (1977); Arzneim Forsch 29:1915 (1979); J Antimicrob Chemother 11 Suppl B: 1 (1983)
1852 Shevan Silva, Abstract A67: Preclinical efficacy of tarloxotinib bromide (TH-4000), a hypoxia-activated EGFR/HER2 inhibitor: rationale for clinical evaluation in EGFR mutant, T790M-negative NSCLC following progression on EGFR-TKI therapy. Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; November 5-9, 2015; Boston, MA.
1853 Adam V. Patterson, Abstract 5358: The hypoxia-activated EGFR-TKI TH-4000 overcomes erlotinib-resistance in preclinical NSCLC models at plasma levels achieved in a Phase 1 clinical trial. AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA.
1854 Choi S, et al.&#x0D; Activity of Tedizolid Phosphate (TR-701) in Murine Models of Infection with Penicillin-resistant and Penicillin-sensitive Streptococcus pneumoniae.&#x0D; Antimicrob Agents Chemother. 2012 Jun 19.
1855 Moody TW, et al. ML-18 is a non-peptide bombesin receptor subtype-3 antagonist which inhibits lung cancer growth. Peptides. 2015 Feb;64:55-61.
1856 Eidem TM, et al. Drug-eluting cements for hard tissue repair: a comparative study using vancomycin and RNPA1000 to inhibit growth of Staphylococcus aureus. J Biomater Appl. 2014 Apr;28(8):1235-46.
1857 Eidem TM, et al. Small-molecule inhibitors of Staphylococcus aureus RnpA-mediated RNA turnover and tRNA processing. Antimicrob Agents Chemother. 2015 Apr;59(4):2016-28.
1858 Patrick D Olson, et al. Small molecule inhibitors of Staphylococcus aureus RnpA alter cellular mRNA turnover, exhibit antimicrobial activity, and attenuate pathogenesis. PLoS Pathog. 2011 Feb 10;7(2):e1001287.
1859 Liston BW, et al. Perillyl alcohol as a chemopreventive agent in N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis. Cancer Res. 2003 May 15;63(10):2399-403.
1860 Metab: Clin Exper 49:704 (2000); Neurosci 161:501 (2009); J Neurochem 114:291 (2010)
1861 Kenneth W. Duncan et al. Structure and Property Guided Design in the Identification of PRMT5 Tool Compound EPZ015666. ACS Med. Chem. Lett., 2016, 7 (2), pp 162-166.
1862 Chiang K, et al. PRMT5 Is a Critical Regulator of Breast Cancer Stem Cell Function via Histone Methylation and FOXP1 Expression. Cell Rep. 2017 Dec 19;21(12):3498-3513.
1863 https://clinicaltrials.gov/ct2/show/NCT04273581?term=THALIDOMIDE&cond=covid&draw=2&rank=1
1864 1. Griffett K, et al. The mammalian clock and chronopharmacology. Bioorganic &amp; Medicinal Chemistry Letters, 2013, 23(7):1929-1934..
1865 Hirota T, et al. High-throughput chemical screen identifies a novel potent modulator of cellular circadian rhythms and reveals CKIα as a clock regulatory kinase. PLoS Biol. 2010 Dec 14;8(12):e1000559.
1866 Ogunleye A, et al. Fatty acid composition of breast milk from Nigerian and Japanese women. J Nutr Sci Vitaminol (Tokyo). 1991 Aug;37(4):435-42.
1867 Yamori Y, et al. Dietary prevention of stroke and its mechanisms in stroke-prone spontaneously hypertensive rats--preventive effect of dietary fibre and palmitoleic acid. J Hypertens Suppl. 1986 Oct;4(3):S449-52.
1868 Martin LJ, et al. Structure-Based Design of an in Vivo Active Selective BRD9 Inhibitor. J Med Chem. 2016 May 26;59(10):4462-75.
1869 Rezaul M. Karim, et al. An Advanced Tool To Interrogate BRD9. J. Med. Chem., 2016, 59 (10), pp 4459-4461
1870 Briscoe CP, et al. Pharmacological regulation of insulin secretion in MIN6 cells through the fatty acid receptor GPR40: identification of agonist and antagonist small molecules. Br J Pharmacol. 2006 Jul;148(5):619-28.
1871 Zhao YF, et al. Activation of ATP-sensitive potassium channels in rat pancreatic beta-cells by linoleic acid through both intracellular metabolites and membrane receptor signalling pathway. J Endocrinol, 2008, 198(3), 533-540.
1872 Fujita T, et al. A GPR40 agonist GW9508 suppresses CCL5, CCL17, and CXCL10 induction in keratinocytes and attenuates cutaneous immune inflammation. J Invest Dermatol, 2011, 131(8), 1660-1667.
1873 Suski M, et al. Anti-atherosclerotic action of GW9508 - Free fatty acid receptors activator - In apoE-knockout mice. Pharmacol Rep. 2019 Aug;71(4):551-555.
1874 Thomas DR, et al. Functional characterisation of the human cloned 5-HT7 receptor (long form); antagonist profile of SB-258719. Br J Pharmacol. 1998 Jul;124(6):1300-6.
1875 Indian J Chem 6: 252 (1968); J Sci Food Agricult 90:43 (2010)|
1876 Zhai ZJ, et al. Andrographolide suppresses RANKL-induced osteoclastogenesis in vitro and prevents inflammatory bone loss in vivo. Br J Pharmacol. 2014 Feb;171(3):663-75.
1877 Gupta S, et al. Broad-spectrum antiviral properties of andrographolide. Arch Virol. 2017 Mar;162(3):611-623.
1878 Thomson DW, et al. Discovery of GSK8612, a Highly Selective and Potent TBK1 Inhibitor. ACS Med Chem Lett. 2019 Mar 11;10(5):780-785.
1879 Pei Z, et al. Discovery and Biological Profiling of Potent and Selective mTOR Inhibitor GDC-0349. ACS Med Chem Lett. 2012 Nov 29;4(1):103-7.
1880 Koehler MF, et al. Potent, selective, and orally bioavailable inhibitors of the mammalian target of rapamycin kinase domain exhibiting single agent antiproliferative activity. J Med Chem. 2012 Dec 27;55(24):10958-71.
1881 Dong H, et al. Enrichment and separation of antitumor triterpene acids from the epidermis of Poria cocos by pH-zone-refining counter-current chromatography and conventional high-speed counter-current chromatography. J Sep Sci. 2015 Jun;38(11):1977-82.
1882 Chen DQ, et al. Poricoic acid A enhances melatonin inhibition of AKI-to-CKD transition by regulating Gas6/AxlNFκB/Nrf2 axis. Free Radic Biol Med. 2019 Apr;134:484-497.
1883 Phytochemistry 15:572 (1976); African J Traditional, complimentary Med 11(4) (2014)
1884 Sturino CF, et al. Discovery of a potent and selective prostaglandin D2 receptor antagonist, [(3R)-4-(4-chloro-benzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]-acetic acid (MK-0524). J Med Chem. 2007 Feb 22;50(4):794-806.
1885 Philipose S, et al. Laropiprant Attenuates EP3 and TP Prostanoid Receptor-Mediated Thrombus Formation. PLoS One. 2012;7(8):e40222.
1886 https://clinicaltrials.gov/ct2/show/NCT04467931?term=Eplerenone&cond=Covid19&draw=2&rank=1
1887 Norbert Schmees, et al. 3-oxo-2,6-diphenyl-2,3-dihydropyridazine-4-carboxamides. WO2017202816A1.
1888 Kolstoe SE, et al. Molecular dissection of Alzheimer's disease neuropathology by depletion of serum amyloid P component. Proc Natl Acad Sci U S A. 2009 May 5;106(18):7619-23.
1889 Sahota T,et al. Target Mediated Drug Disposition Model of CPHPC in Patients with Systemic Amyloidosis. CPT Pharmacometrics Syst Pharmacol. 2015 Feb;4(2):e15.
1890 Dai Z, et al. Current advance in biological production of malic acid using wild type and metabolic engineered strains. Bioresour Technol. 2018 Jun;258:345-353.
1891 Jonas DA, et al. Safety considerations of DNA in food. Ann Nutr Metab. 2001;45(6):235-54.
1892 Wurtman RJ, et al. Effect of oral CDP-choline on plasma choline and uridine levels in humans. Biochem Pharmacol. 2000 Oct 1;60(7):989-92.
1893 Machado-Vieira R, et, al. New therapeutic targets for mood disorders. ScientificWorldJournal. 2010 Apr 13;10:713-26. |Ber 43:3154 (1910); 45:608 (1912); J Neurochem 1:93 (1956); 64:378 (1995)
1894 Podolin PL, et al. In vitro and in vivo characterization of a novel soluble epoxide hydrolase inhibitor. Prostaglandins Other Lipid Mediat. 2013 Jul-Aug;104-105:25-31.
1895 Phebus LA, Johnson KW, Zgombick JM, Characterization of LY344864 as a pharmacological tool to study 5-HT1F receptors: binding affinities, brainpenetration and activity in the neurogenic dural inflammation model of migraine. Life Sci. 1997;61(21):2117-26.
1896 Jeong HJ, Chenu D, Johnson EE, Sumatriptan inhibits synaptic transmission in the rat midbrain periaqueductal grey. Mol Pain. 2008 Nov 11;4:54.
1897 Cohen ML, Schenck K. 5-Hydroxytryptamine(1F) receptors do not participate in vasoconstriction: lack of vasoconstriction to LY344864, a selective serotonin(1F) receptor agonist in rabbit saphenous vein. J Pharmacol Exp Ther. 1999 Sep;290(3):935-9.
1898 Arzneim Forsch 7:237 (1957); 13:324 (1963)
1899 Yuan Y et al. A small-molecule probe of the histone methyltransferase G9a induces cellular senescence in pancreatic adenocarcinoma. ACS Chem Biol. 2012 Jul 20;7(7):1152-7.
1900 Pescatore, S.L. and C. Lindley, Anagrelide: a novel agent for the treatment of myeloproliferative disorders. Expert Opin Pharmacother, 2000. 1(3): p. 537-46.
1901 Petrides, P.E., Anagrelide: what was new in 2004 and 2005? Semin Thromb Hemost, 2006. 32(4 Pt 2): p. 399-408.
1902 Bai ZT, et al. Inhibition of invasion by N-trans-feruloyloctopamine via AKT, p38MAPK and EMT related signals in hepatocellular carcinoma cells. Bioorg Med Chem Lett. 2017 Feb 15;27(4):989-993.
1903 Aida K, et al. Isoliquiritigenin: a new aldose reductase inhibitor from glycyrrhizae radix. Planta Med. 1990 Jun;56(3):254-8.
1904 Sato Y, et al. Isoliquiritigenin, one of the antispasmodic principles of Glycyrrhiza ularensis roots, acts in the lower part of intestine. Biol Pharm Bull. 2007 Jan;30(1):145-9.
1905 Zhang X. Natural antioxidant-isoliquiritigenin ameliorates contractile dysfunction of hypoxic cardiomyocytes via AMPK signaling pathway. Mediators Inflamm. 2013;2013:390890.
1906 Chen X, et al. Isoliquiritigenin inhibits the growth of multiple myeloma via blocking IL-6 signaling. J Mol Med (Berl). 2012 Nov;90(11):1311-9.
1907 Traboulsi H, et al. The Flavonoid Isoliquiritigenin Reduces Lung Inflammation and Mouse Morbidity during Influenza Virus Infection. Antimicrob Agents Chemother. 2015 Oct;59(10):6317-27.
1908 Wang L, et al. A small molecule modulates Jumonji histone demethylase activity and selectively inhibits cancer growth. Nat Commun, 2013. 4: p. 2035.
1909 Banelli B, et al. Small molecules targeting histone demethylase genes (KDMs) inhibit growth of temozolomide-resistant glioblastoma cells. Oncotarget. 2017 Apr 4.
1910 J Med Chem 41:658 (1998); J Clin Psychiatry 63:763 (2001); Eur J Pharmacol 441:137 (2002)
1911 U.S. Pat. Appl. Publ. (2012), US 20120028924 A1
1912 Fitzpatrick LR, et al. Vidofludimus inhibits colonic interleukin-17 and improves hapten-induced colitis in rats by a unique dual mode of action. J Pharmacol Exp Ther. 2012 Sep;342(3):850-60.
1913 Fitzpatrick LR, et al. 4SC-101, a novel immunosuppressive drug, inhibits IL-17 and attenuates colitis in two murine models of inflammatory bowel disease. Inflamm Bowel Dis. 2010 Oct;16(10):1763-77.
1914 Rajabi M, et al. Antiproliferative activity of kinetin riboside on HCT-15 colon cancer cell line. Nucleosides Nucleotides Nucleic Acids. 2012;31(6):474-81.
1915 Choi BH, et al. Kinetin riboside preferentially induces apoptosis by modulating Bcl-2 family proteins and caspase-3 in cancer cells. Cancer Lett. 2008 Mar 8;261(1):37-45.
1916 https://clinicaltrials.gov/ct2/show/NCT04577378?term=ITRACONAZOLE&cond=covid&draw=2&rank=1
1917 Ahn KS,et al. Decursin: a cytotoxic agent and protein kinase C activator from the root of Angelica gigas. Planta Med. 1996;62(1):7-9.
1918 Li J, et al. Decursin inhibits the growth of HepG2 hepatocellular carcinoma cells via Hippo/YAP signaling pathway. Phytother Res. 2018;32(12):2456-2465.
1919 Kim S, et al. Decursin inhibits tumor growth, migration, and invasion in gastric cancer by down-regulating CXCR7 expression. Am J Cancer Res. 2019;9(9):2007-2018. Published 2019 Sep 1.
1920 Wang Z, et al. Proteolysis Targeting Chimeras for the Selective Degradation of Mcl-1/Bcl-2 Derived from Nonselective Target Binding Ligands. J Med Chem. 2019 Sep 12;62(17):8152-8163.
1921 Bradić I, et al. [Hirschsprung's disease -- therapy and results]. Acta Chir Iugosl. 1975;22(2):183-95.
1922 Chua HC, et al. Kavain, the Major Constituent of the Anxiolytic Kava Extract, Potentiates GABAA Receptors: Functional Characteristics and Molecular Mechanism. PLoS One. 2016 Jun 22;11(6):e0157700.
1923 G. Boonen, et al. In vivo Effects of the Kavapyrones (+)-Dihydromethysticin and (±)-Kavain on Dopamine, 3,4-Dihydroxyphenylacetic Acid, Serotonin and 5-Hydroxyindoleacetic Acid Levels in Striatal and Cortical Brain Regions. Planta Medica 64 (1998) 507-510.
1924 Tang X, et al. Kavain Inhibition of LPS-Induced TNF-α via ERK/LITAF. Toxicol Res (Camb). 2016 Jan 1;5(1):188-196.
1925 Pediatrics 25:27 (1960)
1926 Patel S et al. Discovery of dual leucine zipper kinase (DLK, MAP3K12) inhibitors with activity in neurodegeneration models. J Med Chem. 2015 Jan 8;58(1):401-18.
1927 Kapil A, et al. Leishmanicidal activity of 2-benzoxazolinone from Acanthus illicifolius in vitro. Planta Med. 1994 Apr;60(2):187-8.
1928 Batish DR, et al. 2-Benzoxazolinone (BOA) induced oxidative stress, lipid peroxidation and changes in some antioxidant enzyme activities in mung bean (Phaseolus aureus). Plant Physiology and Biochemistry 44(11-12):819-27
1929 Krawiecka M, et al. Synthesis and biological activity of novel series of 1,3-benzoxazol-2(3H)-one derivatives. Acta Pol Pharm. 2013 Mar-Apr;70(2):245-53.
1930 Miandji AM, et al. Synthesis and biological activities of some 1,3-benzoxazol-2(3H)-one derivatives as anti-quorum sensing agents. Arzneimittelforschung. 2012 Jul;62(7):330-4.
1931 Kanthasamy AG, et al. A novel peptide inhibitor targeted to caspase-3 cleavage site of a proapoptotic kinase protein kinase C delta (PKCdelta) protects against dopaminergic neuronal degeneration in Parkinson's disease models. Free Radic Biol Med. 2006 Nov 15;41(10):1578-89.
1932 Knoblach SM, et al. Caspase inhibitor z-DEVD-fmk attenuates calpain and necrotic cell death in vitro and after traumatic brain injury. J Cereb Blood Flow Metab. 2004 Oct;24(10):1119-32.
1933 Yakovlev AG, et al. Activation of CPP32-like caspases contributes to neuronal apoptosis and neurological dysfunction after traumatic brain injury. J Neurosci. 1997, 17(19), 7415-7424.
1934 Huang MY, et al. Chemotherapeutic agent CPT-11 eliminates peritoneal resident macrophages by inducing apoptosis. Apoptosis. 2016 Feb;21(2):130-42.
1935 Ann NY Acad Sci 881:272 (1999); CNS Drug Reviews 8(:177 (2002)
1936 Gaali S, et al. Rapid, Structure-Based Exploration of Pipecolic Acid Amides as Novel Selective Antagonists of the FK506-Binding Protein 51. J Med Chem. 2016 Mar 24;59(6):2410-22.
1937 Balsevich G, et al. Stress-responsive FKBP51 regulates AKT2-AS160 signaling and metabolic function. Nat Commun. 2017 Nov 23;8(1):1725.
1938 Hartmann J, et al. Pharmacological Inhibition of the Psychiatric Risk Factor FKBP51 Has Anxiolytic Properties. J Neurosci. 2015 Jun 17;35(24):9007-16.
1939 Njoroge FG, et al. Challenges in modern drug discovery: a case study of boceprevir, an HCV protease inhibitor for the treatment of hepatitis C virus infection. Acc Chem Res. 2008 Jan;41(1):50-9.
1940 Yao M, et al. Conditional Inducible Triple-Transgenic Mouse Model for Rapid Real-Time Detection of HCV NS3/4A ProteaseActivity. PLoS One. 2016 Mar 4;11(3):e0150894.
1941 Coilly A, et al. Practical management of boceprevir and immunosuppressive therapy in liver transplant recipients with hepatitis C virus recurrence. Antimicrob Agents Chemother. 2012 Nov;56(11):5728-34.
1942 Berenguer M, et al. New developments in the management of hepatitis C virus infection: focus on boceprevir. Biologics. 2012;6:249-56.
1943 Burton MJ, et al. Telaprevir and boceprevir in african americans with genotype 1 chronic hepatitis C: implications for patients and providers. South Med J. 2012 Aug;105(8):431-6.
1944 J Soc Chem Ind 53: 956 (1934)
1945 Syn Commun 20:2659 (1990)
1946 Malamas MS, et al. Design and synthesis of aryl diphenolic azoles as potent and selective estrogen receptor-beta ligands. J Med Chem. 2004;47(21):5021-5040.
1947 Chaudhary SC, et al. Erb-041, an estrogen receptor-β agonist, inhibits skin photocarcinogenesis in SKH-1 hairless mice by downregulating the WNT signaling pathway. Cancer Prev Res (Phila). 2014;7(2):186-198.
1948 Chan KKL, et al. Estrogen receptor modulators genistein, daidzein and ERB-041 inhibit cell migration, invasion, proliferation and sphere formation via modulation of FAK and PI3K/AKT signaling in ovarian cancer. Cancer Cell Int. 2018;18:65. Published 2018 May 1.
1949 https://clinicaltrials.gov/ct2/show/NCT04623385?term=TESTOSTERONE&cond=covid&draw=2&rank=1
1950 Chem Pharm Bull 43:771 (1995); Tetrahedron 51:1143 (1995); J Pharmacol Exp Therap 309:641 (2004)
1951 Ellen Filvaroff, et al. Methods for treating cancer and the use of biomarkers as a predictor of clinical sensitivity to therapies. WO2017120446A1.
1952 CC-90009
1953 WO 2014102818 A1
1954 Pushkareva MYu, et al. Regulation of sphingosine-activated protein kinases: selectivity of activation by sphingoid basesand inhibition by non-esterified fatty acids. Biochem J. 1993 Sep 15;294 ( Pt 3):699-703.
1955 Khan WA, et al. Protein kinase C and platelet inhibition by D-erythro-Sphingosine: comparison with N,N-dimethylsphingosine and commercial preparation. Biochem Biophys Res Commun. 1990 Oct 30;172(2):683-91.
1956 Pham VT, et al. A concise synthesis of a promising protein kinase C inhibitor: D-erythro-Sphingosine. Arch Pharm Res. 2007 Jan;30(1):22-7.
1957 Cheng P, et al. Protein phosphatase 2A (PP2A) activation promotes axonal growth and recovery in the CNS. J Neurol Sci. 2015 Dec 15;359(1-2):48-56.
1958 Beyer CF, et al. TTI-237: a novel microtubule-active compound with in vivo antitumor activity. Cancer Res. 2008 Apr 1;68(7):2292-300.
1959 Beyer CF, et al. The microtubule-active antitumor compound TTI-237 has both DB01229-like and Leurocristine-like properties. Cancer Chemother Pharmacol. 2009 Sep;64(4):681-9.
1960 Toxicol Appl Pharmacol 18:185 (1971)
1961 FEBS Lett 218:55 (1987)
1962 Ishima T, et al. Potentiation of neurite outgrowth by brexpiprazole, a novel serotonin-dopamine activity modulator: a role for serotonin 5-HT1A and 5-HT2A receptors. Eur Neuropsychopharmacol. 2015 Apr;25(4):505-11.
1963 Yoshimi N, et al. Improvement of dizocilpine-induced social recognition deficits in mice by brexpiprazole, a novel serotonin-dopamine activity modulator. Eur Neuropsychopharmacol. 2015 Mar;25(3):356-64.
1964 Irie H, et al. TAS0728, a covalent-binding, HER2-selective kinase inhibitor shows potent antitumor activity in preclinical models. Mol Cancer Ther. 2019 Feb 20.
1965 Fischer KG, et al. Characterization of a Na(+)-Ca(2+) exchanger in podocytes. Nephrol Dial Transplant. 2002 Oct;17(10):1742-50.
1966 Wang X, et al. Effects of amiloride, benzamil, and alterations in extracellular Na+ on the rat afferent arteriole and its myogenic response. Am J Physiol Renal Physiol. 2008 Jul;295(1):F272-82.
1967 Dai XQ, et al. Inhibition of TRPP3 channel by amiloride and analogs. Mol Pharmacol. 2007 Dec;72(6):1576-85.
1968 Castañeda MS, et al. Benzamil inhibits neuronal and heterologously expressed small conductance Ca2+-activated K+channels. Neuropharmacology. 2019 Nov 1;158:107738.
1969 Teiwes J, et al. Epithelial sodium channel inhibition in cardiovascular disease. A potential role for amiloride. Am J Hypertens. 2007 Jan;20(1):109-17.
1970 Luthi-Carter R, et al. SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis. Proc Natl Acad Sci U S A. 2010 Apr 27;107(17):7927-32.
1971 David M. Taylor, et al. A Brain-Permeable Small Molecule Reduces Neuronal Cholesterol by Inhibiting Activity of Sirtuin 2 Deacetylase. ACS Chem Biol. 2011 Jun 17;6(6):540-6.
1972 Cheon MG, et al. AK-1, a specific SIRT2 inhibitor, induces cell cycle arrest by downregulating Snail in HCT116 human colon carcinoma cells. Cancer Lett. 2015 Jan 28;356(2 Pt B):637-45.
1973 Lee SD, et al. AK-1, a SIRT2 inhibitor, destabilizes HIF-1α and diminishes its transcriptional activity during hypoxia. Cancer Lett. 2016 Apr 1;373(1):138-45.
1974 MAXWELL DR, et al. Relative activity of some inhibitors of mono-amine oxidase in potentiating the action of tryptamine in vitro and in vivo. Br J Pharmacol Chemother. 1961 Dec;17:310-20.
1975 Martin LK, et al. A dose escalation and pharmacodynamic study of Triapine and radiation in patients with locally advanced pancreas cancer. Int J Radiat Oncol Biol Phys. 2012 Nov 15;84(4):e475-81.
1976 Yalowich JC, et al. The anticancer thiosemicarbazones Dp44mT and Triapine lack inhibitory effects as catalytic inhibitors or poisons of DNA topoisomerase IIα. Biochem Pharmacol. 2012 Jul 1;84(1):52-8.
1977 Whitnall M, et al. A class of iron chelators with a wide spectrum of potent antitumor activity that overcomes resistance to chemotherapeutics. Proc Natl Acad Sci U S A. 2006 Oct 3;103(40):14901-6.
1978 Kyani A, et al. Discovery and Mechanistic Elucidation of a Class of Protein Disulfide Isomerase Inhibitors for the Treatment of Glioblastoma. ChemMedChem. 2018 Jan 22;13(2):164-177.
1979 Broberg BV, Glenth?j BY, Dias R, et al. Reversal of cognitive deficits by an ampakine (CX516) and sertindole in two animal models of schizophrenia--sub-chronic and early postnatal PCP treatment in attentional set-shifting. Psychopharmacology (Berl). 2009 Nov;206(4):631-40.
1980 A Carabaza, et al. Stereoselective Inhibition of Inducible Cyclooxygenase by Chiral Nonsteroidal Antiinflammatory Drugs. J Clin Pharmacol. 1996 Jun;36(6):505-12.
1981 B Averbeck, et al. Inflammatory Mediators Do Not Stimulate CGRP Release if Prostaglandin Synthesis Is Blocked by S(+)-flurbiprofen in Isolated Rat Skin. Inflamm Res. 2003 Dec;52(12):519-23.
1982 Lovly CM, et al. Insights into ALK-driven cancers revealed through development of novel ALK tyrosine kinaseinhibitors. Cancer Res. 2011 Jul 15;71(14):4920-31.
1983 https://clinicaltrials.gov/ct2/show/NCT04343963?term=PYRIDOSTIGMINE&cond=Covid19&draw=2&rank=1
1984 JACS 81:2220 (1959); Arzneim Forsch 12:314 (1962)|JACS 81:2220 (1959); Ann Pharmacother27:1183 (1993)
1985 Ou C, et al. Dryocrassin ABBA, a novel active substance for use against amantadine-resistant H5N1 avian influenza virus. Front Microbiol. 2015 Jun 16;6:592.
1986 Zhang B, et al. Molecular Mechanism of the Flavonoid Natural Product Dryocrassin ABBA against Staphylococcus aureus Sortase A. Molecules. 2016 Oct 26;21(11).
1987 Li B, et al. An Inhibitory Effect of Dryocrassin ABBA on Staphylococcus aureus vWbp That Protects Mice From Pneumonia. Front Microbiol. 2019 Jan 23;10:7.
1988 Fu RH, et al. Dryocrassin suppresses immunostimulatory function of dendritic cells and prolongs skin allograft survival. Cell Transplant. 2014;23(4-5):641-56.
1989 Han BR, et al. MAPK inhibitors enhance cell death in pyrogallol-treated human pulmonary fibroblast cells via increasing O&lt;sub&gt;2&lt;/sub&gt;&lt;sup&gt;•-&lt;/sup&gt; levels. Oncol Lett. 2017 Jul;14(1):1179-1185.
1990 https://clinicaltrials.gov/ct2/show/NCT04826588?term=Succinic+acid&cond=Covid19&draw=2&rank=1
1991 Park HH, et al. HS-1371, a novel kinase inhibitor of RIP3-mediated necroptosis. Exp Mol Med. 2018 Sep 20;50(9):125.
1992 Jung Y, et al. Eupatilin, an activator of PPARα, inhibits the development of oxazolone-induced atopic dermatitis symptoms in Balb/c mice. Biochem Biophys Res Commun. 2018 Feb 5;496(2):508-514.
1993 Jung Y, et al. Eupatilin with PPARα agonistic effects inhibits TNFα-induced MMP signaling in HaCaT cells. Biochem Biophys Res Commun. 2017 Nov 4;493(1):220-226.
1994 Du L, et al. Eupatilin prevents H2O2-induced oxidative stress and apoptosis in human retinal pigment epithelial cells. Biomed Pharmacother. 2017 Jan;85:136-140.
1995 Takeuchi CS, et al. Discovery of a novel class of highly potent, selective, ATP-competitive, and orally bioavailable inhibitors of the mammalian target of rapamycin (mTOR). J Med Chem. 2013 Mar 28;56(6):2218-34.
1996 Zhu YR, et al. The anti-cancer activity of the mTORC1/2 dual inhibitor XL388 in preclinical osteosarcoma models. Oncotarget. 2016 Aug 2;7(31):49527-49538.
1997 Naturvissenschaften 43:93 (1956); Anal Profiles Drug Subs 3:513 (1974)
1998 Xu JP, et al. Exploring Modifications of an HIV-1 Capsid Inhibitor: Design, Synthesis, and Mechanism of Action.J Drug Des Res. 2018;5(2). pii: 1070. Epub 2018 Aug 13.
1999 Shi J, et al. Small-molecule inhibition of human immunodeficiency virus type 1 infection by virus capsid destabilization.J Virol. 2011 Jan;85(1):542-9.
2000 Br J Anaesth 52:501 (1980); J Pharmaceut Sci Technol 40:48 (1986)
2001 Hess J, et al. Assessment of the nematocidal activity of metallocenyl analogues of monepantel. Dalton Trans. 2016 Nov 28;45(44):17662-17671
2002 Bahrami F, et al. Monepantel induces autophagy in human ovarian cancer cells through disruption of the mTOR/p70S6K signalling pathway. Am J Cancer Res. 2014 Sep 6;4(5):558-71.
2003 Raza A, et al. Increased expression of ATP binding cassette transporter genes following exposure of Haemonchus contortus larvae to a high concentration of monepantel in vitro. Parasit Vectors. 2016 Sep 29;9(1):522.
2004 Stuchlikova, et al. Monepantel induces hepatic cytochromes p450 in sheep in vitro and in vivo. Chem Biol Interact. 2015 Feb 5;227:63-8. ?
2005 Falconer SB, et al. Zinc Chelation by a Small-Molecule Adjuvant Potentiates Meropenem Activity in Vivo against NDM-1-Producing Klebsiella pneumoniae. ACS Infect Dis. 2015;1(11):533-543.
2006 Wu W, et, al. Millepachine showed novel antitumor effects in cisplatin-resistant human ovarian cancer through inhibiting drug efflux function of ATP-binding cassette transporters. Phytother Res. 2018 Dec; 32(12):2428-2435.
2007 Anticancer Res 29:3825 (2009); Endocrinol 154:968 (2013)
2008 Ilavenil S, et al. Trigonelline protects the cardiocyte from hydrogen peroxide induced apoptosis in H9c2 cells. Asian Pac J Trop Med. 2015 Apr;8(4):263-8.
2009 Joanna Folwarczna, et al. Effects of Trigonelline, an Alkaloid Present in Coffee, on Diabetes-Induced Disorders in the Rat Skeletal System. Nutrients. 2016 Mar; 8(3): 133.
2010 Ozçelik B, et al. Cytotoxicity, antiviral and antimicrobial activities of alkaloids, flavonoids, and phenolic acids. Pharm Biol. 2011 Apr;49(4):396-402.
2011 Tetrahedron 21:1441, 3741 (1965); Chem Pharm Bull 28:708, 717 (1980); Phytochemistry 23:2972 (1984)
2012 Morandi A, et al. GDNF-RET signaling in ER-positive breast cancers is a key determinant of response and resistance to aromatase inhibitors. Cancer Res. 2013 Jun 15;73(12):3783-95
2013 Andreucci E, et al. Targeting the receptor tyrosine kinase RET in combination with aromatase inhibitors in ER positive breast cancer xenografts. Oncotarget. 2016 Sep 2. doi: 10.18632/oncotarget.11826. [Epub ahead of print]
2014 Tsimafeyeu I, et al. Targeting FGFR2 with alofanib (RPT835) shows potent activity in tumour models. Eur J Cancer. 2016 Jul;61:20-8.
2015 Khochenkov DA, et al. Antiangiogenic Activity of Alofanib, an Allosteric Inhibitor of Fibroblast Growth Factor Receptor 2. Bull Exp Biol Med. 2015 Nov;160(1):84-7.
2016 Overgaard, J., et al., A randomized double-blind phase III study of nimorazole as a hypoxic radiosensitizer of primary radiotherapy in supraglottic larynx and pharynx carcinoma. Results of the Danish Head and Neck Cancer Study (DAHANCA) Protocol 5-85. Radiother Oncol, 1998. 46(2): p. 135-46.
2017 Roy, R.B., S.M. Laird, and L. Heasman, Treatment of trichomoniasis in the female. A comparison of metronidazole and nimorazole. Br J Vener Dis, 1975. 51(4): p. 281-4.
2018 Henk, J.M., K. Bishop, and S.F. Shepherd, Treatment of head and neck cancer with CHART and nimorazole: phase II study. Radiother Oncol, 2003. 66(1): p. 65-70.
2019 Peter Wardman, et al. Nitroimidazoles as hypoxic cell radiosensitizers and hypoxia probes: misonidazole, myths and mistakes. Br J Radiol. 2019 Jan;92(1093):20170915.
2020 Zohreh Fakhrieh Kashan, et al. Therapeutic effects of Iranian herbal extracts against Trichomonas vaginalis. Iran Biomed J. 2017 Sep;21(5):285-93.
2021 Liu JR, et al. High-selective HDAC6 inhibitor promotes HDAC6 degradation following autophagy modulation and enhanced antitumor immunity in glioblastoma. Biochem Pharmacol. 2019 May; 163:458-471.
2022 https://clinicaltrials.gov/ct2/show/NCT02735707?term=Ticagrelor&cond=Covid19&draw=2&rank=3
2023 https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=PYRIDOXINE+&cntry=&state=&city=&dist=&Search=Search
2024 T Nagano, et al. Enhancement of salivary secretion and neuropeptide (substance P, alpha-calcitonin gene-related peptide) levels in saliva by chronic anethole trithione treatment. J Pharm Pharmacol. 2001 Dec;53(12):1697-702.
2025 Sheng Huang, et al. Synthesis, Characterization, and In Vivo Evaluation of Desmethyl Anethole Trithione Phosphate Prodrug for Ameliorating Cerebral Ischemia-Reperfusion Injury in Rats. ACS Omega. 2020 Feb 24;5(9):4595-4602.
2026 Y Ukai, et al. Chronic anethole trithione treatment enhances the salivary secretion and increases the muscarinic acetylcholine receptors in the rat submaxillary gland. Arch Int Pharmacodyn Ther. 1984 Oct;271(2):206-12.
2027 JACS 48: 2987 (1926); Int J Immunopharmacol 18:693 (1996); Int J Sports Med 20:258 (1999); Mol Nutr Food Res 54:551 (2010)
2028 Cesar Torres-Luna, et al. Formation of Drug-Participating Catanionic Aggregates for Extended Delivery of Non-Steroidal Anti-Inflammatory Drugs from Contact Lenses. Biomolecules. 2019 Oct 10;9(10):593.
2029 Invest Opthamol Visual Sci 17:1941 (1978); Arch Opthamol 96:1839 (1978); Drugs 23:329 (1982)
2030 Atarashi H, et al. Pharmacokinetics of landiolol hydrochloride, a new ultra-short-acting beta-blocker, in patients with cardiac arrhythmias. Clin Pharmacol Ther. 2000 Aug;68(2):143-50.
2031 Okajima M, et al. Landiolol, an ultra-short-acting β1-blocker, is useful for managing supraventricular tachyarrhythmias in sepsis. World J Crit Care Med. 2015 Aug 4;4(3):251-7.
2032 Bauer MR, et al. 2-Sulfonylpyrimidines: Mild alkylating agents with anticancer activity toward p53-compromised cells. Proc Natl Acad Sci U S A. 2016 Sep 6;113(36):E5271-80.
2033 Synnott NC, et al. Mutant p53 as a therapeutic target for the treatment of triple-negative breast cancer: Preclinical investigation with the anti-p53 drug, PK11007. Cancer Lett. 2018 Feb 1;414:99-106
2034 Ali Y Benkherouf, et al. Hops Compounds Modulatory Effects and 6-prenylnaringenin Dual Mode of Action on GABA AReceptors. Eur J Pharmacol. 2020 Apr 15;873:172962.
2035 Am. Heart J. (1976), 92(5), 661-4; Adv. Drug Res. (1970), 5, 197-253; Circulation (1963), 28, 987-93
2036 Kehrer JP et al. Inhibition of peroxisome-proliferator-activated receptor (PPAR)alpha by MK886. Biochem J. 2001 Jun 15.
2037 Gillard J et al. L-663,536 (MK-886) (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2,2 - dimethylpropanoic acid), a novel, orally active leukotriene biosynthesis inhibitor. Can J Physiol Pharmacol. 1989 May;67(5):456-64.
2038 Mancini JA, et al. 5-Lipoxygenase-activating protein is the target of a novel hybrid of two classes of leukotriene biosynthesis inhibitors. Mol Pharmacol. 1992 Feb;41(2):267-72.
2039 J Am Pharm Sci 34: 78 (1945)
2040 Rao VA, et al. The iron chelator Dp44mT causes DNA damage and selective inhibition of topoisomerase IIalpha in breast cancer cells. Cancer Res. 2009 Feb 1;69(3):948-57.
2041 Lovejoy DB, et al. Antitumor activity of metal-chelating compound Dp44mT is mediated by formation of a redox-active copper complex that accumulates in lysosomes. Cancer Res. 2011 Sep 1;71(17):5871-80.
2042 Thirunarayanan N, et al. Taltirelin is a superagonist at the human thyrotropin-releasing hormone receptor. Front Endocrinol (Lausanne). 2012 Oct 9;3:120.
2043 Hoeflich KP, et al. Intermittent administration of MEK inhibitor GDC-0973 plus PI3K inhibitor GDC-0941 triggers robust apoptosis and tumor growth inhibition. Cancer Res. 2012 Jan 1;72(1):210-9.
2044 Choo EF, et al. PK-PD modeling of combination efficacy effect from administration of the MEK inhibitor GDC-0973 and PI3K inhibitor GDC-0941 in A2058 xenografts. Cancer Chemother Pharmacol. 2013 Jan;71(1):133-43.
2045 Wong H, et al. Bridging the gap between preclinical and clinical studies using pharmacokinetic-pharmacodynamic modeling: an analysis of GDC-0973, a MEK inhibitor. Clin Cancer Res. 2012 Jun 1;18(11):3090-9.
2046 Corazao-Rozas P, et al. Mitochondrial oxidative phosphorylation controls cancer cell's life and death decisions upon exposure to MAPK inhibitors. Oncotarget. 2016 Feb 29. doi: 10.18632/oncotarget.7790.
2047 Dixon SJ, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012;149(5):1060-1072.
2048 Skouta R, Dixon SJ, Wang J, et al. Ferrostatins inhibit oxidative lipid damage and cell death in diverse disease models. J Am Chem Soc. 2014;136(12):4551-4556.
2049 Horwath MC, et al. Antifungal Activity of the Lipophilic Antioxidant Ferrostatin-1. Chembiochem. 2017;18(20):2069-2078.
2050 Liu P, Feng Y, et al. Ferrostatin-1 alleviates lipopolysaccharide-induced acute lung injury via inhibiting ferroptosis. Cell Mol Biol Lett. 2020;25:10. Published 2020 Feb 27.
2051 Melania Guerrero Hue, et al. FP282 FERROPTOSIS-MEDIATED CELL DEATH IS DECREASED BY CURCUMIN IN RENAL DAMAGE ASSOCIATED TO RHABDOMYOLYSIS, Nephrology Dialysis Transplantation, Volume 34, Issue Supplement_1, June 2019, gfz106.FP282.
2052 https://clinicaltrials.gov/ct2/show/NCT04469114?term=Tofacitinib&cond=covid-19&draw=2&rank=4
2053 Prog Clin Biol Res 34:271 (1979); Dev Pharmacol Ther 1:318 (1980); Lancet 1:643 (1982)
2054 Cur Med Res Opinion 5:366 (1978); Br J Clin Pharmacol 14:49 (1982); J Allergy Clin Immunol 103:223 (1999)
2055 Dey J, et al. Voruciclib, a clinical stage oral CDK9 inhibitor, represses MCL-1 and sensitizes high-risk Diffuse Large B-cell Lymphoma to BCL2 inhibition. Sci Rep. 2017 Dec 21;7(1):18007.
2056 Shimada T, et al. Reverse type I binding spectra of human cytochrome P450 1B1 induced by flavonoid, stilbene, pyrene, naphthalene, phenanthrene, and biphenyl derivatives that inhibit catalytic activity: a structure-function relationship study. Chem Res Toxicol. 2009 Jul;22(7):1325-33.
2057 Int J Clin Psychopharmacol 5:147 (1990); Drugs 55:277 (1998)
2058 Gonzalez-Cabrera PJ, et al. Full pharmacological efficacy of a novel S1P1 agonist that does not require S1P-like headgroup interactions. Mol Pharmacol. 2008 Nov;74(5):1308-18.
2059 Blanco R, et al. The S1P1 receptor-selective agonist CYM-5442 protects retinal ganglion cells in endothelin-1 induced retinal ganglion cell loss. Exp Eye Res. 2017 Nov;164:37-45.
2060 Heltweg B, et al. Antitumor activity of a small-molecule inhibitor of human silent information regulator 2 enzymes. Cancer Res. 2006 Apr 15;66(8):4368-77.
2061 Huarui Zhang, et al. Advances in the discovery of exosome inhibitors in cancer. J Enzyme Inhib Med Chem. 2020 Dec;35(1):1322-1330.
2062 Skuza G, et al. Sigma1 receptor antagonists attenuate antidepressant-like effect induced by co-administration of 1,3 di-o-tolylguanidine (DTG) and memantine in the forced swimming test in rats. Pol J Pharmacol. 2003 Nov-Dec;55(6):1149-52.
2063 Cancer Res 42:903 (1982); J Cell Physiol 144:229 (1990)
2064 Stakišaitis D, et al. The Importance of Gender-Related Anticancer Research on Mitochondrial Regulator Sodium Dichloroacetate in Preclinical Studies In Vivo. Cancers (Basel). 2019 Aug 20;11(8). pii: E1210.
2065 Neurosci Lett 91: 194 (1988)
2066 Sullivan I, et al. Next-Generation EGFR Tyrosine Kinase Inhibitors for Treating EGFR-Mutant Lung Cancer beyond First Line. Front Med (Lausanne). 2017 Jan 18;3:76.
2067 Wu SG, et al. Management of acquired resistance to EGFR TKI-targeted therapy in advanced non-small cell lung cancer. Mol Cancer. 2018 Feb 19;17(1):38.
2068 Yang JC, et al. Safety, Efficacy, and Pharmacokinetics of Almonertinib (HS-10296) in Pretreated Patients With EGFR-Mutated Advanced NSCLC: A Multicenter, Open-label, Phase 1 Trial [published online ahead of print, 2020 Sep 9]. J Thorac Oncol. 2020;S1556-0864(20)30714-0.
2069 Welch CJ, et al. Preparation and evaluation of novel stationary phases for improved chromatographic purification of pneumocandin B0. J Chromatogr A. 2006 Jan 6;1101(1-2):204-13.
2070 Leonard WR Jr, et al. Synthesis of the antifungal beta-1,3-glucan synthase inhibitor CANCIDAS (caspofungin acetate) from pneumocandin B0. J Org Chem. 2007 Mar 30;72(7):2335-43.
2071 Maxam AM, et, al. A new method for sequencing DNA. Proc Natl Acad Sci U S A. 1977 Feb;74(2):560-4.
2072 Oh G, et, al. Cytosine modifications exhibit circadian oscillations that are involved in epigenetic diversity and aging. Nat Commun. 2018 Feb 13;9(1):644.
2073 https://clinicaltrials.gov/ct2/show/NCT04467931?term=ISRADIPINE&cond=covid&draw=2&rank=1
2074 Therapie 32:485 (1977); 36:123 (1981); Am J Cardiol 61:1210 (1988)
2075 Reed CW, et al. Discovery of an orally bioavailable and Central Nervous System (CNS) penetrant mGlu7 NegativeAllosteric Modulator (NAM) in vivo tool compound: N-(2-(1H-1,2,4-triazol-1-yl)-5-(trifluoromethoxy)phenyl)-4-(cyclopropylmethoxy)-3-methoxybenzamide (VU6012962). J Med Chem. 2019 Jan 4.
2076 Infusionstherapie (1990), 17(4), 197-203, ; Nature (1967), 213(5073), 308-9, ; Minerva Med. (1963), 54, 2327-31
2077 Chem Rev 12:181 (1933); J Biol Chem 280:34105 (2005)
2078 Zhong K, et al. Effects of renal impairment on the pharmacokinetics of morinidazole: uptake transporter-mediated renal clearanceof the conjugated metabolites. Antimicrob Agents Chemother. 2014 Jul;58(7):4153-61.
2079 Barry GD, et al. Novel agonists and antagonists for human protease activated receptor 2. J Med Chem. 2010 Oct 28;53(20):7428-40.
2080 Suen JY, et al. Modulating human proteinase activated receptor 2 with a novel antagonist (GB88) and agonist (GB110). Br J Pharmacol. 2012 Mar;165(5):1413-23.
2081 PLoS ONE 4:e7472 (2009)
2082 J Pharm Sci 48:212 (1959); Arzneim Forsch 20:548 (1970)
2083 Clin Pharmacol Ther 13:212 (1972); Fundamental Appl Toxicol 9:496 (1987)
2084 Rebecca VW, et al. PPT1 Promotes Tumor Growth and Is the Molecular Target of Chloroquine Derivatives in Cancer. ancer Discov. 2019 Feb;9(2):220-229.
2085 Lee CS, et al. A review of acitretin, a systemic retinoid for the treatment of psoriasis. Expert Opin Pharmacother. 2005 Aug;6(10):1725-34.
2086 Sengör B, et al. Effects of acitretin on spermatogenesis of rats. J Eur Acad Dermatol Venereol. 2006 Jul;20(6):689-92.
2087 Srimuangwong K, et al. Hexahydrocurcumin enhances inhibitory effect of 5-fluorouracil on HT-29 human colon cancer cells. World J Gastroenterol. 2012 May 21;18(19):2383-9.
2088 Li F, et al. In vitro antioxidant and anti-inflammatory activities of 1-dehydro-
2089 -gingerdione, 6-shogaol, 6-dehydroshogaol and hexahydrocurcumin. Food Chem. 2012 Nov 15;135(2):332-7.
2090 Srimuangwong K, et al. Effects of hexahydrocurcumin in combination with 5-fluorouracil on dimethylhydrazine-induced colon cancer in rats. World J Gastroenterol. 2012 Dec 21;18(47):6951-9.
2091 http://www.drugsupdate.com/generic/view/1111
2092 Kastrinsky DB, et al. Reengineered tricyclic anti-cancer agents. Bioorg Med Chem. 2015 Oct 1;23(19):6528-34.
2093 J Neurochem 65: 889 (1995); Neurosci Lett 273: 163 (1999)
2094 Helv Chim Acta 33: 76 (1950)
2095 He M, et al. Pipecolic acid in microbes: biosynthetic routes and enzymes. J Ind Microbiol Biotechnol. 2006 Jun;33(6):401-7.
2096 Plecko B, et, al. Pipecolic acid as a diagnostic marker of pyridoxine-dependent epilepsy. Neuropediatrics. 2005 Jun;36(3):200-5.
2097 Chou TF, et al. Structure-activity relationship study reveals ML240 and ML241 as potent and selective inhibitors of p97 ATPase. ChemMedChem. 2013 Feb;8(2):297-312.
2098 Chou TF, et al. Selective, reversible inhibitors of the AAA ATPase p97. Probe Reports from the NIH Molecular Libraries Program. April 14, 2011.
2099 Takeda O, et al. A comparative study on essential oil components of wild and cultivated Atractylodes lancea and A. chinensis. Planta Med. 1996 Oct;62(5):444-9.
2100 Hai-Ping Chen, et al. Insecticidal and repellant activities of polyacetylenes and lactones derived from Atractylodes lancea rhizomes. Chem Biodivers. 2015 Apr;12(4):593-8.
2101 Heine HS, et al. Activity of dalbavancin against Bacillus anthracis in vitro and in a mouse inhalation anthrax model. Antimicrob Agents Chemother. 2010 Mar;54(3):991-6.
2102 Bennett JW, et al. Dalbavancin in the treatment of complicated skin and soft-tissue infections: a review. Ther Clin Risk Manag. 2008 Feb;4(1):31-40.
2103 Hill, R. J. et al. Pamapimod, a novel p38 mitogen-activated protein kinase inhibitor: preclinical analysis of efficacy and selectivity. The Journal of pharmacology and experimental therapeutics 327, 610-619, doi:10.1124/jpet.108.139006 (2008).
2104 https://clinicaltrials.gov/ct2/show/NCT04405102?term=Ozanimod&cond=covid&draw=2&rank=1
2105 Rzymski T, et al. SEL120-34A is a novel CDK8 inhibitor active in AML cells with high levels of serine phosphorylation of STAT1 and STAT5 transactivation domains. Oncotarget. 2017 May 16;8(20):33779-33795.
2106 J Am Chem Soc 79: 5721 (1957); 88: 3408 (1966); J Org Chem 29: 3727 (1964)|
2107 Khan M, et al. Alantolactone induces apoptosis in HepG2 cells through GSH depletion, inhibition of STAT3 activation, and mitochondrial dysfunction. Biomed Res Int. 2013;2013:719858.
2108 Chun J, et al. Alantolactone selectively suppresses STAT3 activation and exhibits potent anticancer activity in MDA-MB-231 cells. Cancer Lett. 2015 Feb 1;357(1):393-403.
2109 He Q, et al. Inhibition of serine palmitoyltransferase by myriocin, a natural mycotoxin, causes inductionof c-myc in mouse liver. Mycopathologia. 2004 Apr;157(3):339-47.
2110 Amemiya F, et al. Targeting lipid metabolism in the treatment of hepatitis C virus infection. J Infect Dis. 2008 Feb 1;197(3):361-70.
2111 Ciesek S, et al. The suppressive effect that myriocin has on hepatitis C virus RNA replication is independent of inhibition of serine palmitoyl transferase. J Infect Dis. 2008 Oct 1;198(7):1091-3.
2112 Ha HJ, et al. Discovery of an Orally Bioavailable Benzofuran Analogue That Serves as a β-Amyloid Aggregation Inhibitor for the Potential Treatment of Alzheimer's Disease. J Med Chem. 2018 Jan 11;61(1):396-402.
2113 Lobell RB, et al. Preclinical and clinical pharmacodynamic assessment of L-778,123, a dual inhibitor of farnesyl:protein transferase and geranylgeranyl:protein transferase type-I. Mol Cancer Ther. 2002 Jul;1(9):747-758.
2114 Ghasemi S, et al. Comparison of Cytotoxic Activity of L778123 as a Farnesyltranferase Inhibitor and Doxorubicin against A549 and HT-29 Cell Lines. Adv Pharm Bull. 2013;3(1):73-77.
2115 https://clinicaltrials.gov/ct2/results?cond=Covid19&term=MYCOPHENOLIC+ACID&cntry=&state=&city=&dist=
2116 J Pharmacol Exp Ther 275:101 (1995); Clin Neuropharmacol 28:83 (2005)
2117 Furet P, et al. Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation. Bioorg Med Chem Lett. 2013 Jul 1;23(13):3741-8.
2118 Fritsch C, et al. Characterization of the novel and specific PI3Kα inhibitor NVP-BYL719 and development of the patient stratification strategy for clinical trials. Mol Cancer Ther. 2014 May;13(5):1117-29.
2119 Gobin B, et al. BYL719, a new α-specific PI3K inhibitor: single administration and in combination with conventional chemotherapy for the treatment of osteosarcoma. Int J Cancer. 2015 Feb 15;136(4):784-96.
2120 Pauly A, et al. In vitro and in vivo comparative toxicological study of a new preservative-free latanoprost formulation. Invest Ophthalmol Vis Sci. 2012 Dec 13;53(13):8172-80.
2121 Tsai S, et al. The effect of topical latanoprost on anterior segment anatomic relationships in normal dogs. Vet Ophthalmol. 2013 Sep;16(5):370-6.
2122 Zheng J, et al. Latanoprost promotes neurite outgrowth in differentiated RGC-5 cells via the PI3K-Akt-mTOR signaling pathway. Cell Mol Neurobiol. 2011 May;31(4):597-604.
2123 Ooi YH, et al. Effect of bimatoprost, latanoprost, and unoprostone on matrix metalloproteinases and their inhibitors in human ciliary body smooth muscle cells. Invest Ophthalmol Vis Sci. 2009 Nov;50(11):5259-65.
2124 B'Ann True Gabelt, et al. Prostaglandin Subtype-Selective and Non-Selective IOP-Lowering Comparison in Monkeys.
2125 Vidya Balasubramanian, et al. CPI-169, a novel and potent EZH2 inhibitor, synergizes with CHOP in vivoand achieves complete regression in lymphoma xenograft models. Cancer Res October 1, 2014 74; 1697
2126 Bradley WD, et al. EZH2 inhibitor efficacy in non-Hodgkin's lymphoma does not require suppression of H3K27 monomethylation. Chem Biol. 2014 Nov 20;21(11):1463-75
2127 Vitorino P, et al. MAP4K4 regulates integrin-FERM binding to control endothelial cell motility. Nature. 2015 Mar 26;519(7544):425-30.
2128 Noa Shelach. Novel braf inhibitors and use there of for treatment of cutaneous reactions. WO2019026065A2.
2129 Nakahara T, et al. YM155, a novel small-molecule survivin suppressant, induces regression of established human hormone-refractory prostate tumor xenografts. Cancer Res. 2007 Sep 1;67(17):8014-21.
2130 Iisa T, et al. Radiosensitizing effect of YM155, a novel small-molecule survivin suppressant, in non-small cell lung cancer cell lines. Clin Cancer Res. 2008 Oct 15;14(20):6496-504.
2131 Guo K, et al. A combination of YM-155, a small molecule survivin inhibitor, and IL-2 potently suppresses renal cell carcinoma in murine model. Oncotarget. 2015 Aug 28;6(25):21137-47.
2132 Mondal S, et al. Therapeutic targeting of PFKFB3 with a novel glycolytic inhibitor PFK158 promotes lipophagy and chemosensitivity in gynecologic cancers. Int J Cancer. 2019 Jan 1;144(1):178-189.
2133 Zhang Y, et al. Synergistic Effect of Colistin Combined with PFK-158 against Colistin-Resistant Enterobacteriaceae. Antimicrob Agents Chemother. 2019 Jun 24;63(7). pii: e00271-19.
2134 Pooran Chand, et al. Pfkfb3 inhibitor and methods of use as an anti-cancer therapeutic. WO2013148228A1.
2135 Kwon JS, et al. Satisfaction of immediate or delayed switch to paliperidone palmitate in patients unsatisfied with current oral atypical antipsychotics. Int Clin Psychopharmacol. 2015;30(6):320-328.
2136 Q Rev Chem Soc 8:67 (1954)
2137 Arch. Ophthalmol. (1975), 93(10), 1011-4; Proc. Soc. Exp. Biol. Med. (1959), 101, 653-6; Metab., Clin. Exp. (1958), 7, 398-404
2138 https://clinicaltrials.gov/ct2/show/NCT04712357?term=TENOFOVIR&cond=COVID-19&draw=2&rank=1 https://clinicaltrials.gov/ct2/show/NCT04685512?term=TENOFOVIR&cond=COVID-19&draw=2&rank=2 https://clinicaltrials.gov/ct2/show/NCT04519125?term=TENOFOVIR&cond=COVID-19&draw=2&rank=3 https://clinicaltrials.gov/ct2/show/NCT04812496?term=TENOFOVIR&cond=COVID-19&draw=2&rank=4 https://clinicaltrials.gov/ct2/show/NCT04405271?term=TENOFOVIR&cond=COVID-19&draw=2&rank=5 https://clinicaltrials.gov/ct2/show/NCT04334928?term=TENOFOVIR&cond=COVID-19&draw=2&rank=6 https://clinicaltrials.gov/ct2/show/NCT04359095?term=TENOFOVIR&cond=COVID-19&draw=2&rank=7 https://clinicaltrials.gov/ct2/show/NCT04890626?term=TENOFOVIR&cond=COVID-19&draw=2&rank=8 https://clinicaltrials.gov/ct2/show/NCT04575545?term=TENOFOVIR&cond=COVID-19&draw=2&rank=9 https://trialsearch.who.int/Trial2.aspx?TrialID=NCT04712357 https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20200421047155N1
2139 Acta Psychiat Scand 52:237 (1975); Life Sci 80:74 (2006)
2140 https://clinicaltrials.gov/ct2/show/NCT04482595?term=Genistein&cond=COVID-19&draw=2&rank=1
2141 Tardif KD, et al. Characterization of the cellular and antitumor effects of MPI-0479605, a small-molecule inhibitor of the mitotic kinase Mps1. Mol Cancer Ther. 2011 Dec;10(12):2267-2275.
2142 Neuropharmacology (1980), 19(7), 643-52; Am. J. Med. Sci. (1957), 234, 74-7; Ann. Neurol. (1979), 6(5), 410-4
2143 Petersen DN, et al. A Small-Molecule Anti-secretagogue of PCSK9 Targets the 80S Ribosome to Inhibit PCSK9 Protein Translation. Cell Chem Biol. 2016 Nov 17;23(11):1362-1371
2144 Chem Ind 1962:1652; 1964:838, 1691; Naturwissenschaften 50:155 (1963)
2145 Zucconi BE, et al. Modulation of p300/CBP Acetylation of Nucleosomes by Bromodomain LigandI-CBP112. Biochemistry. 2016 Jul 12;55(27):3727-34.
2146 Picaud S, et al. Generation of a Selective Small Molecule Inhibitor of the CBP/p300 Bromodomain for Leukemia Therapy. Cancer Res. 2015 Dec 1;75(23):5106-19.
2147 mixed galloyl esters of penta-o-galloylglucose (m-digalloyl shown)|
2148 Xi Chu, et al. Effects of Tannic Acid, Green Tea and Red Wine on hERG Channels Expressed in HEK293 Cells. PLoS One. 2015; 10(12): e0143797.
2149 Karuppagounder V, et al. Tannic acid modulates NFκB signaling pathway and skin inflammation in NC/Nga mice through PPARγ expression. Cytokine. 2015 Dec;76(2):206-13.
2150 Tojo M, et al. The ALK-5 inhibitor A-83-01 inhibits Smad signaling and epithelial-to-mesenchymal transition by transforming growth factor-beta. Cancer Sci. 2005 Nov;96(11):791-800.
2151 Chem Commun 1974:249; Chem Nat Compounds 38:161 (2002)
2152 Br J Dermatol 111:115 (1984); 114:493 (1986); J Am Acad Dermatol 17:1033 (1987)
2153 Treatment with VX-661 and Ivacaftor in a Phase 2 Study Resulted in Statistically Significant Improvements in Lung Function in People with Cystic Fibrosis Who Have Two Copies of the F508del Mutation. April 18, 2013
2154 Jiang X, et al. Dracorhodin perchlorate regulates fibroblast proliferation to promote rat's wound healing. J Pharmacol Sci. 2018 Feb;136(2):66-72.
2155 He Y, et al. Dracorhodin perchlorate suppresses proliferation and induces apoptosis in human prostate cancer cell line PC-3. J Huazhong Univ Sci Technolog Med Sci. 2011 Apr;31(2):215.
2156 Chen X, et al. Dracorhodin perchlorate induces the apoptosis of glioma cells. Oncol Rep. 2016 Apr;35(4):2364-72.
2157 Mazzanti A, et, al. Hydroquinidine Prevents Life-Threatening Arrhythmic Events in Patients With Short QT Syndrome. J Am Coll Cardiol. 2017 Dec 19;70(24):3010-3015.
2158 Hermida JS, et, al. Hydroquinidine therapy in Brugada syndrome. J Am Coll Cardiol. 2004 May 19;43(10):1853-60.
2159 Chimienti M, et, al. Comparison of the effectiveness of dihydroquinidine and quinidine on ventricular ectopy after acute and chronic administration. Cardiovasc Drugs Ther. 1988 Dec;2(5):679-86. |Arzneim. Forsch. (1977), 27(3), 589-93; Therapie (1971), 26(1), 97-107; Experientia (1971), 27(9), 1100-1.
2160 https://clinicaltrials.gov/ct2/show/NCT04465695?term=Clofazimine&cond=COVID-19&draw=2&rank=1
2161 Vo BN, et al. VU0810464, a non-urea G protein-gated inwardly rectifying K+ (Kir 3/GIRK) channel activator, exhibits enhanced selectivity for neuronal Kir 3 channels and reduces stress-induced hyperthermia in mice.Br J Pharmacol. 2019 Jul;176(13):2238-2249.
2162 Wieting JM,et al. Discovery and Characterization of 1H-Pyrazol-5-yl-2-phenylacetamides as Novel, Non-Urea-Containing GIRK1/2 Potassium Channel Activators.ACS Chem Neurosci. 2017 Sep 20;8(9):1873-1879.
2163 Benaim G, et al. Amiodarone has intrinsic anti-Trypanosoma cruzi activity and acts synergistically with posaconazole. J Med Chem. 2006 Feb 9;49(3):892-9.
2164 Sabatelli F, et al. In vitro activities of posaconazole, fluconazole, itraconazole, voriconazole, and amphotericin B against a large collection of clinically important molds and yeasts. Antimicrob Agents Chemother. 2006 Jun;50(6):2009-15.
2165 Sansone-Parsons A, et al. Effect of a nutritional supplement on posaconazole pharmacokinetics following oral administration to healthy volunteers. Antimicrob Agents Chemother. 2006 May;50(5):1881-3.
2166 Veiga-Santos P, et al. Effects of amiodarone and posaconazole on the growth and ultrastructure of Trypanosoma cruzi. Int J Antimicrob Agents. 2012 Jul;40(1):61-71.
2167 Sun QN, et al. In vivo activity of posaconazole against Mucor spp. in an immunosuppressed-mouse model. Antimicrob Agents Chemother. 2002 Jul;46(7):2310-2.
2168 Williams H, et al. Fluralaner, a novel isoxazoline, prevents flea (Ctenocephalides felis) reproduction in vitro and in asimulated home environment. Parasit Vectors. 2014 Jun 19;7:275.
2169 Walther FM, et al. Safety of fluralaner, a novel systemic antiparasitic drug, in MDR1(-/-) Collies after oral administration. Parasit Vectors. 2014 Mar 6;7:86.
2170 Matthew C. Stubbs, et al. Abstract 5071: Preclinical characterization of the potent and selective BET inhibitor INCB057643 in models of hematologic malignancies. AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5071.
2171 Smith AL, et al. Discovery of 1H-pyrazol-3(2H)-ones as potent and selective inhibitors of protein kinase R-like endoplasmic reticulum kinase (PERK). J Med Chem. 2015 Feb 12;58(3):1426-41.
2172 Roest G, et al. The ER Stress Inducer l-Azetidine-2-Carboxylic Acid Elevates the Levels of Phospho-eIF2α and of LC3-II in a Ca2+-Dependent Manner. Cells. 2018 Nov 30;7(12). pii: E239.
2173 Sotgiu G et al. Delamanid (OPC-67683) for treatment of multi-drug-resistant tuberculosis. Expert Rev Anti Infect Ther. 2015 Mar;13(3):305-15.
2174 Xavier AS et al. Delamanid: A new armor in combating drug-resistant tuberculosis. J Pharmacol Pharmacother. 2014 Jul;5(3):222-4
2175 Mallikaarjun S et al. Delamanid Coadministered with Antiretroviral Drugs or Antituberculosis Drugs Shows No Clinically Relevant Drug-Drug Interactions in Healthy Subjects. Antimicrob Agents Chemother. 2016 Sep 23;60(10):5976-85.
2176 Patterson S et al.The anti-tubercular drug delamanid as a potential oral treatment for visceral leishmaniasis. Elife. 2016 May 24;5.
2177 Nguyen GH, et al. A small molecule inhibitor of the BLM helicase modulates chromosome stability in human cells. Chem Biol. 2013 Jan 24;20(1):55-62.
2178 Banerjee T, et al. A new development in DNA repair modulation: discovery of a BLM helicase inhibitor. Cell Cycle. 2013 Mar 1;12(5):713-4.
2179 J Am Chem Soc 76: 4245 (1954); Alkaloids 19: 81 (1981)
2180 J L Stigliani, et al. New Insights Into the Chemical Behavior of S-oxide Derivatives of Thiocarbonyl-Containing Antitubercular Drugs and the Influence on Their Mechanisms of Action and Toxicity. Ann Pharm Fr. 2019 Mar;77(2):126-135.
2181 P Khanna, et al. Characteristics of a Cytosolic Arylacylamidase Metabolizing Thiacetazone. J Pharmacol Exp Ther. 1992 Sep;262(3):1225-31.
2182 Anuradha Alahari, et al. Thiacetazone, an Antitubercular Drug That Inhibits Cyclopropanation of Cell Wall Mycolic Acids in Mycobacteria. PLoS One. 2007 Dec 19;2(12):e1343.
2183 C A Peloquin, et al. Pharmacokinetic Evaluation of Thiacetazone. Pharmacotherapy. Sep-Oct 1996;16(5):735-41.
2184 Agents Actions Suppl. (1986), AAS 19, 169-75; Clin. Pharmacokinet. (1995), 28(3), 216-34; Arzneim. Forsch. (1956), 6, 124-7
2185 Hanan EJ, et al. Design and synthesis of 2-amino-isoxazolopyridines as Polo-like kinase inhibitors. Bioorg Med Chem Lett. 2008 Oct 1;18(19):5186-9.
2186 Stephan Reinhard Künzel, et al. Hypoxia-induced epigenetic silencing of polo-like kinase 2 promotes fibrosis in atrial fibrillation. bioRxiv 445098
2187 Huang CY. Inhibition of a Putative Dihydropyrimidinase from Pseudomonas aeruginosa PAO1 by Flavonoids and Substrates of Cyclic Amidohydrolases. PLoS One. 2015 May 19;10(5):e0127634.
2188 Kou X, et al. Ampelopsin attenuates brain aging of D-gal-induced rats through miR-34a-mediated SIRT1/mTORsignal pathway. Oncotarget. 2016 Nov 15;7(46):74484-74495.
2189 Chang H, et al. Ampelopsin suppresses breast carcinogenesis by inhibiting the mTOR signalling pathway. Carcinogenesis. 2014 Aug;35(8):1847-54.
2190 Václav Zima, et al. Unraveling the Anti-Influenza Effect of Flavonoids: Experimental Validation of Luteolin and its Congeners as Potent Influenza Endonuclease Inhibitors. Eur J Med Chem. 22 August 2020, 112754.
2191 Minke E. Binnerts, et al. Abstract C186: SNS-062 is a potent noncovalent BTK inhibitor with comparable activity against wild type BTK and BTK with an acquired resistance mutation. Molecular Cancer Therapeutics. December 2015 Volume 14, Issue 12 Supplement 2
2192 Catherine A. Fabian, et al. Abstract 1207: SNS-062 demonstrates efficacy in chronic lymphocytic leukemia in vitro and inhibits C481S mutated Bruton tyrosine kinase. Cancer Research July 2017 Volume 77, Issue 13 Supplement
2193 Chan MC, et al. Potent and Selective Triazole-Based Inhibitors of the Hypoxia-Inducible Factor Prolyl-Hydroxylases with Activity in the Murine Brain. PLoS One. 2015 Jul 6;10(7):e0132004.
2194 Lim D, et al. Discovery of a Small-Molecule Inhibitor of Protein-MicroRNA Interaction Using Binding Assay with a Site-Specifically Labeled Lin28. J Am Chem Soc. 2016 Oct 7.
2195 Grootendorst DC, et al. Efficacy of the novel phosphodiesterase-4 inhibitor BAY 19-8004 on lung function and airway inflammation in asthma and chronic obstructive pulmonary disease (COPD). Pulm Pharmacol Ther. 2003;16(6):341-7.
2196 Peter Norman. PDE4 inhibitors: sustained patenting activity as leading drugs near the market. Exp. Opin. Ther. Patents (2000) 10(9):1415-1427.
2197 Effect of substitution of plasticizer dibutyl phthalate with dibutyl sebacate on Eudragit® RS30D drug release rate control.
2198 Disease Models Mech 6 (2013) doi:10.1242/dmm.; 08243
2199 Alexandros Ikonomidis, et al. In vitro and in vivo evaluations of oxacillin efficiency against mecA-positive oxacillin-susceptible Staphylococcus aureus. Antimicrob Agents Chemother. 2008 Nov;52(11):3905-8.
2200 R H Raynor, et al. Oxacillin-induced lysis of Staphylococcus aureus. Antimicrob Agents Chemother. 1979 Aug;16(2):134-40.
2201 https://clinicaltrials.gov/ct2/show/NCT04467931?term=Azilsartan&cond=Covid19&draw=2&rank=1
2202 Clin Appl Thromb Hemost 8:169 (2002)
2203 J. Am. Chem. Soc. (1956), 78, 4498-9; Scand. J. Gastroenterol. (1984), 19(6), 820-3; Experientia (1968), 24(8), 791-2
2204 Lorna Kategaya , et al. USP7 Small-Molecule Inhibitors Interfere With Ubiquitin Binding. Nature. 2017 Oct 26;550(7677):534-538.
2205 Galkin AV, et al. Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK. Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):270-5.
2206 Katayama R, et al. Therapeutic strategies to overcome PF-02341066 resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK. Proc Natl Acad Sci U S A. 2011 May 3;108(18):7535-40.
2207 Schonherr C, Activating ALK mutations found in neuroblastoma are inhibited by PF-02341066 and NVP-TAE684. Biochem J. 2011 Dec 15;440(3):405-13.
2208 Foulks JM, et al. A small-molecule inhibitor of PIM kinases as a potential treatment for urothelial carcinomas. Neoplasia. 2014 May;16(5):403-12.
2209 Teng X, et al. Structure-activity relationship study of [1,2,3]thiadiazole necroptosis inhibitors. Bioorg Med Chem Lett. 2007 Dec 15;17(24):6836-40.
2210 Jagtap PG, et al. Structure-activity relationship study of tricyclic necroptosis inhibitors. J Med Chem. 2007 Apr 19;50(8):1886-95.
2211 Teng X, et al. Structure-activity relationship study of novel necroptosis inhibitors. Bioorg Med Chem Lett. 2005 Nov 15;15(22):5039-44.
2212 Takahashi N, et al. Necrostatin-1 analogues: critical issues on the specificity, activity and in vivo use in experimental disease models. Cell Death Dis. 2012 Nov 29;3:e437.
2213 Newton R, et al. The discovery of 2-substituted phenol quinazolines as potent RET kinase inhibitors with improved KDR selectivity. Eur J Med Chem. 2016 Apr 13;112:20-32.
2214 Ghosh S, et al. 4-[3-Bromo-4-hydroxyphenyl)amino]-6,7-dimethoxyquinazolin-1-ium chloride methanol solvateand 4-[(3-hydroxyphenyl)amino]-6,7-dimethoxy-1-quinazolinium chloride. Acta Crystallogr C. 2001 Jan;57(Pt 1):76-8.
2215 Chen CL, et al. Pharmacokinetics and biologic activity of the novel mast cell inhibitor, 4-(3-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline in mice. Pharm Res. 1999 Jan;16(1):117-22.
2216 Helv Chim Acta 24:297 (1941)
2217 van Wyk JA, et al. Two field strains of Haemonchus contortus resistant to rafoxanide. Onderstepoort J Vet Res. 1987 Jun;54(2):143-6.
2218 Prichard RK, et al. The metabolic profile of adult Fasciola hepatica obtained from rafoxanide-treated sheep. Parasitology. 1978 Jun;76(3):277-88.
2219 Cornish RA, et al. The in vivo effects of rafoxanide on the energy metabolism of Fasciola hepatica. Int J Parasitol. 1977 Jun;7(3):217-20.
2220 Rafoxanide
2221 Zhou B, et al. Discovery of a Small-Molecule Degrader of Bromodomain and Extra-Terminal (BET) Proteins with Picomolar Cellular Potencies and Capable of Achieving Tumor Regression. J Med Chem. 2018 Jan 25;61(2):462-481.
2222 https://clinicaltrials.gov/ct2/show/NCT04979923?term=LIDOCAINE&cond=COVID-19&draw=2&rank=1 https://clinicaltrials.gov/ct2/show/NCT04609865?term=LIDOCAINE&cond=COVID-19&draw=2&rank=2 https://clinicaltrials.gov/ct2/show/NCT04885777?term=LIDOCAINE&cond=COVID-19&draw=2&rank=6 https://trialsearch.who.int/Trial2.aspx?TrialID=NCT04609865
2223 Tierarztl. Praxis (1991), 19(1), 14-20; Antimicrob. Agents Chemother. (1990), 34(3), 496-7; VMR, Vet. Med. Rev. (1987), (2), 90-9
2224 IARC Monographs 10:85 (1976); Anal Profiles Drug Subs 4:47 (1975); 15:701 (1986)
2225 Fundam Appl Toxicol 4:674 (1984); Food Chem Toxicol 23:419 (1985)
2226 Bin Ma, Tonika Bohnert, et al. Discovery of BIIB068: A Selective, Potent, Reversible Bruton's Tyrosine Kinase Inhibitor as an Orally Efficacious Agent for Autoimmune Diseases. J Med Chem. 2020 Jul 22.
2227 J Agric Food Chem 54:2951 (2006); Am J Epidem 166: 924 (2007); Br J Pharmacol 2 155:244 (2008); Neuropharmacol 58: 911 (2010)
2228 Maes MB, et al. In vivo effects of a potent, selective DPPII inhibitor: UAMC00039 is a possible tool for the elucidation of the physiological function of DPPII. Adv Exp Med Biol. 2006;575:73-85.
2229 Maes MB, et al. Dipeptidyl peptidase II and leukocyte cell death. Biochem Pharmacol. 2006 Jun 28;72(1):70-9.
2230 https://clinicaltrials.gov/ct2/show/NCT04394416?term=Imatinib+Mesylate&cond=covid&draw=2&rank=2
2231 Xu MJ, et al. Inhibitory Effects of Danshen components on CYP2C8 and CYP2J2. Chem Biol Interact. 2018 Jun 1;289:15-22.
2232 Song J, et al. Activation of Nrf2 signaling by salvianolic acid C attenuates NF‑κB mediated inflammatory response both in vivo and in vitro. Int Immunopharmacol. 2018 Oct;63:299-310.
2233 Royer JF, et al. A novel antagonist of prostaglandin D2 blocks the locomotion of eosinophils and basophils. Eur J Clin Invest. 2008 Sep;38(9):663-71.
2234 Luker T, et al. Substituted indole-1-acetic acids as potent and selective CRTh2 antagonists-discovery of AZD1981. Bioorg Med Chem Lett. 2011 Nov 1;21(21):6288-92.
2235 Snell N, et al. Efficacy and safety of AZD1981, a CRTH2 receptor antagonist, in patients with moderate to severe COPD. Respir Med. 2013 Nov;107(11):1722-30.
2236 Guo W, et al. Effect of Leonurus stachydrine on myocardial cell hypertrophy. Zhong Yao Cai. 2012 Jun;35(6):940-3.
2237 Yin J, et al. Stachydrine, a major constituent of the Chinese herb leonurus heterophyllus sweet, ameliorates human umbilical vein endothelial cells injury induced by anoxia-reoxygenation. Am J Chin Med. 2010;38(1):157-71.
2238 Rathee P, et al. In vitro anticancer activity of stachydrine isolated from Capparis decidua on prostate cancer cell lines. Nat Prod Res. 2012;26(18):1737-40.
2239 Zhang C, et al. Effects of stachydrine on norepinephrine-induced neonatal rat cardiac myocytes hypertrophy and intracellular calcium transients. BMC Complement Altern Med. 2014 Dec 8;14:474.
2240 Zhang C, et al. Effect of stachydrine on endoplasmic reticulum stress-induced apoptosis in rat kidney after unilateral ureteral obstruction. J Asian Nat Prod Res. 2013;15(4):373-81.
2241 J Nat Prod 47: 901 (1984)
2242 Br J Haematol 132:615 (2006); Planta Med 76:133 (2010)
2243 Res. Vet. Sci. (2004), 76(2), 95-108; Br. Vet. J. (1979), 135(4), 318-23; Am. J. Vet. Res. (1978), 39(6), 1037-8
2244 Nathanael S. Gray, et al. Degraders of wee1 kinase. WO2020069105A1.
2245 Reuberson J, et al. Discovery of a Potent, Orally Bioavailable PI4KIIIβ Inhibitor (UCB9608) Able To Significantly Prolong Allogeneic Organ Engraftment in Vivo. J Med Chem. 2018 Aug 9;61(15):6705-6723.
2246 J Chem Soc 1966:772; Magn Reson Chem 31: 340 (1993)
2247 Ann Intern Med 84:712 (1976); Med Clin North Am 66:169 (1982)
2248 Anticancer Drugs 2001:807; Biochem Pharmacol 67:523 (2004)
2249 Cancer Lett 168:125 (2001); Carcinogenesis 19:1697 (1998)
2250 Chen Y, et al. Discovery of benzenesulfonamide derivatives as potent PI3K/mTOR dual inhibitors with in vivo efficacies against hepatocellular carcinoma. Bioorg Med Chem. 2016 Mar 1;24(5):957-66.
2251 Benjamin R Bellenie, et al. Achieving In Vivo Target Depletion through the Discovery and Optimization of Benzimidazolone BCL6 Degraders. J Med Chem. 2020 Apr 23;63(8):4047-4068.
2252 Acta Diabetologica 31:236 (1994); PNAS 91 9253 (1994)
2253 Sun W, et al. Oroxin A from Oroxylum indicum prevents the progression from prediabetes to diabetes in streptozotocin and high-fat diet induced mice. Phytomedicine. 2018 Jan 1;38:24-34.
2254 He J, et al. Oroxin A inhibits breast cancer cell growth by inducing robust endoplasmic reticulum stress and senescence. Anticancer Drugs. 2016 Mar;27(3):204-15.
2255 Maxson JE, et al. Identification and Characterization of Tyrosine Kinase Nonreceptor 2 Mutations in Leukemia through Integration of Kinase Inhibitor Screening and Genomic Analysis.
2256 Matsuo Y, et al. TOPK inhibitor induces complete tumor regression in xenograft models of human cancer through inhibition ofcytokinesis. Sci Transl Med. 2014 Oct 22;6(259):259ra145.
2257 Lin A, et al. Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials. Sci Transl Med. 2019 Sep 11;11(509).
2258 Lu H, et al. TOPK inhibits autophagy by phosphorylating ULK1 and promotes glioma resistance to TMZ. Cell Death Dis. 2019 Aug 5;10(8):583.
2259 Med Chem Res 19:498 (2010)
2260 Br J Pharmacol 118:915 (1996); 122:1061 (1997); Eur J Pharmacol 361:191 (1998)
2261 Mondal D, et al. Nelfinavir suppresses signaling and nitric oxide production by human aortic endothelial cells: protective effects of thiazolidinediones. Ochsner J. 2013 Spring;13(1):76-90.
2262 Kaldor SW, et al. Nelfinavir mesylate (AG1343): a potent, orally bioavailable inhibitor of HIV-1 protease. J Med Chem. 1997 Nov 21;40(24):3979-85.
2263 Gills JJ, et al. Nelfinavir, A lead HIV protease inhibitor, is a broad-spectrum, anticancer agent that inducesendoplasmic reticulum stress, autophagy, and apoptosis in vitro and in vivo. Clin Cancer Res. 2007 Sep 1;13(17):5183-94.
2264 Bono C, et al. The human immunodeficiency virus-1 protease inhibitor nelfinavir impairs proteasome activity and inhibits the proliferation of multiple myeloma cells in vitro and in vivo. Haematologica. 2012;97(7):1101‐1109.
2265 Sheng, L., H. Chen, and Y. Li, A HPLC method for determination of nicousamide in dog plasma and its application to pharmacokinetic studies. J Chromatogr B Analyt Technol Biomed Life Sci, 2007. 854(1-2): p. 99-103.
2266 Daniel T. Monaghan, et al. Positive and negative modulators of nmda receptors. WO 2012019106 A2.
2267 Van Goor F, et al. Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809. Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):18843-8.
2268 Phuan PW, et al. Synergy-based small-molecule screen using a human lung epithelial cell line yields ΔF508-CFTR correctors that augment VX-809 maximal efficacy. Mol Pharmacol. 2014 Jul;86(1):42-51.
2269 Yang M, et al. PET imaging of early response to the tyrosine kinase inhibitor ZD4190. Eur J Nucl Med Mol Imaging. 2011 Jul;38(7):1237-47. doi: 10.1007/s00259-011-1742-z. Epub 2011 Mar 1.
2270 Gaballah K, et al. The antiangiogenic agent ZD4190 prevents tumour outgrowth in a model of minimal residual carcinoma in deep tissues. Br J Cancer. 2009 Aug 4;101(3):418-23. doi: 10.1038/sj.bjc.6605092. Epub 2009 Jul 21.
2271 Checkley D, et al. Dynamic contrast-enhanced MRI of vascular changes induced by the VEGF-signalling inhibitor ZD4190 in human tumour xenografts. Magn Reson Imaging. 2003 Jun;21(5):475-82.
2272 Cywin CL, et al. Discovery of potent and selective PKC-theta inhibitors. Bioorg Med Chem Lett. 2007 Jan 1;17(1):225-30.
2273 Stephan Siegel, et al. 2,3-benzodiazepines. WO2014026997A1.
2274 Salgado VL, et al. Metaflumizone is a novel sodium channel blocker insecticide. Vet Parasitol. 2007 Dec 15;150(3):182-9. Epub 2007 Oct 23.
2275 Reger TS, et al. Pyridyl amides as potent inhibitors of T-type calcium channels. Bioorg Med Chem Lett. 2011 Mar 15;21(6):1692-6.
2276 Matthaei J, et al. OCT1 Deficiency Affects Hepatocellular Concentrations and Pharmacokinetics of Cycloguanil, the Active Metabolite of the Antimalarial Drug Proguanil. Clin Pharmacol Ther. 2019 Jan;105(1):190-200.
2277 Phytochemistry 16: 9 (1977)
2278 Tvrdeic A, et al. Dihydrogenated ergot compounds bind with high affinity to GABAA receptor-associated Cl- ionophore. Eur J Pharmacol. 1991 Sep 4;202(1):109-11.
2279 Tvrdeic A, et al. Dihydroergotoxine modulation of the GABAA receptor-associated Cl- ionophore in mouse brain. Eur J Pharmacol. 1992 Oct 6;221(1):139-43.
2280 Tvrdeic A, et al. Effect of ergot alkaloids on 3H-flunitrazepam binding to mouse brain GABAA receptors. Coll Antropol. 2003;27 Suppl 1:175-82.
2281 Abdul M, et al. Expression of gamma-aminobutyric acid receptor (subtype A) in prostate cancer. Acta Oncol. 2008;47(8):1546-50.
2282 Eltze T, et al. Imidazoquinolinone, imidazopyridine, and isoquinolindione derivatives as novel and potent inhibitors of the poly(ADP-ribose) polymerase (PARP): a comparison with standard PARP inhibitors. Mol Pharmacol. 2008 Dec;74(6):1587-98.
2283 Arzneim Forsch 31:309 (1981)
2284 Te Du, et al. Vincamine as a GPR40 agonist improves glucose homeostasis in type 2 diabetic mice. J Endocrinol. 2019 Feb 1;240(2):195-214.
2285 Li Wu, et al. Vincamine prevents lipopolysaccharide induced inflammation and oxidative stress via thioredoxin reductase activation in human corneal epithelial cells. Am J Transl Res. 2018 Jul 15;10(7):2195-2204. eCollection |Br J Clin Pharmacol 9:100 (1980); N Engl J Med 305:1562 (1981)
2286 Oku, Y., et al., [Fungicidal activity of liranaftate against Trichophyton rubrum]. Nihon Ishinkin Gakkai Zasshi, 2002. 43(3): p. 181-7.
2287 Oku, Y., N. Takahashi, and K. Yokoyama, [Fungicidal activity of liranaftate against dermatophytes]. Nihon Ishinkin Gakkai Zasshi, 2009. 50(1): p. 9-13.
2288 Maruyama N, et, al. [Suppression of experimental inflammation by anti-fungal agent liranaftate in mice]. Nihon Ishinkin Gakkai Zasshi. 2010;51(1):7-11.
2289 Kobayashi M, et, al. [Anti-fungal drug liranaftate suppresses fungal element-promoted production of IL-8 in normal human keratinocytes]. Nihon Ishinkin Gakkai Zasshi. 2008;49(4):319-22.
2290 Hazel P, et al. Inhibitor Selectivity for Cyclin-Dependent Kinase 7: A Structural, Thermodynamic, and Modelling Study. ChemMedChem. 2017 Mar 7;12(5):372-380.
2291 Patel H, et al. ICEC0942, an Orally Bioavailable Selective Inhibitor of CDK7 for Cancer Treatment. Mol Cancer Ther. 2018 Jun;17(6):1156-1166.
2292 https://clinicaltrials.gov/ct2/show/NCT04885530?term=Fluticasone&cond=covid&draw=2&rank=2
2293 Wengner AM, et al. Novel Mps1 Kinase Inhibitors with Potent Antitumor Activity. Mol Cancer Ther. 2016 Apr;15(4):583-92.
2294 Ackermann TF, et al. EMD638683, a novel SGK inhibitor with antihypertensive potency. Cell Physiol Biochem. 2011;28(1):137-46.
2295 Chem Ind 1954:1320; Int J Biol Med Res 3:1242 (2012)
2296 Jia YS, et al. Antitumor Activity of Tenacissoside H on Esophageal Cancer through Arresting Cell Cycle and Regulating PI3K/Akt-NF-κB Transduction Cascade. Evid Based Complement Alternat Med. 2015;2015:464937.
2297 John A Butera, et al. Discovery of (2S,4R)-1-(2-aminoacetyl)-4-benzamidopyrrolidine-2-carboxylic acid hydrochloride (GAP-134)13, an orally active small molecule gap-junction modifier for the treatment of atrial fibrillation. J Med Chem. 2009 Feb 26;52(4):908-11.
2298 Elke De Vuyst, et al. Pharmacological modulation of connexin-formed channels in cardiac pathophysiology. Br J Pharmacol. 2011 Jun;163(3):469-83.
2299 Witte HM, et al. Trofosfamide in the treatment of elderly or frail patients with diffuse large B-cell lymphoma. J Cancer Res Clin Oncol. 2019 Jan;145(1):129-136.
2300 Görn M, et al. A pilot study of docetaxel and trofosfamide as second-line 'metronomic' chemotherapy in the treatment of metastatic non-small cell lung cancer (NSCLC). Onkologie. 2008 Apr;31(4):185-9.
2301 Fryer, A.D. and J. Maclagan, Ipratropium bromide potentiates bronchoconstriction induced by vagal nerve stimulation in the guinea-pig. Eur J Pharmacol, 1987. 139(2): p. 187-91.
2302 Harvey, K.L., A. Hussain, and H.L. Maddock, Ipratropium Bromide-Mediated Myocardial Injury in In Vitro Models of Myocardial Ischaemia/Reperfusion. Toxicol Sci, 2014.
2303 Maria Prat, et al. Discovery of novel quaternary ammonium derivatives of (3R)-quinuclidinyl amides as potent and long acting muscarinic antagonists. Bioorg Med Chem Lett. 2015 Apr 15;25(8):1736-1741.
2304 Wenhui Zhang, et al. Anti-inflammatory effects of formoterol and ipratropium bromide against acute cadmium-induced pulmonary inflammation in rats. Eur J Pharmacol. 2010 Feb 25;628(1-3):171-8.
2305 Ligresti A, et al. Kavalactones and the endocannabinoid system: the plant-derived yangonin is a novel CB&lt;sub&gt;1&lt;/sub&gt; receptor ligand. Pharmacol Res. 2012 Aug;66(2):163-9.
2306 Ma J, et al. Yangonin blocks tumor necrosis factor-α-induced nuclear factor-κB-dependent transcription by inhibiting the transactivation potential of the RelA/p65 subunit. J Pharmacol Sci. 2012;118(4):447-54.
2307 Wruck CJ, et al. Kavalactones protect neural cells against amyloid beta peptide-induced neurotoxicity via extracellular signal-regulated kinase 1/2-dependent nuclear factor erythroid 2-related factor 2 activation. Mol Pharmacol. 2008 Jun;73(6):1785-95.
2308 Proc Soc Exp Biol Med 66:512 (1947); J Lab Clin Med 38:873 (1951)
2309 Eur J Clin Pharmacol 7:89 (1969); Arzneim Forsch 22:830 (1972)
2310 Chorvat RJ. Peripherally restricted CB1 receptor blockers. Bioorg Med Chem Lett. 2013 Sep 1;23(17):4751-60.
2311 Knani I, et al. Targeting the endocannabinoid/CB1 receptor system for treating obesity in Prader-Willi syndrome. Mol Metab. 2016 Oct 22;5(12):1187-1199.
2312 Mukhopadhyay B, et al. Cannabinoid receptor 1 promotes hepatocellular carcinoma initiation and progression through multiple mechanisms. Hepatology. 2015 May;61(5):1615-26.
2313 Neef S, et al. Reduction of SR Ca2+ leak and arrhythmogenic cellular correlates by SMP-114, a novel CaMKII inhibitor with oral bioavailability. Basic Res Cardiol. 2017 Jul;112(4):45.
2314 J. Cosmet. Dermatol. (2006), 5(3), 196-203; Skin Ther. Lett. (2004), 9(6), 1-3; J. Microbiol. Biotechnol. (2010), 20(8), 1204-1209
2315 Fluticasone
2316 Ishii N, et al. Antipruritic effect of the topical phosphodiesterase 4 inhibitor E6005 ameliorates skin lesions in a mouse atopic dermatitis model. J Pharmacol Exp Ther. 2013 Jul;346(1):105-12.
2317 Andoh T, et al. Topical E6005, a novel phosphodiesterase 4 inhibitor, attenuates spontaneous itch-related responses in mice with chronic atopy-like dermatitis. Exp Dermatol. 2014 May;23(5):359-61.
2318 Robb CM, et al. Chemically induced degradation of CDK9 by a proteolysis targeting chimera (PROTAC). Chem Commun (Camb). 2017 Jul 4;53(54):7577-7580.
2319 Wagman JD, et al. The effect of fluphenazine decanoate on glucocorticoid production, reproductive cyclicity, and the behavioral stress response in the Persian onager (Equus hemionus onager). Zoo Biol. 2015 Nov;34(6):525-34.
2320 Uchida H, et al. Dose and dosing frequency of long-acting injectable antipsychotics: a systematic review of PET and SPECT data and clinical implications. J Clin Psychopharmacol. 2014 Dec;34(6):728-35.
2321 Weiss RB, et al. Long-acting neuroleptic use for reproductive management of non-domestic ungulates using the domestic goat (Capra hircus) as a model. Zoo Biol. 2014 May-Jun;33(3):204-11.
2322 PCT Int. Appl. (2011), WO 2011060746 A1 20110526.
2323 Friesland A, et al. Small molecule targeting Cdc42-intersectin interaction disrupts Golgi organization and suppresses cell motility. Proc Natl Acad Sci U S A. 2013 Jan 22;110(4):1261-6.
2324 Chou YY, et al. Identification and Characterization of a Novel Broad-Spectrum Virus Entry Inhibitor. J Virol. 2016 Apr 14;90(9):4494-510.
2325 Kongsamut, S., et al., Iloperidone binding to human and rat dopamine and 5-HT receptors. Eur J Pharmacol, 1996. 317(2-3): p. 417-23.
2326 Sainati, S.M., et al., Safety, tolerability, and effect of food on the pharmacokinetics of iloperidone (HP 873), a potential atypical antipsychotic. J Clin Pharmacol, 1995. 35(7): p. 713-20.
2327 Albers, L.J., A. Musenga, and M.A. Raggi, Iloperidone: a new benzisoxazole atypical antipsychotic drug. Is it novel enough to impact the crowded atypical antipsychotic market? Expert Opin Investig Drugs, 2008. 17(1): p. 61-75.
2328 J Cardiovasc Pharmacol 36:376 (2000); Br J Pharmacol 133:625 (2001); Eur Heart J 23:1481 (2003)
2329 Pottayil Govindan Nair Sasikumar, et al. 1,3,4-oxadiazole and 1,3,4-thiadiazole derivatives as immunomodulators. WO2015033301A1.
2330 Bazhin AV, et al. The novel mitochondria-targeted antioxidant SkQ1 modulates angiogenesis and inflammatory micromilieu in a murine orthotopic model of pancreatic cancer. Int J Cancer. 2016 Jul 1;139(1):130-9.
2331 Weniger M, et al. The Analgesic Effect of the Mitochondria-Targeted Antioxidant SkQ1 in Pancreatic Inflammation. Oxid Med Cell Longev. 2016;2016:4650489.
2332 Lee D, et al. Discovery of Novel Pyruvate Dehydrogenase Kinase 4 Inhibitors for Potential Oral Treatment of Metabolic Diseases. J Med Chem. 2019 Jan 24;62(2):575-588.
2333 Carcinogenesis 18:1343 (1997); Cancer Res. 64:6424 (2004)
2334 Zhang J, et al. A small molecule FAK kinase inhibitor, GSK2256098, inhibits growth and survival of pancreatic ductal adenocarcinoma cells. Cell Cycle. 2014;13(19):3143-9.
2335 Thanapprapasr D, et al. PTEN Expression as a Predictor of Response to Focal Adhesion Kinase Inhibition in Uterine Cancer. Mol Cancer Ther. 2015 Jun;14(6):1466-75.
2336 Goyal L, et al. TAS-120 Overcomes Resistance to ATP-Competitive FGFR Inhibitors in Patients with FGFR2 Fusion-Positive Intrahepatic Cholangiocarcinoma. Cancer Discov. 2019 Aug;9(8):1064-1079.
2337 Kalyukina M, et al. TAS-120 Cancer Target Binding: Defining Reactivity and Revealing the First Fibroblast Growth Factor Receptor 1 (FGFR1) Irreversible Structure. ChemMedChem. 2019 Feb 19;14(4):494-500.
2338 Lamarca A, et al. Molecular targeted therapies: Ready for "prime time" in biliary tract cancer [published online ahead of print, 2020 Mar 12]. J Hepatol. 2020;S0168-8278(20)30165-3.
2339 Żymańczyk-Duda E, et al. Reductive capabilities of different cyanobacterial strains towards acetophenone as a model substrate - Prospect of applications for chiral building blocks synthesis. Bioorg Chem. 2019 Feb 25. pii: S0045-2068(18)31467-6.
2340 Hariharan S, et al. Assessment of the biological and pharmacological effects of the alpha nu beta3 and alpha nu beta5 integrinreceptor antagonist, Cilengitide (EMD 121974), in patients with advanced solid tumors. Ann Oncol. 2007 Aug;18(8):1400-7.
2341 Liebel, F., et al., Anti-inflammatory and anti-itch activity of sertaconazole nitrate. Arch Dermatol Res, 2006. 298(4): p. 191-9.
2342 Pfaller, M.A. and D.A. Sutton, Review of in vitro activity of sertaconazole nitrate in the treatment of superficial fungal infections. Diagn Microbiol Infect Dis, 2006. 56(2): p. 147-52.
2343 Sur, R., et al., Anti-inflammatory activity of sertaconazole nitrate is mediated via activation of a p38-COX-2-PGE2 pathway. J Invest Dermatol, 2008. 128(2): p. 336-44.
2344 N Engl J Med 298:289 (1978); 302:250 (1980); Drugs 20:179 (1980)
2345 Owusu BY, et al. Inhibition of pro-HGF activation by SRI31215, a novel approach to block oncogenic HGF/MET signaling. Oncotarget. 2016 May 17;7(20):29492-506.
2346 Patel PD, et al. Paralog-selective Hsp90 inhibitors define tumor-specific regulation of HER2. Nat Chem Biol. 2013 Nov;9(11):677-684.
2347 Phytochem 46:177 (1997); Neoplasa 56:387 (2009); Bioorg Med Chem Lett 20:1037 ((2010); African J Pharm Pharmacol 5: 1937 (2011)
2348 Chung S, Suzuki H, Miyamoto T, et al. Development of an orally-administrative MELK-targeting inhibitor that suppresses the growth of various types of human cancer. Oncotarget. 2012 Dec 21.
2349 Ji W, et al. OTSSP167 Abrogates Mitotic Checkpoint through Inhibiting Multiple Mitotic Kinases. PLoS One. 2016 Apr 15;11(4):e0153518.
2350 Cho YS, et al. The crystal structure of MPK38 in complex with OTSSP167, an orally administrative MELK selective inhibitor. Biochem Biophys Res Commun. 2014 Apr 25;447(1):7-11.
2351 Jurmeister S, et al. Identification of potential therapeutic targets in prostate cancer through a cross-species approach. EMBO Mol Med. 2018 Feb 5. pii: e8274.
2352 Meel MH, et al. MELK inhibition in Diffuse Intrinsic Pontine Glioma. Clin Cancer Res. 2018 Jul 30. pii: clincanres.0924.2018.
2353 Hart PH, et al. Terpinen-4-ol, the main component of the essential oil of Melaleuca alternifolia (tea tree oil), suppresses inflammatory mediator production by activated human monocytes. Inflamm Res. 2000 Nov;49(11):619-26.
2354 Shapira S, et al. Terpinen-4-ol: A Novel and Promising Therapeutic Agent for Human Gastrointestinal Cancers. PLoS One. 2016 Jun 8;11(6):e0156540.
2355 Sulkowski PL, et al. 2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologousrecombination and induces PARP inhibitor sensitivity. Sci Transl Med. 2017 Feb 1;9(375).
2356 Jun Yan He, et al. Salicin as a Multipurpose Therapeutic Approach for Colon Cancer.
2357 Li Y, et al. D(-)-Salicin inhibits the LPS-induced inflammation in RAW264.7 cells and mouse models. Int Immunopharmacol. 2015 Jun;26(2):286-94. |Am J Med Sci 80:273 (1880); Arch Intern Med 101:997 (1958)
2358 Zhou H, et al. NSAID sulindac and its analog bind RXRalpha and inhibit RXRalpha-dependent AKT signaling. Cancer Cell. 2010 Jun 15;17(6):560-73.
2359 Chen L, et al. Modulation of nongenomic activation of PI3K signalling by tetramerization of N-terminally-cleaved RXRα. Nat Commun. 2017 Jul 17;8:16066.
2360 Ibrahim Abdelwahab S, et al. In vitro and in vivo anti-inflammatory activities of columbin through the inhibition of cycloxygenase-2 and nitric oxide but not the suppression of NF-κB translocation. Eur J Pharmacol. 2012 Mar 5;678(1-3):61-70.
2361 A J Nok, et al. Columbin inhibits cholesterol uptake in bloodstream forms of Trypanosoma brucei-A possible trypanocidal mechanism.J Enzyme Inhib Med Chem. 2005 Aug;20(4):365-8.
2362 Yang G, et al. Development and validation of an UPLC-MS/MS method for the quantification of columbin in biological matrices: Applications to absorption, metabolism, and pharmacokinetic studies. J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Oct 1;1002:13-8
2363 Wang F, et al. Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation. Science. 2013 May 3;340(6132):622-6.
2364 Miller AT, et al. Conversion of antigen-specific effector/memory T cells into Foxp3-expressing Treg cells by inhibition of CDK8/19. Sci Immunol. 2019 Oct 25;4(40). pii: eaaw2707.
2365 Martin, Matthew W.; Newcomb, John; Nunes, Joseph J.; et al. Structure-Based Design of Novel 2-Amino-6-phenyl-pyrimido[5',4':5,6]pyrimido[1,2-a]benzimidazol-5(6H)-ones as Potent and Orally Active Inhibitors of Lymphocyte Specific Kinase (Lck): Synthesis, SAR, and In Vivo Anti-Inflammatory Activity. Journal of Medicinal Chemistry (2008), 51(6), 1637-1648.
2366 Liew, Chin Y.; Ma, Xiao H.; Liu, Xianghui; Yap, Chun W. SVM Model for Virtual Screening of Lck Inhibitors. Journal of Chemical Information and Modeling (2009), 49(4), 877-885.
2367 Nieminen, M.S., et al., Levosimendan: current data, clinical use and future development. Heart Lung Vessel, 2013. 5(4): p. 227-245.
2368 Papp, Z., et al., Levosimendan: molecular mechanisms and clinical implications: consensus of experts on the mechanisms of action of levosimendan. Int J Cardiol, 2012. 159(2): p. 82-7.
2369 Landoni, G., et al., Effects of levosimendan on mortality and hospitalization. A meta-analysis of randomized controlled studies. Crit Care Med, 2012. 40(2): p. 634-46. |Pharmacol Toxicol 74:244 (1994);Cardiovasc Drud Rev 14:286 (1996)
2370 Rosenthal AS, et al. An inhibitor of the Cdc2-like kinase 4 (Clk4).
2371 Huang PH, et al. Emodin and Aloe-Emodin Suppress Breast Cancer Cell Proliferation through ER α Inhibition. Evid Based Complement Alternat Med. 2013;2013:376123.
2372 Liu K, et al. Aloe-emodin suppresses prostate cancer by targeting the mTOR complex 2. Carcinogenesis. 2012 Jul;33(7):1406-11.
2373 Li SW, et al. Antiviral activity of aloe-emodin against influenza A virus via galectin-3 up-regulation. Eur J Pharmacol. 2014 Sep 5;738:125-32.
2374 Suboj P, et al. Aloe emodin inhibits colon cancer cell migration/angiogenesis by downregulating MMP-2/9, RhoB and VEGF via reduced DNA binding activity of NF-κB. Eur J Pharm Sci. 2012 Apr 11;45(5):581-91.
2375 Katz A, et al. Selectivity of digitalis glycosides for isoforms of human Na,K-ATPase. J Biol Chem. 2010 Jun 18;285(25):19582-92.
2376 Wu SH, et al. Bufalin induces apoptosis in vitro and has Antitumor activity against human lung cancer xenografts in vivo. Environ Toxicol. 2017 Apr;32(4):1305-1317.
2377 Martin KR, et al. A Potent and Selective ULK1 Inhibitor Suppresses Autophagy and Sensitizes Cancer Cells to Nutrient Stress. iScience. 2018 Oct 26;8:74-84.
2378 Toxicol Appl Pharmacol 1:240 (1959); N Engl J Med 308:357 (1983); 320:1238 (1989)
2379 US20180360805.
2380 Ponnusamy S, et al. Novel Selective Agents for the Degradation of Androgen Receptor Variants to Treat Castration-Resistant Prostate Cancer. Cancer Res. 2017 Nov 15;77(22):6282-6298.
2381 Deng G, et al. Selective inhibition of mutant isocitrate dehydrogenase 1 (IDH1) via disruption of a metal binding network by an allosteric small molecule. J Biol Chem. 2015 Jan 9;290(2):762-74.
2382 Preparation of quinazolinediones as Kif15 kinesin inhibitors for treating cellular proliferative disorders. Pat. Appl. Publ. (2004), US 20040053948 A1 20040318.
2383 Teng F, et al. Production of d-glucuronic acid from myo-inositol using Escherichia coli whole-cell biocatalyst overexpressing a novel myo-inositol oxygenase from Thermothelomyces thermophile. Enzyme Microb Technol. 2019 Aug;127:70-74.
2384 Cesen MH, et al. Siramesine triggers cell death through destabilisation of mitochondria, but not lysosomes. Cell Death Dis. 2013 Oct 3;4:e818.
2385 Spirkoski J, et al. Mast cell apoptosis induced by siramesine, a sigma-2 receptor agonist. Biochem Pharmacol. 2012 Dec 15;84(12):1671-80.
2386 Skuza G, et al. The synergistic effect of selective sigma receptor agonists and uncompetitive NMDA receptor antagonists in the forced swim test in rats. J Physiol Pharmacol. 2006 Jun;57(2):217-29.
2387 Agrimol B, et al. Agrimol B suppresses adipogenesis through modulation of SIRT1-PPAR gamma signal pathway. Biochem Biophys Res Commun. 2016 Aug 26;477(3):454-60.
2388 T Nagatomo, et al. Binding Characteristics of &lt;sup&gt;3&lt;/sup&gt;H-dihydroalprenolol to Beta-Adrenoceptors of Rat Heart Treated With Neuraminidase. Jpn J Pharmacol. 1983 Aug;33(4):851-7.
2389 A S Manning, et al. Abrupt Withdrawal of Chronic Beta-Blockade: Adaptive Changes in Cyclic AMP and Contractility. J Mol Cell Cardiol. 1981 Nov;13(11):999-1009.
2390 Hu S, et al. Discovery and characterization of SY-1365, a selective, covalent inhibitor of CDK7. Cancer Res. 2019 May 7.
2391 Shanhu Hu, et al. SY-1365, a potent and selective CDK7 inhibitor, exhibits promising anti-tumor activity in multiple preclinical models of aggressive solid tumors.
2392 Dongcheng Dai, et al. Antiviral drugs for treatment of arenavirus infection. WO2013123215A2.
2393 Dennis P. Curran, et al. Synthesis of and intermediates for camptothecins. WO1999001456A1.
2394 Br. J. Pharmacol. (2011), 162(5), 1213-1224; Free Radical Biol. Med. (2008), 44(7), 1465-74; Free Radical Biol. Med. (1999), 27(9-10), 1103-13
2395 Su-Lin Lee,et al Identification and Characterization of a Novel Integrin-Linked Kinase Inhibitor.J Med Chem. 2011 Sep 22; 54(18): 6364–6374
2396 Liu TM, et al. OSU-T315: a novel targeted therapeutic that antagonizes AKT membrane localization and activation of chronic lymphocytic leukemia cells. Blood. 2015 Jan 8;125(2):284-95.
2397 Allen, P.J., Creatine metabolism and psychiatric disorders: Does creatine supplementation have therapeutic value. Neurosci Biobehav Rev, 2012. 36(5): p. 1442-62.
2398 Levey, A.S., et al., Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med, 2006. 145(4): p. 247-54. |J Biol Chem 81:73 (1929); JACS 93:5552 (1971)
2399 Nakao S et al. Design and synthesis of prostate cancer antigen-1 (PCA-1/ALKBH3) inhibitors as anti-prostate cancer drugs. Bioorg Med Chem Lett, 2014 Feb 15, 24(4):1071-4.
2400 Biochem. Pharmacol. (1966), 15(1), 49-54; Br. J. Pharmacol. Chemother. (1964), 23, 313-29; J. Physiol. (1962), 162, 105-20,
2401 Zaneta Nikolovska-Coleska, et al. Small molecule inhibitors of mcl-1 and uses thereof. WO2015153959A2.
2402 Mahajan S, et al. VX-509 is a potent and selective Janus kinase 3 (JAK3) inhibitor that attenuates inflammation in animal models of autoimmune disease. J Pharmacol Exp Ther. 2015 Mar 11. pii: jpet.114.221176.
2403 Cansfield AD, et al. CZ415, a Highly Selective mTOR Inhibitor Showing in Vivo Efficacy in a Collagen Induced Arthritis Model. ACS Med Chem Lett. 2016 Jun 10;7(8):768-73.
2404 Kerres N, et al. Chemically Induced Degradation of the Oncogenic Transcription Factor BCL6. Cell Rep. 2017 Sep 19;20(12):2860-2875.
2405 Mikołaj Słabicki, et al. Small-molecule-induced polymerization triggers degradation of BCL6. Nature. 2020 Nov 18.
2406 Ho H, et al. Structural basis for dual-mode inhibition of the ABC transporter MsbA. Nature. 2018 May;557(7704):196-201.
2407 J. Pharm. Pharmacol. (1963), 15, 212-14. ; J. Chem. Eng. Data (1962), 7, 265-6; (1957), GB 774635 19570515,
2408 Zhao Y, et al. Depression Promotes Hepatocellular Carcinoma Progression through a Glucocorticoids Mediated Up-Regulation of PD-1 Expression in Tumor infiltrating NK Cells. Carcinogenesis. 2019 Feb 4.
2409 Li K, et al. Development of small-molecule immune checkpoint inhibitors of PD-1/PD-L1 as a new therapeutic strategy for tumour immunotherapy. J Drug Target. 2019 Mar;27(3):244-256.
2410 Zhang H, et al. Utilizing VEGF165b mutant as an effective immunization adjunct to augment antitumor immune response. Vaccine. 2019 Apr 3;37(15):2090-2098.
2411 Mengyuan Li, et al. KALRN mutations promote antitumor immunity and immunotherapy response in cancer. J Immunother Cancer. 2020 Oct;8(2):e000293.
2412 Bhatia S, et al. Targeting HSP90 dimerization via the C terminus is effective in imatinib-resistant CML and lacks the heat shock response.Blood. 2018 Jul 19;132(3):307-320.
2413 Burlison JA, et al. Novobiocin: redesigning a DNA gyrase inhibitor for selective inhibition of hsp90.J Am Chem Soc. 2006 Dec 6;128(48):15529-36.
2414 Rong P, et al. Photosensitizer loaded nano-graphene for multimodality imaging guided tumor photodynamic therapy. Theranostics. 2014 Jan 15;4(3):229-39.
2415 Shams M, et al. Development of photodynamic therapy regimens that control primary tumor growth and inhibit secondary disease. Cancer Immunol Immunother. 2015 Mar;64(3):287-97.
2416 Arzneim. Forsch. (1961), 11, 1119-26; Acta Pharmacol. Toxicol. (1955), 11, 148-55; Helv. Chim. Acta (1941), 24, 36-40E.
2417 https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20190727044343N1
2418 Iaconelli J, et al. HDAC6 Inhibitors Modulate Lys49 Acetylation and Membrane Localization of β-Catenin in Human iPSC-Derived Neuronal Cells. ACS Chemical Biology (2015), 10(3), 883-890.
2419 Tang D, et al. Metformin facilitates BG45-induced apoptosis via an anti-Warburg effect in cholangiocarcinoma cells. Oncol Rep. 2018 Apr;39(4):1957-1965.
2420 Hongbin Guo, et al. Metabolites profiling and pharmacokinetics of troxipide and its pharmacodynamics in rats with gastric ulcer. Sci Rep. 2020 Aug 12;10(1):13619.
2421 K Kusugami, et al. Troxipide, a novel antiulcer compound, has inhibitory effects on human neutrophil migration and activation induced by various stimulants. Dig Liver Dis. 2000 May;32(4):305-11.
2422 Jun Tang, et al. Effect of parecoxib, a novel intravenous cyclooxygenase type-2 inhibitor, on the postoperative opioid requirement and quality of pain control. Anesthesiology
2423 J L Mateos, et al.[Selective inhibitors of cyclooxygenase-2 (COX-2), celecoxib and parecoxib: a systematic review]. Drugs Today (Barc). 2010 Feb;46 Suppl A:1-25.
2424 Bo Wang, et al. Chronic administration of parecoxib exerts anxiolytic-like and memory enhancing effects and modulates synaptophysin expression in mice. BMC Anesthesiol. 2017 Nov 13;17(1):152.
2425 Lin-Yong Li, et al. Parecoxib inhibits glioblastoma cell proliferation, migration and invasion by upregulating miRNA-29c. Biol Open. 2017 Mar 15;6(3):311-316.
2426 Oyama K, et al. Antibacterial Effects of Glycyrrhetinic Acid and Its Derivatives on Staphylococcus aureus. PLoS One. 2016 Nov 7;11(11):e0165831.
2427 Ma FY, et al. A pathogenic role for c-Jun amino-terminal kinase signaling in renal fibrosis and tubular cell apoptosis. J Am Soc Nephrol. 2007 Feb;18(2):472-84.
2428 Vasilevskaya IA, et al. Inhibition of JNK Sensitizes Hypoxic Colon Cancer Cells to DNA-Damaging Agents. Clin Cancer Res. 2015 Sep 15;21(18):4143-52.
2429 Ma FY, et al. Blockade of the c-Jun amino terminal kinase prevents crescent formation and halts established anti-GBM glomerulonephritis in the rat. Lab Invest. 2009 Apr;89(4):470-84.
2430 Qi W, et al. Selective inhibition of Ezh2 by a small molecule inhibitor blocks tumor cells proliferation. Proc Natl Acad Sci U S A. 2012 Dec 26;109(52):21360-5.
2431 Yu G, et al. Protective effects of LM22A-4 on injured spinal cord nerves. Int J Clin Exp Pathol. 2015 Jun 1;8(6):6526-32. eCollection 2015.
2432 Kajiya M, et al. BDNF mimetic compound LM22A-4 regulates cementoblast differentiation via the TrkB-ERK/Akt signaling cascade. Int Immunopharmacol. 2014 Apr;19(2):245-52
2433 Drabikowska AK, et al. Inhibitor properties of some 5-substituted uracil acyclonucleosides, and 2,2'-anhydrouridines versus uridine phosphorylase from E. coli and mammalian sources. Biochem Pharmacol. 1987 Dec 1;36(23):4125-8.
2434 Cherrill DA, et al. Demeclocycline treatment in the syndrome of inappropriate antidiuretic hormone secretion. Ann Intern Med. 1975 Nov;83(5):654-6.
2435 Singer I, et al. Demeclocycline-induced nephrogenic diabetes insipidus. In-vivo and in-vitro studies. Ann Intern Med. 1973 Nov;79(5):679-83.
2436 Forrest JN Jr, et al. Superiority of demeclocycline over lithium in the treatment of chronic syndrome of inappropriate secretion of antidiuretic hormone. N Engl J Med. 1978 Jan 26;298(4):173-7.
2437 Zhang Z, et al. Analytical method for the determination of meptyldinocap as the 2,4-dinitro-octylphenol metabolite in cucumber and soil using LC-MS/MS and a study of the residues in a Chinese cucumber field ecosystem. Pest Manag Sci. 2014 Jan;70(1):97-102.
2438 Acta Pharmacol Toxicol 4:265 (1948); Ecotoxicol Environ Saf 6:149 (1982)|
2439 Beckman ML, et al. Stereoselective inhibition of serotonin transporters by antimalarial compounds. Neurochem Int. 2014 Jul;73:98-106.
2440 Moffat D, et al. Discovery of 2-(6-{[(6-fluoroquinolin-2-yl)methyl]amino}bicyclo[3.1.0]hex-3-yl)-N-hydroxypyrimidine-5-carboxamide (CHR-3996), a class I selective orally active histone deacetylase inhibitor. J Med Chem. 2010 Dec 23;53(24):8663-78.
2441 J Chem Soc 1969:33; Phytochem 11:3479 (1972); Anticancer Res 21:1905 (2001); Phytother Res 15:441 (2001); African J Biotech 10:16337 (2011)
2442 Kawasaki S, et al. Effects of hypnotic bromovalerylurea on microglial BV2 cells. J Pharmacol Sci. 2017 Jun;134(2):116-123.
2443 Mrongovius RI, et al. Comparison of the bromureide sedative-hypnotic drugs, bromvaletone (bromisoval) and carbromal, and their chloro analogues in mice. Clin Exp Pharmacol Physiol. 1976 Sep-Oct;3(5):443-7.
2444 Hartman JC, et al. Evaluation of the endothelin receptor antagonists ambrisentan, darusentan, bosentan, and sitaxsentan as substrates and inhibitors of hepatobiliary transporters in sandwich-cultured human hepatocytes. Can J Physiol Pharmacol. 2010 Jun;88
2445 Tilton RG, et al. Attenuation of pulmonary vascular hypertension and cardiac hypertrophy with sitaxsentan sodium, an orally active ET(A) receptor antagonist. Pulm Pharmacol Ther. 2000;13(2):87-97.
2446 Rondelet B, et al. Sildenafil added to sitaxsentan in overcirculation-induced pulmonary arterial hypertension. Am J Physiol Heart Circ Physiol. 2010 Oct;299(4):H1118-23. Epub 2010 Aug 6.
2447 Li MH, et al. Antitumor Activity of a Novel Sphingosine-1-Phosphate 2 Antagonist, AB1, in Neuroblastoma. J Pharmacol Exp Ther. 2015 Sep;354(3):261-8.
2448 Guo C, et al. Discovery of aryloxy tetramethylcyclobutanes as novel androgen receptor antagonists. J Med Chem. 2011 Nov 10;54(21):7693-704.
2449 Han X, et al. Discovery of ARD-69 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Androgen Receptor (AR) for the Treatment of Prostate Cancer. J Med Chem. 2019 Jan 24;62(2):941-964.
2450 Billiard J, et al. Quinoline 3-sulfonamides inhibit lactate dehydrogenase A and reverse aerobic glycolysis in cancer cells. Cancer Metab. 2013 Sep 6;1(1):19.
2451 Cal West Med 37:405 (1932)
2452 Angewandte Chem IntL Ed 12:869 (1973); 37:1802 (1998); Horm Metab Res 19:233 (1987)
2453 J Chem Soc 1949: 3271; Biotechnol Biochem 61: 890 (1997)
2454 Moerke NJ, et al. Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G. Cell. 2007 Jan 26;128(2):257-67.
2455 Yi T, et al. 4EGI-1 targets breast cancer stem cells by selective inhibition of translation that persists in CSC maintenance, proliferation and metastasis. Oncotarget. 2014 Aug 15;5(15):6028-37.
2456 Wu M, et al. Anti-Cancer Effect of Cap-Translation Inhibitor 4EGI-1 in Human Glioma U87 Cells: Involvement of Mitochondrial Dysfunction and ER Stress. Cell Physiol Biochem. 2016;40(5):1013-1028. Epub 2016 Dec 12.
2457 https://clinicaltrials.gov/ct2/show/NCT04335123?term=Losartan&cond=COVID-19&draw=2&rank=1 https://clinicaltrials.gov/ct2/show/NCT04643691?term=Losartan&cond=COVID-19&draw=2&rank=2 https://clinicaltrials.gov/ct2/show/NCT04328012?term=Losartan&cond=COVID-19&draw=2&rank=4 https://clinicaltrials.gov/ct2/show/NCT04606563?term=Losartan&cond=COVID-19&draw=2&rank=5 https://clinicaltrials.gov/ct2/show/NCT04447235?term=Losartan&cond=COVID-19&draw=2&rank=6 https://clinicaltrials.gov/ct2/show/NCT04312009?term=Losartan&cond=COVID-19&draw=2&rank=8 https://clinicaltrials.gov/ct2/show/NCT04311177?term=Losartan&cond=COVID-19&draw=2&rank=9 https://clinicaltrials.gov/ct2/show/NCT04340557?term=Losartan&cond=COVID-19&draw=2&rank=10
2458 J Pharmac Pharmacol 15 Suppl 1:97T (1963); J Biol Chem 267:1569 (1992)
2459 Drouin L, et al. Structure enabled design of BAZ2-ICR, a chemical probe targeting the bromodomains of BAZ2A and BAZ2B. J Med Chem. 2015 Mar 12;58(5):2553-9.
2460 J Chem Soc C 1967:842; Indian J Chem Soc 7:977 (1969); J Biol Chem 288:23858 (2013)
2461 Drug Ther. Bull. (1999), 37(8), 57-8; Drugs (1995), 50(2), 317-33; J. Med. Chem. (1967), 10(5), 799-802|
2462 Mollmann, H., et al., Pharmacokinetic/pharmacodynamic evaluation of deflazacort in comparison to methylprednisolone and prednisolone. Pharmaceutical research, 1995. 12(7): p. 1096-1100.
2463 Barnes PJ. Tiotropium bromide. Expert Opin Investig Drugs. 2001 Apr;10(4):733-40.
2464 ZuWallack AR, ZuWallack RL. Tiotropium bromide, a new, once-daily inhaled anticholinergic bronchodilator for chronic-obstructive pulmonary disease. Expert Opin Pharmacother. 2004 Aug;5(8):1827-35.
2465 Lipson DA. Tiotropium bromide. Int J Chron Obstruct Pulmon Dis. 2006;1(2):107-14.
2466 Mamary AJ, Criner GJ. Tiotropium bromide for chronic obstructive pulmonary disease. Expert Rev Respir Med. 2009 Jun;3(3):211-20.
2467 Szmidt M. [The influence of treatment with formoterol, formoterol with tiotropium, formoterol with inhaled glucocorticosteroid and tiotropium on lung functions, tolerance of exercise and simple, morning everyday activities in patients with chronic obstructive pulmonary disease (COPD)]. Pneumonol Alergol Pol. 2012;80(3):255-62.
2468 Seganish WM. Inhibitors of interleukin-1 receptor-associated kinase 4 (IRAK4): a patent review (2012-2015). Expert Opin Ther Pat. 2016 Aug;26(8):917-32.
2469 Lee KL, et al. Discovery of Clinical Candidate 1-{[(2S,3S,4S)-3-Ethyl-4-fluoro-5-oxopyrrolidin-2-yl]methoxy}-7-methoxyisoquinoline-6-carboxamide (PF-06650833), a Potent, Selective Inhibitor of Interleukin-1 Receptor Associated Kinase 4 (IRAK4), by Fragment-Based Drug Design. J Med Chem. 2017 Jul 13;60(13):5521-5542.
2470 J Pharmacol Exp Ther 105:166 (1952); Toxicol Appl Pharmacol 18:185 (1971); Crit Care Clin 7:639 (1991)
2471 Ching-Wen C, et al. p-Hydroxyacetophenone suppresses nuclear factor-κB-related inflammation in nociceptive and inflammatory animal models. J Nat Med. 2017 Apr;71(2):422-432.
2472 Ning Xi, et al. Abstract 1755: CT053PTSA, a novel c-MET and VEGFR2 inhibitor, potently suppresses angiogenesis and tumor growth. Cancer Res 2014;74(19 Suppl):Abstract nr 1755.
2473 Toxicol Appl Pharmacol 22:332 (1972); Curr Ther Res 59:420 (1998)
2474 Tetrahedron 8:64 (1960); Phytochemistry 11:2283 (1972); 24:1027 (1985)
2475 Zhang N, et al. Biodegradable polymeric micelles encapsulated JK184 suppress tumor growth through inhibiting Hedgehog signaling pathway. Nanoscale. 2015 Feb 14;7(6):2609-24.
2476 Colavito SA, et al. Significance of glioma-associated oncogene homolog 1 (GLI1) expression in claudin-low breast cancer and crosstalk with the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway. Breast Cancer Res. 2014 Sep 25;16(5):444.
2477 https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=Hydrocortisone&cntry=&state=&city=&dist=
2478 Bocos C, et al. Effect of etofibrate on bile production in the normolipidemic rat. Gen Pharmacol. 1995 May;26(3):537-42.
2479 Zhang D, et al. Echinacoside inhibits amyloid fibrillization of HEWL and protects against Aβ-induced neurotoxicity. Int J Biol Macromol. 2014 Sep 2;72C:243-253.
2480 Zhu M, et al. Transient exposure to echinacoside is sufficient to activate Trk signaling and protect neuronal cells from rotenone. J Neurochem. 2013 Feb;124(4):571-80.
2481 Li F, et al. Antiosteoporotic activity of echinacoside in ovariectomized rats. Phytomedicine. 2013 Apr 15;20(6):549-57.
2482 Li F, et al. Echinacoside promotes bone regeneration by increasing OPG/RANKL ratio in MC3T3-E1 cells. Fitoterapia. 2012 Dec;83(8):1443-50.
2483 Li X, et al. Echinacoside ameliorates D-galactosamine plus lipopolysaccharide-induced acute liver injury in mice via inhibition of apoptosis and inflammation. Scand J Gastroenterol. 2014 Aug;49(8):993-1000.
2484 Tang C, et al. Echinacoside inhibits breast cancer cells by suppressing the Wnt/β-catenin signaling pathway. Biochem Biophys Res Commun. 2020 Mar 19. pii: S0006-291X(20)30530-1.
2485 Rohde JM, et al. Discovery and optimization of piperazine-1-thiourea-based human phosphoglycerate dehydrogenase inhibitors. Bioorg Med Chem. 2018 May 1;26(8):1727-1739.
2486 Phytochemistry 42: 443 (1996)
2487 Pharmazie 8: 584 (1953); Biochim Biophys Acta 1001: 1 (1989)|
2488 Huang YT, et al. Aristolochic acid I interferes with the expression of BLCAP tumor suppressor gene in human cells. Toxicol Lett. 2018 Jul;291:129-137.
2489 Helv Chim Acta 27:1748 (1944); J Pharmacol Exp Therap 131:115 (1961)
2490 Oliveira MM, et al. Dihydrocaffeic Acid Prevents UVB-Induced Oxidative Stress Leading to the Inhibition of Apoptosis and MMP-1 Expression via p38 Signaling Pathway. Oxid Med Cell Longev. 2019 Jan 17;2019:2419096.
2491 Foster P, et al. The Selective PI3K Inhibitor XL147 (SAR245408) Inhibits Tumor Growth and Survival and Potentiates the Activity of Chemotherapeutic Agents in Preclinical Tumor Models. Mol Cancer Ther. 2015 Apr;14(4):931-40.
2492 Hasler CM, et al. Specific binding to protein kinase C by ingenol and its induction of biological responses. Cancer Res. 1992 Jan 1;52(1):202-8.
2493 Shen Y et al. Discovery of a Potent, Selective, and Cell-Active Dual Inhibitor of Protein Arginine Methyltransferase 4 and Protein Arginine Methyltransferase 6. J Med Chem. 2016 Sep 15.
2494 Wang J, et al. Identification of DK419, a potent inhibitor of Wnt/β-catenin signaling and colorectal cancer growth. Bioorg Med Chem. 2018 Nov 1;26(20):5435-5442.
2495 https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=NALBUPHINE+&cntry=&state=&city=&dist=&Search=Search
2496 N. R. Mirza, et al. NS11394 [3 -[5-(1-Hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-biphenyl-2-carbonitrile], a Unique Subtype-Selective GABAA Receptor Positive Allosteric Modulator: In Vitro Actions, Pharmacokinetic Properties and in Vivo Anxiolytic Efficacy. THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS. 2008 Jul.
2497 G. Munro, J. A., et al. Comparison of the Novel Subtype-Selective GABAA Receptor-Positive Allosteric Modulator NS11394 [3′-[5-(1-Hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-biphenyl-2-carbonitrile] with Diazepam, Zolpidem, Bretazenil, and Gaboxadol in Rat Models of Inflammatory and Neuropathic Pain. Journal of Pharmacology and Experimental Therapeutics December 2008, 327 (3) 969-981.
2498 Martine Hofmann, et al. Assessment of the effects of NS11394 and L-838417, a2/3 subunit-selective GABAA receptor-positive allosteric modulators, in tests for pain, anxiety, memory and motor function. Behavioural Pharmacology 2012, 23:790–801.
2499 Antimicrob Agents Chemother 1:221 (1972); 3:657 (1973); 6:177 (1974); 9:140, 10:814 (1976)
2500 Dae Yong Kim, et al. Costunolide-A Bioactive Sesquiterpene Lactone with Diverse Therapeutic Potential. Int J Mol Sci. 2019 Jun; 20(12): 2926.
2501 Minyan Wei, et al. Costunolide induces apoptosis and inhibits migration and invasion in H1299 lung cancer cells. Oncol Rep. 2020 Jun;43(6):1986-1994.
2502 Zhangxiao Peng, et al. Costunolide and dehydrocostuslactone combination treatment inhibit breast cancer by inducing cell cycle arrest and apoptosis through c-Myc/p53 and AKT/14-3-3 pathway.Sci Rep. 2017; 7: 41254.
2503 Tetrahedron 25:4617(1969); An Acad Brasil Cienc 42 (suplemento): 45 (1970)
2504 Appl. Microbiol 7:199 (1959); Appl Environ Microbiol 9:278 (1961); IARC Monographs 4:259 (1974)
2505 http://en.irct.ir/trial/47475
2506 Wu FL , et al. Gelatinases-stimuli nanoparticles encapsulating 5-fluorouridine and 5-aza-2'-deoxycytidine enhance the sensitivity of gastric cancer cells to chemical therapeutics. Cancer Lett. 2015 Jul 10;363(1):7-16.
2507 Hu N, et al. Strengthening Gastric Cancer Therapy by Trastuzumab-Conjugated Nanoparticles with Simultaneous Encapsulation of Anti-MiR-21 and 5-Fluorouridine. Cell Physiol Biochem. 2017;44(6):2158-2173.
2508 Glazer RI, et al. Association of cell lethality with incorporation of 5-fluorouracil and 5-fluorouridine into nuclear RNA in human colon carcinoma cells in culture. Mol Pharmacol. 1982 Mar;21(2):468-73.
2509 Kanzawa F, et al. Differences between 5-fluoro-2'-deoxyuridine and 5-fluorouridine in their cytotoxic effect on growth of murine lymphoma L5178Y cells in in vivo and in vitro systems. Eur J Cancer. 1980 Aug;16(8):1087-92.
2510 Sun XP, et al. ABT-737 Induces Apoptosis of Gastric Carcinoma Cells In Vitro and In Vivo.J Int Med Res. 2012;40(4):1251-64.
2511 Clerc P, et al. Polster BM.Rapid Detection of an ABT-737-Sensitive Primed for Death State in Cells Using Microplate-Based Respirometry.PLoS One. 2012;7(8):e42487. Epub 2012 Aug 3.
2512 Konopleva M, et al. Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia. Cancer Cell. 2006 Nov;10(5):375-88.
2513 Helv Chim Acta 4:100 (1921);19:1402 (1936); J Chem Soc 1950:1983; J Lab Clin Med 47:20 (1956); Fitoterapia 55:279 (1984); Antiviral Res 7:127 (1987); 10:289 (1988); 11:255 (1989)|
2514 Su X, et al. Glycyrrhizic acid: A promising carrier material for anticancer therapy. Biomed Pharmacother. 2017 Sep 5;95:670-678
2515 Wang LY, et al. Glycyrrhizic acid increases glucagon like peptide-1 secretion via TGR5 activation in type 1-like diabetic rats. Biomed Pharmacother. 2017 Sep 4;95:599-604.
2516 Li C, et al. Glycyrrhizin, a Direct HMGB1 Antagonist, Ameliorates Inflammatory Infiltration in a Model of Autoimmune Thyroiditis via Inhibition of TLR2-HMGB1 Signaling. Thyroid. 2017 May;27(5):722-731.
2517 Xia Zhao, et al. A Simple Injectable Moldable Hydrogel Assembled from Natural Glycyrrhizic Acid with Inherent Antibacterial Activity. ACS Appl. Bio Mater. 2020, 3, 1, 648–653.
2518 Lei X, et al. The FDA-approved natural product dihydroergocristine reduces the production of the Alzheimer's disease amyloid-β peptides. Sci Rep. 2015 Nov 16;5:16541.
2519 Drugs (1978), 15(3), 198-217; Dis. Nerv. Syst. (1975), 36(7), 361-4; Arzneim. Forsch. (1965), 15(8), 841-3
2520 Kotschy A, et al. The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models. Nature. 2016 Oct 27;538(7626):477-482.
2521 Antimicrob Agents Chemother 33:1167 (1987); 34:89 (1990)
2522 Toxicology. 3rd ed. Wiley , NY 1981-1982, 2768; Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Hoboken, NJ. 2004.,3530
2523 Lee G, et al. Anti-inflammatory and antioxidant mechanisms of urolithin B in activated microglia. Phytomedicine. 2019 Mar 1;55:50-57.
2524 Rodriguez J, et al. Urolithin B, a newly identified regulator of skeletal muscle mass. J Cachexia Sarcopenia Muscle. 2017 Aug;8(4):583-597.
2525 J Pharmacol 8:351 (1977); Biochem Pharmacol 28:141 (1979); Arzneim Forsch 32:915, 955 (1982)
2526 Xu S, et al. Discovery of a novel orally active small-molecule gp130 inhibitor for the treatment of ovarian cancer. Mol Cancer Ther. 2013 Jun;12(6):937-49.
2527 Kim YY, et al. HM71224, a selective Bruton's tyrosine kinase inhibitor, attenuates the development of murine lupus. Arthritis Res Ther. 2017 Sep 26;19(1):211.
2528 Thompson JE, et al. Photochemical preparation of a pyridone containing tetracycle: a Jak protein kinase inhibitor. Bioorg Med Chem Lett. 2002 Apr 22;12(8):1219-23.
2529 Nakagawa R, et al. Pyridone 6, a pan-JAK inhibitor, ameliorates allergic skin inflammation of NC/Nga mice via suppression of Th2 and enhancement of Th17. J Immunol. 2011 Nov 1;187(9):4611-20.
2530 Papeo G, et al. Discovery of 2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118): A Potent, Orally Available, and Highly Selective PARP-1 Inhibitor for Cancer Therapy. J Med Chem. 2015 Sep 10;58(17):6875-98.
2531 Fernandez-Alba, J., et al., Fenticonazole nitrate for treatment of vulvovaginitis: efficacy, safety, and tolerability of 1-gram ovules, administered as ultra-short 2-day regimen. J Chemother, 2004. 16(2): p. 179-86.
2532 Rofida Albash, et al. Ultra-deformable liposomes containing terpenes (terpesomes) loaded fenticonazole nitrate for treatment of vaginal candidiasis: Box-Behnken design optimization, comparative ex vivo and in vivo studies. Drug Deliv. 2020 Dec;27(1):1514-1523.
2533 Sun K, et al. Subcellular distribution and biotransformation of phenanthrene in pakchoi after inoculation with endophytic Pseudomonas sp. as probed using HRMS coupled with isotope-labeling. Environ Pollut. 2018 Jun;237:858-867.
2534 Dupuy J, et al. Effect and localization of phenanthrene in maize roots. Chemosphere. 2016 Apr;149:130-6.
2535 https://clinicaltrials.gov/ct2/show/NCT04462367?term=Pancuronium&cond=Covid19&draw=2&rank=1
2536 Scott JS, et al. Novel acidic 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor with reduced acyl glucuronide liability: the discovery of 4-[4-(2-adamantylcarbamoyl)-5-tert-butyl-pyrazol-1-yl]benzoic acid (AZD8329). J Med Chem. 2012 Nov 26;55(22):10136-47.
2537 Aneja B, et al. Design and development of Isatin-triazole hydrazones as potential inhibitors of microtubule affinity-regulating kinase 4 for the therapeutic management of cell proliferation and metastasis. Eur J Med Chem. 2019 Feb 1;163:840-852.
2538 Griswold DE, et al. SK&amp;F 86002: a structurally novel anti-inflammatory agent that inhibits lipoxygenase- and cyclooxygenase-mediated metabolism of arachidonic acid. Biochem Pharmacol. 1987 Oct 15;36(20):3463-70.
2539 Frasch SC, et al. p38 mitogen-activated protein kinase-dependent and -independent intracellular signal transduction pathways leading to apoptosis in human neutrophils. J Biol Chem. 1998 Apr 3;273(14):8389-97.
2540 M J DiMartino, et al. Pharmacologic characterization of the antiinflammatory properties of a new dual inhibitor of lipoxygenase and cyclooxygenase. Agents Actions. 1987 Feb;20(1-2):113-23.
2541 L A Marshall, et al. Inhibitors of the p38 mitogen-activated kinase modulate IL-4 induction of low affinity IgE receptor (CD23) in human monocytes. J Immunol. 1998 Dec 1;161(11):6005-13.
2542 Reed D, et al. Identification and characterization of the first small molecule inhibitor of MDMX. J Biol Chem. 2010 Apr 2;285(14):10786-96.
2543 Bista M, et al. On the mechanism of action of SJ-172550 in inhibiting the interaction of MDM4 and p53. PLoS One. 2012;7(6):e37518.
2544 Wu X, et al. Discovery of Nonquinone Substrates for NAD(P)H: Quinone Oxidoreductase 1 (NQO1) as Effective Intracellular ROS Generators for the Treatment of Drug-Resistant Non-Small-Cell Lung Cancer. J Med Chem. 2018 Dec 27;61(24):11280-11297.
2545 Smaill JB, et al. Tyrosine kinase inhibitors. 17. Irreversible inhibitors of the epidermal growth factor receptor: 4-(phenylamino)quinazoline- and 4-(phenylamino)pyrido[3,2-d]pyrimidine-6-acrylamides bearing additional solubilizing functions. J Med Chem. 2000 Apr 6;43(7):1380-97.
2546 Djerf Severinsson EA, et al. The pan-ErbB receptor tyrosine kinase inhibitor canertinib promotes apoptosis of malignant melanoma in vitro and displays anti-tumor activity in vivo. Biochem Biophys Res Commun. 2011 Oct 28;414(3):563-8.
2547 McAndrews KM, et, al. Mechanisms associated with biogenesis of exosomes in cancer. Mol Cancer. 2019 Mar 30;18(1):52.
2548 Lee SW, et al. Phenolic compounds isolated from Psoralea corylifolia inhibit IL-6-induced STAT3 activation. Planta Med. 2012 Jun;78(9):903-6.
2549 https://clinicaltrials.gov/ct2/show/NCT04467931?term=HYDRALAZINE&cond=COVID-19&draw=2&rank=1
2550 Pundir S, et al. VR23: A Quinoline-Sulfonyl Hybrid Proteasome Inhibitor That Selectively Kills Cancer via Cyclin E-Mediated Centrosome Amplification. Cancer Res. 2015 Oct 1;75(19):4164-4175.
2551 Lee Hoyun, et al. Preparation of quinoline sulfonyl derivatives for the treatment of cancer. From PCT Int. Appl. (2014), WO 2014134705 A1 20140912.
2552 Tournilhac O, et al. Impact of frontline fludarabine and cyclophosphamide combined treatment on peripheral blood stem cell mobilization in B-cell chronic lymphocytic leukemia. Blood. 2004 Jan 1;103(1):363-5. Epub 2003 Sep 11.
2553 Liang YB, et al. Downregulated SOCS1 expression activates the JAK1/STAT1 pathway and promotes polarization of macrophages into M1 type. Mol Med Rep. 2017 Nov;16(5):6405-6411.
2554 Sanhes L, et al. Fludarabine-induced apoptosis of B chronic lymphocytic leukemia cells includes early cleavage of p27kip1 by caspases. Leukemia. 2003 Jun;17(6):1104-11.
2555 Weiss L, et al. Fludarabine in combination with cyclophosphamide decreases incidence of GVHD and maintainseffective graft-versus-leukemia effect after allogeneic stem cell transplantation in murinelymphocytic leukemia. Bone Marrow Transplant. 2003 Jan;31(1):11-5.
2556 Frank DA,et al. Fludarabine-induced immunosuppression is associated with inhibition of STAT1 signaling. Nat Med. 1999 Apr;5(4):444-7.
2557 Shaoqing Hu, et al.Evaluation of anti-apoptotic, anti-injury and antihepatitis&#x0D; B virus effects of isochlorogenic acid C in&#x0D; vitro. Journal of Medicinal Plants Research Vol. 6(16), pp. 3199-3206 30 April, 2012
2558 Therapeutische Monatsh 17:208 (1903)
2559 J Pharmacol Exp Ther 130:222 (1960); Acta Pharmacol Toxicol 47:263 (1980)
2560 Tet Letters 1965: 3523; 1967: 220
2561 Chen YY, et al. Methyl cinnamate inhibits adipocyte differentiation via activation of the CaMKK2-AMPK pathwayin 3T3-L1 preadipocytes. J Agric Food Chem. 2012 Feb 1;60(4):955-63.
2562 https://clinicaltrials.gov/ct2/show/NCT04351763?term=Verapamil&cond=Covid19&draw=2&rank=1
2563 Gargett CE, et al. The isoquinoline derivative KN-62 a potent antagonist of the P2Z-receptor of human lymphocytes. Br J Pharmacol. 1997 Apr;120(8):1483-90.
2564 Ravi RG, et al. Potent P2X7 Receptor Antagonists: Tyrosyl Derivatives Synthesized Using a Sequential Parallel Synthetic Approach. Drug Dev Res. 2001 Oct;54(2):75-87.
2565 Manosso LM, et al. Antidepressant-like effect of zinc is dependent on signaling pathways implicated in BDNF modulation. Prog Neuropsychopharmacol Biol Psychiatry. 2015 Jun 3;59:59-67.
2566 G M Bressa. et al. S-adenosyl-l-methionine (SAMe) as antidepressant: meta-analysis of clinical studies. Acta Neurol Scand Suppl. 1994;154:7-14.
2567 Wadie I Najm, et al. S-adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: a double-blind cross-over trial. [ISRCTN36233495]. BMC Musculoskelet Disord. 2004 Feb 26;5:6.
2568 Shelly C Lu, et al. S-adenosylmethionine in liver health, injury, and cancer. Physiol Rev. 2012 Oct;92(4):1515-42.
2569 Bodin NO, et al. Bacampicillin: a new orally well-absorbed derivative of ampicillin. Antimicrob Agents Chemother. 1975 Nov;8(5):518-25.
2570 Reprod Toxicol 12:217 (1998); JAMA 281:2189 (1999); 282:637 (1999)
2571 Afobazole, From Wikipedia
2572 Ganeshkumar Y, et al. Picroside I and Picroside II from Tissue Cultures of &lt;i&gt;Picrorhiza kurroa&lt;/i&gt;. Pharmacognosy Res. 2017 Dec;9(Suppl 1):S53-S56.
2573 Sen Zhang, et al. Picroside I inhibits asthma phenotypes by regulating Tbet/GATA-3 ratio and Th1/Th2 balance in a murine model of asthma. Tropical Journal of Pharmaceutical Research September 2018; 17 (9): 1777-1782.
2574 Buset Ríos N, Rodríguez Esparragón F, Fernández-Andrade Rodríguez C, et al. Vascular and metabolic properties of manidipine . Nefrologia. 2011;31(3):268-74.
2575 Costa S, Zimetti F, Pedrelli M, et al. Manidipine reduces pro-inflammatory cytokines secretion in human endothelial cells and macrophages. Pharmacol Res. 2010 Sep;62(3):265-70.
2576 Cavalieri L, Cremonesi G. Metabolic effects of manidipine. Am J Cardiovasc Drugs. 2009;9(3):163-76. doi: 10.2165/00129784-200909030-00004.
2577 Roca-Cusachs A, Triposkiadis F. Antihypertensive effect of manidipine. Drugs. 2005;65 Suppl 2:11-9.
2578 Nagaoka A. Pharmacologic characteristics of a new calcium antagonist, manidipine: beneficial effects on renal circulation and vascular changes. Am Heart J. 1993 Feb;125(2 Pt 2):560-5.
2579 Hwee DT, et al. Fast skeletal muscle troponin activator tirasemtiv increases muscle function and performance in the B6SJL-SOD1G93A ALS mouse model. PLoS One. 2014 May 7;9(5):e96921.
2580 Eckburg PB, et al. Safety, Tolerability, Pharmacokinetics, and Drug Interaction Potential of SPR741, an Intravenous Potentiator, after Single and Multiple Ascending Doses and When Combined with β-Lactam Antibiotics in Healthy Subjects. Antimicrob Agents Chemother. 2019 Aug 23;63(9). pii: e00892-19.
2581 Corbett D, et al. Potentiation of Antibiotic Activity by a Novel Cationic Peptide: Potency and Spectrum of Activity of SPR741. Antimicrob Agents Chemother. 2017 Jul 25;61(8). pii: e00200-17.
2582 Larsen ST, et al. Effects of R-(+)- and S-(-)-limonene on the respiratory tract in mice. Hum Exp Toxicol. 2000 Aug;19(8):457-66.
2583 Zhu S, et al. Comprehensive Interactome Analysis Reveals that STT3B is Required for the N-Glycosylation of Lassa Virus Glycoprotein. J Virol. 2019 Sep 11. pii: JVI.01443-19.
2584 Lopez-Sambrooks C, et al. Oligosaccharyltransferase inhibition induces senescence in RTK-driven tumor cells. Nat Chem Biol. 2016 Dec;12(12):1023-1030.
2585 Wakeling AE, et al. A potent specific pure antiestrogen with clinical potential. Cancer Res. 1991 Aug 1;51(15):3867-73.
2586 Osborne CK, et al. Fulvestrant: an oestrogen receptor antagonist with a novel mechanism of action. Br J Cancer. 2004 Mar;90 Suppl 1:S2-6.
2587 Garner F, et al. RAD1901: a novel, orally bioavailable selective estrogen receptor degrader that demonstrates antitumor activity in breast cancer xenograft models. Anticancer Drugs. 2015 Oct;26(9):948-56
2588 Yu X, et al.MiR-214 increases the sensitivity of breast cancer cells to tamoxifen and fulvestrant through inhibition of autophagy.Mol Cancer. 2015 Dec 15;14:208.
2589 Julia Kuhn, et al. GPR30 estrogen receptor agonists induce mechanical hyperalgesia in the rat. Eur J Neurosci. 2008 Apr;27(7):1700-9. |Drugs (2011), 71(3), 363-380; Int. J. Cancer (1994), 56(2), 295-300; Cancer Res. (1991), 51(15), 3867-73
2590 Alexander LT, et al. Type II Inhibitors Targeting CDK2. ACS Chem Biol. 2015 Sep 18;10(9):2116-25.
2591 Jones K, et al. Cancer Drug Discovery 2010: from molecules to medicine. Expert Rev Clin Pharmacol. 2010 Sep;3(5):613-5.
2592 C J Fowler, et al. The nature of the inhibition of rat liver monoamine oxidase types A and B by the acetylenic inhibitors clorgyline, l-deprenyl and pargyline. Biochem Pharmacol. 1982 Nov 15;31(22):3555-61.
2593 Fuentes JA, et al. Central mediation of the antihypertensive effect of pargyline in spontaneously hypertensive rats. Eur J Pharmacol. 1979 Jul 15;57(1):21-7.
2594 Hyung Tae Lee, et al. Effects of the monoamine oxidase inhibitors pargyline and tranylcypromine on cellular proliferation in human prostate cancer cells. Oncol Rep. 2013 Oct;30(4):1587-92.
2595 Palma-Vargas JM, et al. Small-molecule selectin inhibitor protects against liver inflammatory response after ischemia and reperfusion. J Am Coll Surg. 1997 Oct;185(4):365-72.
2596 Hegde SS, et al. Functional role of M2 and M3 muscarinic receptors in the urinary bladder of rats in vitro and in vivo. Br J Pharmacol, 1997, 120(8), 1409-1418.
2597 https://clinicaltrials.gov/ct2/show/NCT04631536?term=Folic+acid&cond=COVID-19&draw=2&rank=1 https://trialsearch.who.int/Trial2.aspx?TrialID=PACTR202005599385499
2598 Levin ED, et al. Effects of tobacco smoke constituents, anabasine and anatabine, on memory and attention in female rats. J Psychopharmacol. 2014 Oct;28(10):915-22.
2599 Benedict T Green, et al. Actions of piperidine alkaloid teratogens at fetal nicotinic acetylcholine receptors. Neurotoxicol Teratol. May-Jun 2010;32(3):383-90.
2600 Hoppe Seyler's Z Physiol Chem 244:181 (1936); Drugs 21:90 (1981); Gastroenterology 91:1007 (1986)|
2601 Jackson H, et al. Influence of ursodeoxycholic acid on the mortality and malignancy associated with primary biliary cirrhosis: a population-based cohort study. Hepatology. 2007 Oct;46(4):1131-7.
2602 Kumar D, et al. Use of ursodeoxycholic acid in liver diseases. J Gastroenterol Hepatol. 2001 Jan;16(1):3-14.
2603 Biao Nie, et al. Specific Bile Acids Inhibit Hepatic Fatty Acid Uptake in Mice. Hepatology. 2012 Oct;56(4):1300-10.
2604 Eur. J. Pharmacol. (2005), 506(3), 237-240; J. Pharmacol. Exp. Ther. (1968), 160(1), 243-8; J. Clin. Pharmacol. J. New Drugs (1968), 8(1), 42-53
2605 J Rheumatol 2:437 (1975); 3:305 (1976); Eur J Clin Pharmacol 19:431 (1981)
2606 Stock NS, et al. 5-Lipoxygenase-activating protein (FLAP) inhibitors. Part 4: development of 3-[3-tert-butylsulfanyl-1-[4-(6-ethoxypyridin-3-yl)benzyl]-5-(5-methylpyridin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropionic acid (AM803), a potent, oral, once daily FLAP inhibitor. J Med Chem. 2011 Dec 8;54(23):8013-29.
2607 Lorrain DS, et al. Pharmacology of AM803, a novel selective five-lipoxygenase-activating protein (FLAP) inhibitor in rodent models of acute inflammation. Eur J Pharmacol. 2010 Aug 25;640(1-3):211-8.
2608 Morita S, et al. Targeting ABL-IRE1α Signaling Spares ER-Stressed Pancreatic β Cells to Reverse Autoimmune Diabetes. Cell Metab. 2017 Apr 4;25(4):883-897.e8.
2609 Qiu XL, et al. Synthesis and biological evaluation of a series of novel inhibitor of Nek2/Hec1 analogues. J Med Chem. 2009 Mar 26;52(6):1757-67.
2610 Vranesic I, et al. AFQ056/mavoglurant, a novel clinically effective mGluR5 antagonist: identification, SAR and pharmacological characterization. Bioorg Med Chem. 2014 Nov 1;22(21):5790-5803.
2611 Jacquemont AS, et, al. Epigenetic modification of the FMR1 gene in fragile X syndrome is associated with differential response to the mGluR5 antagonist AFQ056. Sci Transl Med. 2011 Jan 5;3(64):64ra1.
2612 Petrov D, et, al. Mavoglurant as a treatment for Parkinson's disease. Expert Opin Investig Drugs. 2014 Aug;23(8):1165-79.
2613 Phytochemistry (Elsevier) (1977), 16(1), 9-18; J. Pharm. Pharmacol. (1987), 39(3), 153-7; J. Pharm. Pharmacol. (1987), 39(9), 752-4
2614 Gillespie RJ, et al. Antagonists of the human adenosine A2A receptor. Part 3: Design and synthesis of pyrazolo[3,4-d]pyrimidines, pyrrolo[2,3-d]pyrimidines and 6-arylpurines. Bioorg Med Chem Lett. 2008 May 1;18(9):2924-9.
2615 Zhang Z, et al. Discovery of potent and selective spiroindolinone MDM2 inhibitor, RO8994, for cancer therapy. Bioorg Med Chem. 2014 Aug 1;22(15):4001-4009.
2616 Tan, A.K., et al. Identification of the site of covalent attachment of nafcillin, a reversible suicide inhibitor of beta-lactamase. Biochem J, 1992. 281 ( Pt 1): p. 191-6.
2617 Palmer, D.L., et al. Bacterial wound colonization after broad-spectrum versus narrow-spectrum antibiotics. Ann Thorac Surg, 1995. 59(3): p. 626-31.
2618 Lawrence I. Mortin, et al. Rapid Bactericidal Activity of Daptomycin against Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus Peritonitis in Mice as Measured with Bioluminescent Bacteria. Antimicrob Agents Chemother. 2007 May; 51(5): 1787–1794.
2619 Horne DB, et al. Discovery of TRPM8 Antagonist ( S)-6-(((3-Fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)carbamoyl)nicotinic Acid (AMG 333), a Clinical Candidate for the Treatment of Migraine. J Med Chem. 2018 Sep 27;61(18):8186-8201.
2620 Antimicrob Agents Chemother 1:221 (1972); 3:657 (1973); 10:814 (1976)
2621 https://clinicaltrials.gov/ct2/show/NCT04742725?term=GLUTATHIONE&cond=covid&draw=2&rank=2
2622 Arzneim Forsch 27:1173 (1977); Therapie 35:5 (1980)
2623 Arzneim Forsch 30:1091, 1098 (1980); Clin Ther 4:121 (1981); Med Clin 76:18 (1981)
2624 Naga Rajiv Lakkaniga,et al. Discovery of SP-96, the first non-ATP-competitive Aurora Kinase B inhibitor, for reduced myelosuppression.Eur J Med Chem. 2020 Jul 12;203:112589.
2625 Chaturvedi A, et al. Pan-mutant-IDH1 inhibitor BAY1436032 is highly effective against human IDH1 mutant acute myeloid leukemia in vivo. Leukemia. 2017 Oct;31(10):2020-2028.
2626 Wang Y, et al. Nootkatone, a neuroprotective agent from Alpiniae Oxyphyllae Fructus, improves cognitive impairment in lipopolysaccharide-induced mouse model of Alzheimer's disease. Int Immunopharmacol. 2018 Sep;62:77-85.
2627 Wang Y, et al. Nootkatone, a neuroprotective agent from Alpiniae Oxyphyllae Fructus, improves cognitive impairment in lipopolysaccharide-induced mouse model of Alzheimer's disease. Int Immunopharmacol. 2018 Sep;62:77-85.
2628 J Pharm Pharmacol 54:1521 (2002)|
2629 Tian J, et al. Nerol-induced apoptosis associated with the generation of ROS and Ca&lt;sup&gt;2+&lt;/sup&gt; overload in saprotrophic fungus &lt;i&gt;Aspergillus flavus&lt;/i&gt;. Appl Microbiol Biotechnol. 2018 Aug;102(15):6659-6672.
2630 Tian J, et al. Nerol triggers mitochondrial dysfunction and disruption via elevation of Ca&lt;sup&gt;2+&lt;/sup&gt; and ROS in &lt;i&gt;Candida albicans&lt;/i&gt;. Int J Biochem Cell Biol. 2017 Apr;85:114-122.
2631 Bill MA, et al. The small molecule curcumin analog FLLL32 induces apoptosis in melanoma cells via STAT3inhibition and retains the cellular response to cytokines with anti-tumor activity. Mol Cancer. 2010 Jun 25;9:165.
2632 Lin L, et al. Novel STAT3 phosphorylation inhibitors exhibit potent growth-suppressive activity in pancreaticand breast cancer cells. Cancer Res. 2010 Mar 15;70(6):2445-54.
2633 Dhawan NS, et al. Small molecule stabilization of the KSR inactive state antagonizes oncogenic Ras signalling. Nature. 2016 Aug 24;537(7618):112-116.
2634 Iwatani-Yoshihara M, et al. Discovery and Characterization of a Eukaryotic Initiation Factor 4A-3-Selective Inhibitor That Suppresses Nonsense-Mediated mRNA Decay. ACS Chem Biol. 2017 Jul 21;12(7):1760-1768.
2635 hepatotoxic at clinical dose (600mg)
2636 Pharmacol Rev 45:309 (1993); J Biol Chem 281:22021 (2006); J Neural Transm 115:1087 (2008)
2637 Xie F, et al. Identification of a Potent Inhibitor of CREB-Mediated Gene Transcription with Efficacious in Vivo Anticancer Activity. J Med Chem. 2015 Jun 25;58(12):5075-87.
2638 Zhang B, et al. C1q-TNF-related protein-3 attenuates pressure overload-induced cardiac hypertrophy by suppressing the p38/CREB pathway and p38-induced ER stress. Cell Death Dis. 2019 Jul 8;10(7):520.
2639 Qin Y, et al. Interfering MSN-NONO complex-activated CREB signaling serves as a therapeutic strategy for triple-negative breast cancer. Sci Adv. 2020 Feb 19;6(8):eaaw9960.
2640 Guichard SM, et al. AZD2014, an inhibitor of mTORC1 and mTORC2, is highly effective in ER+ breast cancer when administered using intermittent or continuous schedules. Mol Cancer Ther. 2015 Nov;14(11):2508-18.
2641 Seng KY, et al. Population pharmacokinetic analysis of isoniazid, acetylisoniazid, and isonicotinic acid in healthy volunteers. Antimicrob Agents Chemother. 2015 Nov;59(11):6791-9.
2642 Raina K, et al. PROTAC-induced BET protein degradation as a therapy for castration-resistant prostate cancer. Proc Natl Acad Sci U S A. 2016 Jun 28;113(26):7124-9.
2643 Kudo Y, et al. Development of amyloid imaging PET probes for an early diagnosis of Alzheimer's disease. Minim Invasive Ther Allied Technol. 2006;15(4):209-13.
2644 Furukawa K, et al. Amyloid PET in mild cognitive impairment and Alzheimer's disease with BF-227: comparison to FDG-PET. J Neurol. 2010 May;257(5):721-7.
2645 Farmakol Toxsikol 20(6):46 (1957)
2646 Arzneim forsch 27:866 (1977); Anal Profiles Drug Subs 9:543 (1980)
2647 Biochem J 20: 293, 300 (1926)|
2648 Arici M, et al. Association between genetic polymorphism and levothyroxine bioavailability in hypothyroid patients. Endocr J. 2018 Mar 28;65(3):317-323.
2649 Corriveau S, et al. Levothyroxine treatment generates an abnormal uterine contractility patterns in an in vitro animalmodel. J Clin Transl Endocrinol. 2015 Sep 9;2(4):144-149.
2650 hepatotoxic at clinical dose (300mg)
2651 Lobachevsky PN, Vasireddy RS, Broadhurst S, Protection by methylproamine of irradiated human keratinocytes correlates with reduction of DNA damage. Int J Radiat Biol. 2011 Mar;87(3):274-83.
2652 Sprung CN, Vasireddy RS, Karagiannis TC, Methylproamine protects against ionizing radiation by preventing DNA double-strand breaks. Mutat Res. 2010 Oct 13;692(1-2):49-52.
2653 Martin RF, Broadhurst S, Reum ME, In vitro studies with methylproamine: a potent new radioprotector. Cancer Res. 2004 Feb 1;64(3):1067-70.
2654 Duffy RA, et al. Rolapitant (SCH 619734): a potent, selective and orally active neurokininNK1 receptor antagonist with centrally-mediated antiemetic effects inferrets. Pharmacol Biochem Behav. 2012 Jul;102(1):95-100.
2655 Dydrogesterone, From Wikipedia, the free encyclopedia |Drugs Aging (1997), 11(4), 309-32; Steroids (1966), 7(1), 1-10; Int. J. Fertil. (1964), 9, 585-95
2656 Buti M, et al. Drugs in development for hepatitis B. Drugs. 2005;65(11):1451‐1460.
2657 Keam SJ. Telbivudine. Drugs. 2007;67(13):1917‐1929.
2658 Quinazolinedione derivatives useful for treating cellular proliferative disorders and disorders associated with Kif15 kinesin activity are described. US 20040053948 A1.
2659 Zhang E, et al. Glycycoumarin inhibits hepatocyte lipoapoptosis through activation of autophagy and inhibition of ER stress/GSK-3-mediated mitochondrial pathway. Sci Rep. 2016 Nov 30;6:38138.
2660 Song X, et al. Glycycoumarin exerts anti-liver cancer activity by directly targeting T-LAK cell-originated protein kinase. Oncotarget. 2016 Oct 4;7(40):65732-65743.
2661 https://trialsearch.who.int/Trial2.aspx?TrialID=ISRCTN16269648
2662 Lin-Feng Wang, et al. Tert-butylhydroquinone ameliorates doxorubicin-induced cardiotoxicity by activating Nrf2 and inducing the expression of its target genes. Am J Transl Res. 2015; 7(10): 1724–1735.
2663 Hu H, et al. Dehydrocorydaline inhibits cell proliferation, migration and invasion via suppressing MEK1/2-ERK1/2 cascade in melanoma.Onco Targets Ther. 2019 Jul 2;12:5163-5175.
2664 XIAOJING SHI, et al. Tert-butylhydroquinone attenuates the ethanol-induced apoptosis of and activates the Nrf2 antioxidant defense pathway in H9c2 cardiomyocytes.Int J Mol Med. 2016 Jul; 38(1): 123–130.
2665 Sukumari-Ramesh S, et al. Post-Injury Administration of Tert-butylhydroquinone Attenuates Acute Neurological Injury AfterIntracerebral Hemorrhage in Mice.J Mol Neurosci. 2016 Apr;58(4):525-31.
2666 https://clinicaltrials.gov/ct2/show/NCT04467931?term=Guanfacine&cond=covid&draw=2&rank=1
2667 Liza Leventhal, et al. Phosphodiesterase 9 inhibitor and levodopa therapy. WO 2017070293 A1.
2668 Sharifzadeh, M., et al., Post-training intrahippocampal infusion of nicotine-bucladesine combination causes a synergistic enhancement effect on spatial memory retention in rats. Eur J Pharmacol, 2007. 562(3): p. 212-20.
2669 Mafune, E., M. Takahashi, and N. Takasugi, Effect of vehicles on percutaneous absorption of bucladesine (dibutyryl cyclic AMP) in normal and damaged rat skin. Biol Pharm Bull, 1995. 18(11): p. 1539-43.
2670 Rundfeldt, C., et al., The stable cyclic adenosine monophosphate analogue, dibutyryl cyclo-adenosine monophosphate (bucladesine), is active in a model of acute skin inflammation. Arch Dermatol Res, 2012.
2671 Salehi F, et al. Effect of bucladesine, pentoxifylline, and H-89 as cyclic adenosine monophosphate analog, phosphodiesterase, and protein kinase A inhibitor on acute pain. Fundam Clin Pharmacol. 2017 Aug;31(4):411-419.
2672 Shimojo M, et al. The cholinergic gene locus is coordinately regulated by protein kinase A II in PC12 cells. J Neurochem. 1998 Sep;71(3):1118-26.
2673 New Zealand J Ecology 23:161 (1999); Toxicol Rev 25:213 (2006)
2674 Arzneim Forsch 34:1010 (1984)
2675 Bettayeb K, et al. CR8, a potent and selective, roscovitine-derived inhibitor of cyclin-dependent kinases. Oncogene. 2008 Oct 2;27(44):5797-807.
2676 Kabadi SV, et al. CR8, a novel inhibitor of CDK, limits microglial activation, astrocytosis, neuronal loss, and neurologic dysfunction after experimental traumatic brain injury. J Cereb Blood Flow Metab. 2014 Mar;34(3):502-13.
2677 Słabicki M, et al. The CDK inhibitor CR8 acts as a molecular glue degrader that depletes cyclin K [published online ahead of print, 2020 Jun 3]. Nature. 2020;10.1038/s41586-020-2374-x.
2678 T Ochiai, et al. Pharmacological studies on 6-amino-2-fluoromethyl-3-(O-tolyl)-4(3H)-quinazolinone (afloqualone), a new centrally acting muscle relaxant. (II) Effects on the spinal reflex potential and the rigidity. Jpn J Pharmacol. 1982 Jun;32(3):427-38.
2679 Y Kudo, et al. Effects of afloqualone on vestibular nystagmus and the lateral vestibular nucleus. Jpn J Pharmacol. 1989 Aug;50(4):515-9.
2680 Vet Parasitol 13:145 (1983); Vet Rec 113:315 (1983)
2681 Sibhghatulla Shaikh, et al. Aptiom (Eslicarbazepine Acetate) as a Dual Inhibitor of β-Secretase and Voltage-Gated Sodium Channel: Advancement in Alzheimer's Disease-Epilepsy Linkage via an Enzoinformatics Study. CNS &amp; Neurological Disorders Drug Targets Volume 13 , Issue 7 , 2014.
2682 https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=Folinic+acid&cntry=&state=&city=&dist=
2683 Rudnicki SA, Berry JD, Ingersoll E, et al. Dexpramipexole effects on functional decline and survival in subjects with amyotrophic lateral sclerosis in a Phase II study: subgroup analysis of demographic and clinical characteristics. Amyotroph Lateral Scler Frontotemporal Degener. 2013 Jan;14(1):44-51.
2684 Alavian KN, Dworetzky SI, Bonanni L, et al. Effects of dexpramipexole on brain mitochondrial conductances and cellular bioenergetic efficiency. Brain Res. 2012 Mar 29;1446:1-11.
2685 Cudkowicz M, Bozik ME, Ingersoll EW, et al. The effects of dexpramipexole (KNS-760704) in individuals with amyotrophic lateral sclerosis. Nat Med. 2011 Nov 20;17(12):1652-6.
2686 Bozik ME, Mather JL, Kramer WG, et al. Safety, tolerability, and pharmacokinetics of KNS-760704 (dexpramipexole) in healthy adult subjects. J Clin Pharmacol. 2011 Aug;51(8):1177-85.
2687 Cheah BC, Kiernan MC. Dexpramipexole, the R(+) enantiomer of pramipexole, for the potential treatment of amyotrophic lateral sclerosis. IDrugs. 2010 Dec;13(12):911-20.
2688 Drugs (1996), 52(6), 899-927; Invest. Radiol. (1990), 25 Suppl 1S113-4; Br. J. Radiol. (1986), 59(706), 987-91
2689 Chapman J, et al. RSV604, a novel inhibitor of respiratory syncytial virus replication. Antimicrob Agents Chemother. 2007 Sep;51(9):3346-53.
2690 Challa S, et al. Mechanism of action for respiratory syncytial virus inhibitor RSV604. Antimicrob Agents Chemother. 2015 Feb;59(2):1080-7.
2691 Antimicrob Agents Chemother 9:102 (1976); Am J Trop Med Hyg.24:485 (1975); 28:559 (1979)
2692 Vaseva AV, et al. KRAS Suppression-Induced Degradation of MYC Is Antagonized by a MEK5-ERK5 Compensatory Mechanism. Cancer Cell. 2018 Nov 12;34(5):807-822.e7.
2693 Neuropharmacol 27:399 (1988); Expert Rev Neurotherapeut 3:425 (2003)
2694 Denise RAGEOT, et al. Treatment of neurological disorders. WO2017198346A1.
2695 Chiara Borsari, et al. 4-(Difluoromethyl)-5-(4-((3 R,5 S)-3,5-dimethylmorpholino)-6-(( R)-3-methylmorpholino)-1,3,5-triazin-2-yl)pyridin-2-amine (PQR626), a Potent, Orally Available, and Brain-Penetrant mTOR Inhibitor for the Treatment of Neurological Disorders. J Med Chem. 2020 Nov 25;63(22):13595-13617.
2696 Ngonye Keroletswe, et al. A New 3-Prenyl-2-flavene and Other Extractives from Baphia massaiensis and Their Antimicrobial Activities. Natural Product Communications.
2697 J C Anderson, et al. The Effect of Incorporation of Cloxacillin in Liposomes on Treatment of Experimental Staphylococcal Mastitis in Mice. J Vet Pharmacol Ther. 1986 Sep;9(3):303-9.
2698 W Calame, et al. Influence of Etoposide and Cyclophosphamide on the Efficacy of Cloxacillin and Erythromycin in an Experimental Staphylococcal Infection. Antimicrob Agents Chemother. 1989 Jun;33(6):980-2.
2699 Peter H Nibbering, et al. 99mTc-Labeled UBI 29-41 Peptide for Monitoring the Efficacy of Antibacterial Agents in Mice Infected With Staphylococcus Aureus. J Nucl Med. 2004 Feb;45(2):321-6.
2700 Srivastava M, et al. An inhibitor of nonhomologous end-joining abrogates double-strand break repair and impedes cancer progression. Cell. 2012 Dec 21;151(7):1474-87.
2701 Lin C, et al. Increasing the Efficiency of CRISPR/Cas9-mediated Precise Genome Editing of HSV-1 Virus in Human Cells. Sci Rep. 2016 Oct 7;6:34531.
2702 Camilleri M. LX-1031, a tryptophan 5-hydroxylase inhibitor, and its potential in chronic diarrhea associated with increased serotonin. Neurogastroenterol Motil. 2011 Mar;23(3):193-200.
2703 Camilleri M. LX-1031, a tryptophan 5-hydroxylase inhibitor that reduces 5-HT levels for the potential treatment of irritable bowel syndrome. IDrugs. 2010 Dec;13(12):921-8.
2704 J Soc Cosmet Chem 32:327 (1981)
2705 Liu T, et al. Mechanism of thioesterase-catalyzed chain release in the biosynthesis of the polyether antibiotic Nanchangmycin. Chem Biol. 2008 May;15(5):449-58.
2706 Rausch K, et al. Screening Bioactives Reveals Nanchangmycin as a Broad Spectrum Antiviral Active against Zika Virus. Cell Rep. 2017 Jan 17;18(3):804-815.
2707 WO2018060317.
2708 Raboisson P, et al. Structure-activity relationship study on a novel series of cyclopentane-containing macrocyclic inhibitors of the hepatitis C virus NS3/4A protease leading to the discovery of TMC435350. Bioorg Med Chem Lett. 2008 Sep 1;18(17):4853-8.
2709 Lin TI, et al. In vitro activity and preclinical profile of TMC435350, a potent hepatitis C virus protease inhibitor.Antimicrob Agents Chemother. 2009 Apr;53(4):1377-85. Epub 2009 Jan 26.
2710 Rajagopalan R, et al. Preclinical Characterization and Human Microdose Pharmacokinetics of ITMN-8187, a Nonmacrocyclic Inhibitor of the Hepatitis C Virus NS3 Protease. Antimicrob Agents Chemother. 2016 Dec 27;61(1). pii: e01569-16.
2711 Waldschmidt HV, et al. Structure-Based Design of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2Inhibitors Based on Paroxetine. J Med Chem. 2017 Apr 13;60(7):3052-3069.
2712 N Eng J Med 324:746 (1991); Anal Profiles Drug Subs Excip 22:145 (1993)
2713 Park MH, et al. Anticancer effect of Tectochrysin in colon cancer cell via suppression of NF-kappaB activity and enhancement of death receptor expression. Mol Cancer. 2015 Jun 30;14:124.
2714 Arikawa Y, et al. Discovery of a novel pyrrole derivative 1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine fumarate (TAK-438) as a potassium-competitive acid blocker (P-CAB). J Med Chem, 2012, 55(9), 4446-4456.
2715 Hori Y, et al. 1-[5-(2-Fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine monofumarate (TAK-438), a novel and potent potassium-competitive acid blocker for the treatment of acid-related diseases. J Pharmacol Exp Ther, 2010, 335(1), 231-238.
2716 Cruz HG, et al. Assessment of the abuse liability of a dual orexin receptor antagonist: a crossover study of almorexant and zolpidem in recreational drug users. CNS Drugs. 2014 Apr;28(4):361-72.
2717 Malherbe P, et al. Biochemical and electrophysiological characterization of almorexant, a dual orexin 1 receptor (OX1)/orexin 2 receptor (OX2) antagonist: comparison with selective OX1 and OX2 antagonists. Mol Pharmacol. 2009 Sep;76(3):618-31.
2718 Sifferlen T, et al. Novel pyrazolo-tetrahydropyridines as potent orexin receptor antagonists. Bioorg Med Chem Lett. 2010 Mar 1;20(5):1539-42.
2719 Black SW, et al. Almorexant promotes sleep and exacerbates cataplexy in a murine model of narcolepsy. Sleep. 2013 Mar 1;36(3):325-36.
2720 Dayot S, et al. In vitro, in vivo and ex vivo demonstration of the antitumoral role of hypocretin-1/orexin-A and almorexant in pancreatic ductal adenocarcinoma. Oncotarget. 2018 Jan 9;9(6):6952-6967.
2721 Su Hongjun, Medical composition containing morpholine azomycin phosphate, its formulation and application to prepare the medical preparations as anti-anaerobic bacteria agent, antitrichomonal agent and antiamebic agent
2722 Seitz L, et al. Safety, tolerability, and pharmacology of AB928, a novel dual adenosine receptor antagonist, in a randomized, phase 1 study in healthy volunteers. Invest New Drugs. 2019 Aug;37(4):711-721.
2723 Daniel DiRenzo, et al. AB928, a dual antagonist of the A2aR and A2bR adenosine receptors, relieves adenosine-mediated immune suppression [abstract].
2724 Szucs, T., Cilazapril. A review. Drugs, 1991. 41 Suppl 1: p. 18-24.
2725 Nussberger, J., et al., Repeated administration of the converting enzyme inhibitor cilazapril to normal volunteers. J Cardiovasc Pharmacol, 1987. 9(1): p. 39-44.
2726 Tetrahedron 40: 235 (1984); Eur J Heart Failure 12:1274 (2010)
2727 Zhao G, et al. A Novel, Selective Inhibitor of Fibroblast Growth Factor Receptors That Shows a Potent Broad Spectrum of Antitumor Activity in Several Tumor Xenograft Models. Molecular Cancer Therapeutics (2011), 10(11), 2200-2210.
2728 J Chem Soc 1963:983; 1970:205; Nature 207:1101(1965); Phytomedicine 15:533 (2008)
2729 de Moraes J, et al. Phytol, a diterpene alcohol from chlorophyll, as a drug against neglected tropical diseaseSchistosomiasis mansoni. PLoS Negl Trop Dis. 2014 Jan 2;8(1):e2617. |J Chem Soc 1966: 2144
2730 Conway JG, et al. Inhibition of colony-stimulating-factor-1 signaling in vivo with the orally bioavailable cFMS kinase inhibitor GW2580. Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):16078-83.
2731 Priceman SJ, et al. Targeting distinct tumor-infiltrating myeloid cells by inhibiting CSF-1 receptor: combating tumor evasion of antiangiogenic therapy. Blood. 2010 Feb 18;115(7):1461-71
2732 Conway JG, et al. Effects of the cFMS kinase inhibitor 5-(3-methoxy-4-((4-methoxybenzyl)oxy)benzyl)pyrimidine-2,4-diamine (GW2580) in normal and arthritic rats. J Pharmacol Exp Ther. 2008 Jul;326(1):41-50.
2733 Gos FMWR, et al. Antibacterial Activity of Endophytic Actinomycetes Isolated from the Medicinal Plant Vochysia divergens (Pantanal, Brazil). Front Microbiol. 2017 Sep 6;8:1642.
2734 Yang ZD, et al. Secondary Metabolites and PI3K Inhibitory Activity of Colletotrichum gloeosporioides, a Fungal Endophyte of Uncaria rhynchophylla. Curr Microbiol. 2019 Jul;76(7):904-908.
2735 Hu H, et al. Mutational Landscape of Secondary Glioblastoma Guides MET-Targeted Trial in Brain Tumor. Cell. 2018 Nov 29;175(6):1665-1678.e18.
2736 Ku BM, et al. Transglutaminase 2 inhibitor abrogates renal cell carcinoma in xenograft models. J Cancer Res Clin Oncol. 2014 May;140(5):757-67.
2737 R.T. Schermuly, H. Leuchte, H.A. Ghofrani, et al. Zardaverine and aerosolised iloprost in a model of acute respiratoryfailure. ERJ, 2003 ,22 (2): 342-347.
2738 D. Ukena, K. Rentz, C. Reiber, et al. Effects of the mixed phosphodiesterase III/IV inhibitor, zardaverine, on airway function in patients with chronic airflow obstruction. Respiratory Medicine.1995, 89 ( 6) : 441-444.
2739 Schade FU, Schudt C. The specific type III and IV phosphodiesterase inhibitor zardaverine suppresses formation of tumor necrosis factor by macrophages. European Journal of Pharmacology.1993, 230(1):9-14.
2740 Pan Z, et al. Discovery of selective irreversible inhibitors for Bruton's tyrosine kinase. ChemMedChem. 2007 Jan;2(1):58-61.
2741 Ge C, et al. PCI29732, a Bruton's Tyrosine Kinase Inhibitor, Enhanced the Efficacy of Conventional Chemotherapeutic Agents in ABCG2-Overexpressing Cancer Cells. Cell Physiol Biochem. 2018;48(6):2302-2317.
2742 Honigberg LA, et al. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Proc Natl Acad Sci U S A. 2010;107(29):13075-13080.
2743 Gibbons JA, et al. Pharmacokinetic Drug Interaction Studies with Enzalutamide. Clin Pharmacokinet. 2015 Oct;54(10):1057-69.
2744 Arch Intern Med 105:121 (1960); Austral New Zeal J Surg 39:207 (1969)
2745 Kamel A, et al. Metabolism, pharmacokinetics and excretion of the GABA(A) receptor partial agonist [(14)C]CP-409,092 in rats. Xenobiotica. 2010 Jun;40(6):400-14.
2746 J Med Chem 11:325 (1968); N Engl J Med 307:1037 (1982)
2747 Kim WH, et al. Ethyl gallate induces apoptosis of HL-60 cells by promoting the expression of caspases-8, -9, -3, apoptosis-inducing factor and endonuclease G. Int J Mol Sci. 2012;13(9):11912-22.
2748 Mohan S, et al. In vitro protection of biological macromolecules against oxidative stress and in vivo toxicity evaluation of Acacia nilotica (L.) and ethyl gallate in rats. BMC Complement Altern Med. 2014 Jul 21;14:257.
2749 https://clinicaltrials.gov/ct2/show/NCT04333550?term=DEFEROXAMINE&cond=COVID-19&draw=2&rank=1 https://clinicaltrials.gov/ct2/show/NCT04361032?term=DEFEROXAMINE&cond=COVID-19&draw=2&rank=2 https://clinicaltrials.gov/ct2/show/NCT04389801?term=DEFEROXAMINE&cond=COVID-19&draw=2&rank=3 https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20200506047323N4
2750 Pharmazie 3:5 (1948)|Bull Exp Biol Med 61:291 (1966); Engl J Med 286:141 (1973); Muscle Nerve 20:1146 (1997)
2751 Obst & Gynec 9:610 (1957); J Dent Res 62:135 (1983)
2752 Song JX, et al. HMGB1 is involved in autophagy inhibition caused by SNCA/α-synuclein overexpression: a process modulated by the natural autophagy inducer corynoxine B. Autophagy. 2014 Jan;10(1):144-54.
2753 Sakakibara I, et al. Effect of oxindole alkaloids from the hooks of Uncaria macrophylla on thiopental-induced hypnosis. Phytomedicine. 1998 Apr;5(2):83-6.
2754 N Engl J Med 308:1448 (1983); 310:1545 (1984); 327:782 (1992)
2755 Nebbioso A, et al. Selective class II HDAC inhibitors impair myogenesis by modulating the stability and activity ofHDAC-MEF2 complexes. EMBO Rep. 2009 Jul;10(7):776-82.
2756 Venza I, et al. Class II-specific histone deacetylase inhibitors MC1568 and MC1575 suppress IL-8 expression in human melanoma cells. Pigment Cell Melanoma Res. 2013 Mar;26(2):193-204.
2757 Nebbioso A, et al. HDACs class II-selective inhibition alters nuclear receptor-dependent differentiation. J Mol Endocrinol. 2010 Oct;45(4):219-28.
2758 Kassis H, et al. Class IIa histone deacetylases affect neuronal remodeling and functional outcome after stroke. Neurochem Int. 2016 Jun;96:24-31.
2759 Massey AJ, et al. Preclinical antitumor activity of the orally available heat shock protein 90 inhibitor NVP-BEP800. Mol Cancer Ther. 2010 Apr;9(4):906-19.
2760 Niewidok N, et al. Hsp90 Inhibitors NVP-AUY922 and NVP-BEP800 May Exert a Significant Radiosensitization on Tumor Cells along with a Cell Type-Specific Cytotoxicity. Transl Oncol. 2012 Oct;5(5):356-69. Epub 2012 Oct 1.
2761 Wu J, et al. Irradiation facilitates the inhibitory effect of the heat shock protein 90 inhibitor NVP-BEP800 on the proliferation of malignant glioblastoma cells through attenuation of the upregulation of heat shock protein 70. Exp Ther Med. 2014 Sep;8(3):893-898. Epub 2014 Jun 23.
2762 Zahm DS, et al. Comparison of the locomotor-activating effects of bicuculline infusions into the preoptic area and ventral pallidum. Brain Struct Funct. 2014 Mar;219(2):511-26.
2763 Johnston GA. Advantages of an antagonist: bicuculline and other GABA antagonists. Br J Pharmacol. 2013 May;169(2):328-36.
2764 Alam MM, et al. Validation of the protein kinase PfCLK3 as a multistage cross-species malarial drug target. Science. 2019 Aug 30;365(6456). pii: eaau1682.
2765 Arzneim Forsch 15:1441 (1965)
2766 GuoDong Zhang, et al. Predicting hiCE inhibitors based upon pharmacophore models derived from the receptor and its ligands. Science China Chemistry
2767 Esposito G, et al. Pivagabine: a novel psychoactive drug. Arzneimittelforschung. 1997 Nov;47(11A):1306-9.
2768 Serra M, et al. Antagonism by pivagabine of stress-induced changes in GABAA receptor function and corticotropin-releasing factor concentrations in rat brain. Psychoneuroendocrinology. 1999 Apr;24(3):269-84.
2769 Junjun Wu, et al. Selective inhibitors of tumor progression loci-2 (Tpl2) kinase with potent inhibition of TNF-alpha production in human whole blood. Bioorg Med Chem Lett. 2009 Jul 1;19(13):3485-8.
2770 Rashid HU, et al. Cyclen-based Gd3+ complexes as MRI contrast agents: Relaxivity enhancement and ligand design. Bioorg Med Chem. 2016 Nov 15;24(22):5663-5684.
2771 Liu WS, et al. Structure based design of selective SHP2 inhibitors by De novo design, synthesis and biological evaluation. J Comput Aided Mol Des. 2019 Aug;33(8):759-774.
2772 Garcia Fortanet J, et al. Allosteric Inhibition of SHP2: Identification of a Potent, Selective, and Orally Efficacious Phosphatase Inhibitor. J Med Chem. 2016 Sep 8;59(17):7773-82.
2773 Aronsen D, et, al. RU 24969-produced adipsia and hyperlocomotion: differential role of 5HT 1A and 5HT 1B receptor mechanisms. Pharmacol Biochem Behav. 2014 Sep; 124: 1-4.
2774 Brazell MP, et, al. The 5-HT1 receptor agonist RU-24969 decreases 5-hydroxytryptamine (5-HT) release and metabolism in the rat frontal cortex in vitro and in vivo. Br J Pharmacol. 1985 Sep; 86(1): 209-16.
2775 Yang Q, et al. Anti-thrombotic effects of α-linolenic acid isolated from Zanthoxylum bungeanum Maxim seeds. BMC Complement Altern Med. 2014 Sep 23;14:348.
2776 Desire L, et al. RAC1 inhibition targets amyloid precursor protein processing by gamma-secretase and decreases Abeta production in vitro and in vivo. J Biol Chem. 2005 Nov 11;280(45):37516-25.
2777 Shutes A, et al. Specificity and mechanism of action of EHT 1864, a novel small molecule inhibitor of Rac family small GTPases. J Biol Chem. 2007 Dec 7;282(49):35666-78.
2778 Onesto C, et al. Characterization of EHT 1864, a novel small molecule inhibitor of Rac family small GTPases. Methods Enzymol. 2008;439:111-29.
2779 Li YJ, et al. Allosteric Inhibition of Ubiquitin-like Modifications by a Class of Inhibitor of SUMO-Activating Enzyme. Cell Chem Biol. 2018 Dec 5. pii: S2451-9456(18)30386-6.
2780 Pacifici GM, et al. Valpromide inhibits human epoxide hydrolase. Br J Clin Pharmacol. 1986 Sep;22(3):269-74.
2781 Gorres KL, et al. Valpromide Inhibits Lytic Cycle Reactivation of Epstein-Barr Virus. MBio. 2016 Mar 1;7(2):e00113.
2782 Nakatani Y, et al. Neuroprotective effect of liquiritin as an antioxidant via an increase in glucose-6-phosphate dehydrogenase expression on B65 neuroblastoma cells. Eur J Pharmacol. 2017 Nov 15;815:381-390.
2783 Zeng C, et al. Liquiritin, as a Natural Inhibitor of AKR1C1, Could Interfere With the Progesterone Metabolism. Front Physiol. 2019 Jul 3;10:833.
2784 Porter RH,et al. Functional characterization of agonists at recombinant human 5-HT2A, 5-HT2B and 5-HT2C receptors in CHO-K1 cells.Br J Pharmacol. 1999 Sep;128(1):13-20.
2785 Jenck F, et al. Antiaversive effects of 5HT2C receptor agonists and fluoxetine in a model of panic-like anxiety in rats.Eur Neuropsychopharmacol. 1998 Aug;8(3):161-8.
2786 Faassen F, et al. Caco-2 permeability, P-glycoprotein transport ratios and brain penetration of heterocyclic drugs.Int J Pharm. 2003 Sep 16;263(1-2):113-22.
2787 Xue X, et al. Discovery of novel inhibitors disrupting HIF-1α/von Hippel-Lindau interaction through shape-based screening and cascade docking. PeerJ. 2016 Dec 15;4:e2757.
2788 Lu J, et al. Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4. Chem Biol. 2015 Jun 18;22(6):755-63.
2789 https://clinicaltrials.gov/ct2/show/NCT04424901?term=DIPYRIDAMOLE&cond=covid&draw=2&rank=1
2790 Xiaowen Chen, et al. Toll-like receptor 4 is involved in a protective effect of rhein on immunoglobulin A nephropathy. Indian J Pharmacol. 2015 Jan-Feb; 47(1): 27–33.
2791 Hou ML, et al. The Drug-Drug Effects of Rhein on the Pharmacokinetics and Pharmacodynamics of Clozapine in Rat Brain Extracellular Fluid by In Vivo Microdialysis. J Pharmacol Exp Ther. 2015 Oct;355(1):125-34.
2792 Yan-Xi Zhou, et al. Rhein: A Review of Pharmacological Activities. Evid Based Complement Alternat Med. 2015; 2015: 578107.
2793 http://en.wikipedia.org/wiki/Temoporfin
2794 Chem. Zentralbl 1912 II:396 (1912)
2795 Gray LR, et al. The NRTIs lamivudine, stavudine and zidovudine have reduced HIV-1 inhibitory activity in astrocytes. PLoS One. 2013 Apr 16;8(4):e62196.
2796 Hou P, et al. Genome editing of CXCR4 by CRISPR/cas9 confers cells resistant to HIV-1 infection. Sci Rep. 2015 Oct 20;5:15577.
2797 Mizutani T, et al. Nucleoside Reverse Transcriptase Inhibitors Suppress Laser-Induced Choroidal Neovascularization in Mice. Invest Ophthalmol Vis Sci. 2015 Nov;56(12):7122-9.
2798 Cheng J, et al. Cyanidin Chloride inhibits ovariectomy-induced osteoporosis by suppressing RANKL-mediated osteoclastogenesis and associated signaling pathways. J Cell Physiol. 2018 Mar;233(3):2502-2512.
2799 Lee SW, et al. Phenolic compounds isolated from Psoralea corylifolia inhibit IL-6-induced STAT3 activation. Planta Med. 2012 Jun;78(9):903-6.
2800 Kim DW, et al. Phenolic phytochemical displaying SARS-CoV papain-like protease inhibition from the seeds of Psoralea corylifolia. J Enzyme Inhib Med Chem. 2014 Feb;29(1):59-63.
2801 Li YG, et al. Fructus Psoraleae contains natural compounds with potent inhibitory effects towards human carboxylesterase 2. Fitoterapia. 2015 Jan 13;101C:99-106. d
2802 J Steroid Biochem Mol Biol 37:257 (1990); Recent Advances Polyphenol Res 1:293 (2008)
2803 Northrup AB, et al, Discovery of 1-[3-(1-methyl-1H-pyrazol-4-yl)-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl]-N-(pyridin-2-ylmethyl)methanesulfonamide (MK-8033): A Specific c-Met/Ron dual kinase inhibitor with preferential affinity for the activated state of c-Met. J Med Chem. 2013 Mar 28;56(6):2294-310.
2804 Bhardwaj V, et al. C-Met inhibitor MK-8003 radiosensitizes c-Met-expressing non-small-cell lung cancer cells with radiation-induced c-Met-expression. J Thorac Oncol. 2012 Aug;7(8):1211-7.
2805 Rosato-Siri MD, et al. A Novel Modulator of Kv3 Potassium Channels Regulates the Firing of Parvalbumin-Positive Cortical Interneurons. J Pharmacol Exp Ther. 2015 Sep;354(3):251-60.
2806 Aust J Chem 19:525 (1966); J Inclusion Phenomena Macrocyclic Chem 72: 339 (2011)
2807 Arch Pharmakol Exp Pathol 268:348 (1971)
2808 Suwannarat, P., et al., Use of nitisinone in patients with alkaptonuria. Metabolism, 2005. 54(6): p. 719-28.
2809 Santra, S. and U. Baumann, Experience of nitisinone for the pharmacological treatment of hereditary tyrosinaemia type 1. Expert Opin Pharmacother, 2008. 9(7): p. 1229-36.
2810 Alexandrou AJ, et al. Subtype-Selective Small Molecule Inhibitors Reveal a Fundamental Role for Nav1.7 in Nociceptor Electrogenesis, Axonal Conduction and Presynaptic Release. PLoS One. 2016 Apr 6;11(4):e0152405.
2811 Theile JW, et al. The Selective Nav1.7 Inhibitor, PF-05089771, Interacts Equivalently with Fast and Slow Inactivated Nav1.7 Channels. Mol Pharmacol. 2016 Nov;90(5):540-548.
2812 Antimicro Agents Chemother 19:56, 20:171 (1981); Arzneim Forsch 33:269 (1983)
2813 Ying Xi, et al. Inhibition of epithelial-to-mesenchymal transition and pulmonary fibrosis by methacycline. Am J Respir Cell Mol Biol. 2014 Jan;50(1):51-60.
2814 https://clinicaltrials.gov/ct2/show/NCT04666753?term=GLUCOSAMINE&cond=covid&draw=2&rank=2
2815 Brueckner B, et al. Epigenetic reactivation of tumor suppressor genes by a novel small-molecule inhibitor of human DNA methyltransferases. Cancer Res. 2005 Jul 15;65(14):6305-11.
2816 Schirrmacher E, et al. Synthesis and in vitro evaluation of biotinylated RG108: a high affinity compound for studying binding interactions with human DNA methyltransferases. Bioconjug Chem. 2006 Mar-Apr;17(2):261-6.
2817 Pasha Z, et al. Efficient non-viral reprogramming of myoblasts to stemness with a single small molecule to generate cardiac progenitor cells. PLoS One. 2011;6(8):e23667.
2818 J Org Chem 30: 1729 (1965); J Biol Chem 279:56053 (2004);
2819 Whittle BJ, et al. Binding and activity of the prostacyclin receptor (IP) agonists, treprostinil and iloprost, at human prostanoid receptors: treprostinil is a potent DP1 and EP2 agonist. Biochem Pharmacol. 2012 Jul 1;84(1):68-75.
2820 Ferrantino M, et al. Inhaled treprostinil sodium for the treatment of pulmonary arterial hypertension. Expert Opin Pharmacother. 2011 Nov;12(16):2583-93.
2821 Ghonem N, et al. Treprostinil, a prostacyclin analog, ameliorates ischemia-reperfusion injury in rat orthotopic liver transplantation. Am J Transplant. 2011 Nov;11(11):2508-16.
2822 Smadja DM, et al. Treprostinil indirectly regulates endothelial colony forming cell angiogenic properties by increasing VEGF-A produced by mesenchymal stem cells. Thromb Haemost. 2015 Oct;114(4):735-47.
2823 Kazemi Z, et al. Repurposing Treprostinil for Enhancing Hematopoietic Progenitor Cell Transplantation. Mol Pharmacol. 2016 Jun;89(6):630-44.
2824 Nikam VS, et al. Treprostinil inhibits the recruitment of bone marrow-derived circulating fibrocytes in chronic hypoxic pulmonary hypertension. Eur Respir J. 2010 Dec;36(6):1302-14.
2825 Napper AD, et al. Discovery of indoles as potent and selective inhibitors of the deacetylase SIRT1. J Med Chem. 2005 Dec 15;48(25):8045-54.
2826 Sadikot T, et al. Development of a high-throughput screening cancer cell-based luciferase refolding assay for identifying Hsp90 inhibitors. Assay Drug Dev Technol. 2013 Oct;11(8):478-88.
2827 Zhu J, et al. Ethoxyquin prevents chemotherapy-induced neurotoxicity via Hsp90 modulation. Ann Neurol. 2013 Dec;74(6):893-904.
2828 Zhu J, et al. Ethoxyquin provides neuroprotection against cisplatin-induced neurotoxicity. Sci Rep. 2016 Jun 28;6:28861.
2829 Milne JC, et al. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature. 2007 Nov 29; 450(7170): 712–716.
2830 Scuto A, et al. SIRT1 activation enhances HDAC inhibition-mediated upregulation of GADD45G by repressing the binding of NF-κB/STAT3 complex to its promoter in malignant lymphoid cells. Cell Death Dis. 2013 May; 4(5): e635.
2831 Gurt I, et al. The Sirt1 Activators SRT2183 and SRT3025 Inhibit RANKL-Induced Osteoclastogenesis in Bone Marrow-Derived Macrophages and Down-Regulate Sirt3 in Sirt1 Null Cells. PLoS One. 2015 Jul 30;10(7):e0134391.
2832 Int J Immunopharmacol 6: 587 (1984); Nucleic Acids Res 25: 1890 (1997)
2833 J Am Pharmac Assoc 29:425 (1940); Food Cosmet Toxicol 5:141 (1967)
2834 Gong Y, et al. Specific expression of proton-coupled oligopeptide transporter 1 in primary hepatocarcinoma-anovel strategy for tumor-targeted therapy. Oncol Lett. 2017 Oct;14(4):4158-4166.
2835 Giustarini G, et al. The hepatotoxic fluoroquinolone trovafloxacin disturbs TNF- and LPS-induced p65 nuclear translocation in vivo and in vitro. Toxicol Appl Pharmacol. 2020 Mar 15;391:114915.
2836 Poon IK, et al. Unexpected link between an antibiotic, pannexin channels and apoptosis. Nature. 2014 Mar 20;507(7492):329-34.
2837 Gootz TD, et al. Activity of the new fluoroquinolone trovafloxacin (CP-99,219) against DNA gyrase and topoisomerase IV mutants of Streptococcus pneumoniae selected in vitro. Antimicrob Agents Chemother. 1996 Dec;40(12):2691-7.
2838 Kim YK, et al. Anticancer effects of CKD-602 (Camtobell?) via G2/M phase arrest in oral squamous cell carcinoma cell lines. Oncol Lett. 2015 Jan;9(1):136-142.
2839 Kim YY, et al. CKD-602, a camptothecin derivative, inhibits proliferation and induces apoptosis in glioma cell lines. Oncol Rep. 2009 Jun;21(6):1413-9.
2840 Kim CY, et al. Antitumor activity of CKD-602, a camptothecin derivative, in a mouse glioma model. J Clin Neurosci. 2012 Feb;19(2):301-5.
2841 Wang Y, et al. Discovery of Biaryl Amides as Potent, Orally Bioavailable, and CNS Penetrant RORγt Inhibitors. ACS Med Chem Lett. 2015 May 26;6(7):787-792.
2842 Morrison BL, et al. Oxyphenisatin acetate (NSC 59687) triggers a cell starvation response leading to autophagy, mitochondrial dysfunction, and autocrine TNFα-mediated apoptosis. Cancer Med. 2013 Oct;2(5):687-700.
2843 Mackman RL, et al. Discovery of an oral respiratory syncytial virus (RSV) fusion inhibitor (GS-5806) and clinical proof of concept in a human RSV challenge study. J Med Chem. 2015 Feb 26;58(4):1630-1643.
2844 Samuel D, et al. GS-5806 inhibits pre- to postfusion conformational changes of the respiratory syncytial virus fusion protein. Antimicrob Agents Chemother. 2015 Nov;59(11):7109-12.
2845 Anderson DL. Doripenem. Drugs Today (Barc). 2006 Jun;42(6):399-404.
2846 Jones RN, et al. Doripenem (S-4661), a novel carbapenem: comparative activity against contemporary pathogens including bactericidal action and preliminary in vitro methods evaluations. J Antimicrob Chemother. 2004 Jul;54(1):144-54. Epub 2004 Jun 9.
2847 Sivaprakasam P, et al. Discovery of new acylaminopyridines as GSK-3 inhibitors by a structure guided in-depth exploration of chemical space around a pyrrolopyridinone core. Bioorg Med Chem Lett. 2015 May 1;25(9):1856-63.
2848 Santiago de Oliveira Y, et al. The design of novel metronidazole benzoate structures: exploring stoichiometric diversity. Acta Crystallogr C Struct Chem. 2019 May 1;75(Pt 5):483-495.
2849 Am J Clin Nutrition 47:660 (1988); Amino Acids 23:381 (2002); Endocrinology 147:3276 (2006)
2850 Anne Marie Jeanne Bouillot, et al. 1, 2, 3-triazole derivatives for use as stearoyl-coa desaturase inhibitors . PCT Int. Appl. (2009), WO 2009060053 A1 20090514.
2851 Chanteux H, et al. Cross-Species Differences in the Preclinical Pharmacokinetics of CT7758, an α4β1/α4β7 Integrin Antagonist. Drug Metab Dispos. 2015 Sep;43(9):1381-91.
2852 Davenport RJ, et al. Alpha4-integrin antagonism--an effective approach for the treatment of inflammatory diseases? Drug Discov Today. 2007 Jul;12(13-14):569-76.
2853 Ind Eng Chem 33: 637 (1941)
2854 Moilanen AM, et al. Discovery of ODM-201, a new-generation androgen receptor inhibitor targeting resistance mechanisms toandrogen signaling-directed prostate cancer therapies. Sci Rep. 2015 Jul 3;5:12007. doi: 10.1038/srep12007.
2855 Edy Meiyanto, et al. Curcumin Analog Pentagamavunon-1 (PGV-1) Sensitizes Widr Cells to 5-Fluorouracil Through Inhibition of NF-κB Activation. Asian Pac J Cancer Prev. 2018 Jan 27;19(1):49-56.
2856 Beni Lestari, et al. Pentagamavunon-1 (PGV-1) Inhibits ROS Metabolic Enzymes and Suppresses Tumor Cell Growth by Inducing M Phase (Prometaphase) Arrest and Cell Senescence. Sci Rep . 2019 Oct 16;9(1):14867.
2857 https://clinicaltrials.gov/ct2/show/NCT04701606?term=Artesunate&cond=COVID-19&draw=2&rank=1 https://clinicaltrials.gov/ct2/show/NCT04387240?term=Artesunate&cond=COVID-19&draw=2&rank=2 https://clinicaltrials.gov/ct2/show/NCT04695197?term=Artesunate&cond=COVID-19&draw=2&rank=3 https://clinicaltrials.gov/ct2/show/NCT04475107?term=Artesunate&cond=COVID-19&draw=2&rank=4 https://clinicaltrials.gov/ct2/show/NCT04532931?term=Artesunate&cond=COVID-19&draw=2&rank=5 https://clinicaltrials.gov/ct2/show/NCT04374019?term=Artesunate&cond=COVID-19&draw=2&rank=6 https://trialsearch.who.int/Trial2.aspx?TrialID=PACTR202006899597082
2858 William AD, et al. Discovery of kinase spectrum selective macrocycle (16E)-14-methyl-20-oxa-5,7,14,26-tetraazatetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8(27),9,11,16,21,23-decaene (SB1317/TG02), a potent inhibitor of cyclin dependent kina
2859 Pasha MK, et al. Preclinical metabolism and pharmacokinetics of SB1317 (TG02), a potent CDK/JAK2/FLT3 inhibitor. Drug Metab Lett. 2012 Mar;6(1):33-42.
2860 Sun CC, et al. PTUPB ameliorates high-fat diet-induced non-alcoholic fatty liver disease via inhibiting NLRP3 inflammasome activation in mice. Biochem Biophys Res Commun. 2020 Mar 19;523(4):1020-1026.
2861 Zhang G, et al. Dual inhibition of cyclooxygenase-2 and soluble epoxide hydrolase synergistically suppresses primary tumor growth and metastasis. Proc Natl Acad Sci U S A. 2014 Jul 29;111(30):11127-32.
2862 Hwang SH, et al. Synthesis and structure-activity relationship studies of urea-containing pyrazoles as dual inhibitors of cyclooxygenase-2 and soluble epoxide hydrolase.J Med Chem. 2011 Apr 28;54(8):3037-50.
2863 Michael J. Chisamore, et al. Identification of Small Molecule Estrogen-Related
2864 Chen G, et al. Cell Synchronization by Double Thymidine Block. Bio Protoc. 2018 Sep 5;8(17).
2865 FIRKET H, et al. Autoradiographic visualization of synthesis of deoxyribonucleic acid in tissue culture with tritium-labelled thymidine. Nature. 1958 Jan 24;181(4604):274-5.FIRKET H, et al. Autoradiographic visualization of synthesis of deoxyribonucleic acid in tissue culture with tritium-labelled thymidine. Nature. 1958 Jan 24;181(4604):274-5.
2866 Izeradjene K, et al. Inhibition of thymidine synthesis by folate analogues induces a Fas-Fas ligand-independentdeletion of superantigen-reactive peripheral T cells. Int Immunol. 2001 Jan;13(1):85-93.
2867 Nacht M, et al. Discovery of a potent and isoform-selective targeted covalent inhibitor of the lipid kinase PI3Kα. J Med Chem. 2013 Feb 14;56(3):712-21.
2868 Mol Pharmacol 3:274 (1967); Ann Intern Med 72:919 (1970); 73:607 (1970)
2869 Mégalizzi V, et al. 4-IBP, a sigma1 receptor agonist, decreases the migration of human cancer cells, including glioblastoma cells, in vitro and sensitizes them in vitro and in vivo to cytotoxic insults of proapoptotic and proautophagic drugs. Neoplasia. 2007 May;9(5):358-69.
2870 Pestic Sci 6:537 (1975); 8:264 (1977); Arch Toxicol 67:510 (1993)
2871 Liang ZZ, et al. Oligofurostanosides from Asparagus cochinchinensis. Planta Med. 1988 Aug;54(4):344-6.
2872 Gai Y, et al. Pseudoprotodioscin inhibits SREBPs and microRNA 33a/b levels and reduces the gene expression regarding the synthesis of cholesterol and triglycerides. Fitoterapia. 2019 Nov;139:104393.
2873 Forsyth T, et al. SAR and in vivo evaluation of 4-aryl-2-aminoalkylpyrimidines as potent and selective Janus kinase 2 (JAK2) inhibitors. Bioorg Med Chem Lett. 2012 Dec 15;22(24):7653-8.
2874 Yonar D, et al. Effect of cis-(Z)-flupentixol on DPPC membranes in the presence and absence of cholesterol. Chem Phys Lipids. 2016 Jun;198:61-71.
2875 Kim MJ, et al. Loganin protects against pancreatitis by inhibiting NF-κB activation. Eur J Pharmacol. 2015 Oct 15;765:541-50.
2876 Tsai WH, et al. Ba-Wei-Di-Huang-Wan through its active ingredient loganin counteracts substance P-enhanced NF-κB/ICAM-1 signaling in rats with bladder hyperactivity. Neurourol Urodyn. 2015 Aug 19.
2877 Survey Anesthesiology 12:377 (1968); Acta Physiol Scand 141:289 (1991)
2878 Lejeune, P., et al. (2015) Abstract 3524: BAY 1238097, a novel BET inhibitor with strong efficacy in hematological tumor models. Cancer Research, 75(15 Suppl), 884.
2879 Bernasconi E, et al. Preclinical evaluation of the BET bromodomain inhibitor BAY 1238097 for the treatment of lymphoma. Br J Haematol. 2017 Sep;178(6):936-948.
2880 Clin Perinatol 11:703 (1984)
2881 Panpan Wu, et al. Phytochemical Compositions of Extract From Peel of Hawthorn Fruit, and Its Antioxidant Capacity, Cell Growth Inhibition, and Acetylcholinesterase Inhibitory Activity. BMC Complement Altern Med. 2017 Mar 11;17(1):151.
2882 J Am Pharm Assoc Sci Ed 45:382 (1956); Toxicol Appl Pharmacol 18:185 (1971)
2883 Shima, Fumi, et al. In silico discovery of small-molecule Ras inhibitors that display antitumor activity by blocking the Ras-effector interaction. Proceedings of the National Academy of Sciences of the United States of America (2013), 110(20), 8182-8187, S8182/1-S8182/10.
2884 Wurz RP, et al. A "Click Chemistry Platform" for the Rapid Synthesis of Bispecific Molecules for Inducing Protein Degradation. J Med Chem. 2018 Jan 25;61(2):453-461.
2885 https://clinicaltrials.gov/ct2/show/NCT04467931?term=ETHACRYNIC+ACID&cond=Covid19&draw=2&rank=1
2886 Chem Commun 1965: 302
2887 Campbell DR, et al. Flavonoid inhibition of aromatase enzyme activity in human preadipocytes. J Steroid Biochem Mol Biol. 1993 Sep;46(3):381-8.
2888 McGinn R et al. Adenosine receptor inhibition attenuates the suppression of postexercise cutaneous blood flow. J Physiol. 2014 Jun 15;592(12):2667-78.
2889 Tew GA et al. Aging and aerobic fitness affect the contribution of noradrenergic sympathetic nerves to the rapid cutaneous vasodilator response to local heating.&#x0D; J Appl Physiol (1985). 2011 May;110(5):1264-70
2890 Cakir B et al.Leptin inhibits gastric emptying in rats: role of CCK receptors and vagal afferent fibers. Physiol Res. 2007;56(3):315-22. Epub 2006 Jun 22.
2891 Matthew et al. Structure-Based Drug Discovery of MRTX1257, a Selective, Covalent KRAS G12C Inhibitor with Oral Activity in Animal Models of Cancer.
2892 Toque HA, et al. Pharmacological characterization of a novel phosphodiesterase type 5 (PDE5) inhibitor lodenafil carbonate on human and rabbit corpus cavernosum. Eur J Pharmacol. 2008 Sep 4;591(1-3):189-95.
2893 Khajista Jabeen, et al. Antifungal Compounds From Melia Azedarach Leaves for Management of Ascochyta Rabiei, the Cause of Chickpea Blight. Nat Prod Res. 2011 Feb;25(3):264-76.
2894 Rivera JC, et al. Tetrahydrobiopterin (BH4) deficiency is associated with augmented inflammation and microvascular degeneration in the retina. J Neuroinflammation. 2017 Sep 6;14(1):181.
2895 Lefranc F, et al. Narciclasine, a plant growth modulator, activates Rho and stress fibers in glioblastoma cells. Mol Cancer Ther. 2009 Jul;8(7):1739-50.
2896 Wahyuni DS, et al. The use of bio-guided fractionation to explore the use of leftover biomass in Dutch flower bulb production as allelochemicals against weeds. Molecules. 2013 Apr 17;18(4):4510-25.
2897 Arch Pathol Lab Med 100:127 (1976); J Pediatr Surg 18:131 (1983)
2898 Saporito MS, et al. MLR-1023 is a potent and selective allosteric activator of Lyn kinase in vitro that improves glucose tolerance in vivo. J Pharmacol Exp Ther. 2012 Jul;342(1):15-22.
2899 Ochman AR, et al. The Lyn kinase activator MLR-1023 is a novel insulin receptor potentiator that elicits a rapid-onset and durable improvement in glucose homeostasis in animal models of type 2 diabetes. J Pharmacol Exp Ther. 2012 Jul;342(1):23-32.
2900 PNAS 585: (1964); Gene 62:121 (1988); FEBS Letts 234:141 (1988); Kidney Internat 62:496 (2002)
2901 Nadezhda German, et al. Deconstruction of the α4β2 Nicotinic Acetylchloine (nACh) Receptor Positive Allosteric Modulator des-Formylflustrabromine (dFBr). J Med Chem. 2011 Oct 27;54(20):7259-67.
2902 Weltzin MM, et al. Desformylflustrabromine Modulates α4β2 Neuronal Nicotinic Acetylcholine Receptor High- and Low-Sensitivity Isoforms at Allosteric Clefts Containing the β2 Subunit. J Pharmacol Exp Ther. 2015 Aug;354(2):184-94.
2903 T Honoré, et al. Quinoxalinediones: Potent Competitive non-NMDA Glutamate Receptor Antagonists. Science. 1988 Aug 5;241(4866):701-3.
2904 Neuman RS, et al. Blockade of excitatory synaptic transmission by 6-cyano-7-nitroquinoxaline-2,3-dione(CNQX) in the hippocampus in vitro. Neurosci Lett. 1988 Sep 23;92(1):64-8.
2905 Alford S, et al. CNQX and DNQX block non-NMDA synaptic transmission but not NMDA-evoked locomotion in lamprey spinal cord. Brain Res. 1990 Jan 8;506(2):297-302.
2906 Pia Bäckström, et al. Attenuation of Cocaine-Seeking Behaviour by the AMPA/kainate Receptor Antagonist CNQX in Rats. Psychopharmacology (Berl). 2003 Feb;166(1):69-76.
2907 Kim M, et al. Infusion of the non-NMDA receptor antagonist CNQX into the amygdala blocks the expression of fear-potentiated startle. Behav Neural Biol. 1993 Jan;59(1):5-8.
2908 Therapie 22:309 (1967); Food Chem Toxicol 37:789 (1999)
2909 Pan Q, et al. Inhibition of the angiogenesis and growth of Aloin in human colorectal cancer in vitro and in vivo. Cancer Cell Int. 2013 Jul 12;13(1):69.
2910 Tabolacci C, et al. Aloin enhances cisplatin antineoplastic activity in B16-F10 melanoma cells by transglutaminase-induced differentiation. Amino Acids. 2013 Jan;44(1):293-300.
2911 Cui Y, et al. Aloin protects against chronic alcoholic liver injury via attenuating lipid accumulation, oxidative stress and inflammation in mice. Arch Pharm Res. 2014 Dec;37(12):1624-33. |J Chem Soc 1932: 2573
2912 Parasitol. Today (2000), 16(2), 71-77; Am. J. Trop. Med. Hyg. (1974), 23(2), 151-3; Parasitology (1975), 70(2), 273-85|
2913 Liu C, et al. In vivo and in vitro efficacies of mebendazole, mefloquine and nitazoxanide against cyst echinococcosis. Parasitol Res. 2015 Mar 15.
2914 Pawluk SA, et al. A review of pharmacokinetic drug-drug interactions with the anthelmintic medications albendazole and mebendazole. Clin Pharmacokinet. 2015 Apr;54(4):371-83.
2915 Speich B, et al. Efficacy and safety of albendazole plus ivermectin, albendazole plus mebendazole, albendazole plus oxantel pamoate, and mebendazole alone against Trichuris trichiura and concomitant soil-transmitted helminth infections: a four-arm, randomised controlled trial. Lancet Infect Dis. 2015 Mar;15(3):277-84.
2916 Larsen AR, et al. Repurposing the antihelmintic mebendazole as a hedgehog inhibitor. Mol Cancer Ther. 2015 Jan;14(1):3-13.
2917 JACS 79: 149 (1957)
2918 Kong M, et al. Effects of polyphyllin I on growth inhibition of human non-small lung cancer cells and in xenograft. Acta Biochim Biophys Sin (Shanghai). 2010 Nov;42(11):827-33.
2919 Liu J, et al. Polyphyllin I induces G2/M phase arrest and apoptosis in U251 human glioma cells via mitochondrial dysfunction and the JNK signaling pathway. Acta Biochim Biophys Sin (Shanghai). 2017 Jun 1;49(6):479-486.
2920 He J, et al. Polyphyllin I induces autophagy and cell cycle arrest via inhibiting PDK1/Akt/mTOR signal and downregulating cyclin B1 in human gastric carcinoma HGC-27 cells. Biomed Pharmacother. 2019 Sep;117:109189.
2921 Han X, et al. Discovery of RG7834: The First-in-Class Selective and Orally Available Small Molecule Hepatitis B Virus Expression Inhibitor with Novel Mechanism of Action. J Med Chem. 2018 Oct 4.
2922 Koo CY, et al. Targeting TAO Kinases Using a New Inhibitor Compound Delays Mitosis and Induces Mitotic Cell Death in Centrosome Amplified Breast Cancer Cells. Mol Cancer Ther. 2017 Nov;16(11):2410-2421.
2923 Crawford TD, et al. Discovery of a Potent and Selective in Vivo Probe (GNE-272) for the Bromodomains of CBP/EP300. J Med Chem. 2016 Dec 8;59(23):10549-10563.
2924 Infect. Dis. Ther. (1994), 9, 391-401; J. Antimicrob. Chemother. (1976), 2(4), 325-36; J. Pharm. Pharmacol. (1964), 16, 663-9|
2925 Jiang X, et al. A novel application of furazolidone: anti-leukemic activity in acute myeloid leukemia. PLoS One. 2013 Aug 9;8(8):e72335.
2926 Khadrawy YA, et al. Cerebellar neurochemical and histopathological changes in rat model of Parkinson's disease induced by intrastriatal injection of rotenone. Gen Physiol Biophys. 2016 Nov 30.
2927 Guan Q, et al. RNA-Seq Expression Analysis of Enteric Neuron Cells with Rotenone Treatment and Prediction of Regulated Pathways. Neurochem Res. 2016 Nov 30.
2928 Kishore Kumar SN, et al. Morinda citrifolia mitigates rotenone-induced striatal neuronal loss in male Sprague-Dawley rats by preventing mitochondrial pathway of intrinsic apoptosis. Redox Rep. 2016 Nov 24:1-12.
2929 Zhang ZN, et al. Subcutaneous rotenone rat model of Parkinson's disease: dose exploration study. Brain Res. 2016 Nov 19. pii: S0006-8993(16)30776-4.
2930 Li N, et al. Mitochondrial complex I inhibitor rotenone induces apoptosis through enhancing mitochondrial reactive oxygen species production. J Biol Chem. 2003 Mar 7;278(10):8516-25. |Chem Rev 12: 181 (1933); Prog Chem Org Nat Prod 43: 1 (1983)
2931 Meyer SC, et al. CHZ868, a Type II JAK2 Inhibitor, Reverses Type I JAK Inhibitor Persistence and Demonstrates Efficacy in Myeloproliferative Neoplasms. Cancer Cell. 2015 Jul 13;28(1):15-28.
2932 Wu SC, et al. Activity of the Type II JAK2 Inhibitor CHZ868 in B Cell Acute Lymphoblastic Leukemia. Cancer Cell. 2015 Jul 13;28(1):29-41.
2933 Walters MJ, et al. Characterization of CCX282-B, an orally bioavailable antagonist of the CCR9 chemokine receptor, for treatment of inflammatory bowel disease. J Pharmacol Exp Ther. 2010 Oct;335(1):61-9.
2934 Bekker P, et al. CCR9 Antagonists in the Treatment of Ulcerative Colitis. Mediators Inflamm. 2015;2015:628340.
2935 Zhang J, et al. Biarylsulfonamide CCR9 inhibitors for inflammatory bowel disease. Bioorg Med Chem Lett. 2015 Sep 1;25(17):3661-4.
2936 Brown JH, et al. Activation and blockade of cardiac muscarinic receptors by endogenous acetylcholine and cholinesterase inhibitors. J Pharmacol Exp Ther. 1982 Oct;223(1):20-4.
2937 Gum GG, et al. Effect of topically applied demecarium bromide and echothiophate iodide on intraocular pressure and pupil size in beagles with normotensive eyes and beagles with inherited glaucoma. Am J Vet Res. 1993 Feb;54(2):287-93.
2938 Yang H, et al. Celastrol, a triterpene extracted from the Chinese "Thunder of God Vine," is a potent proteasome inhibitor and suppresses human prostate cancer growth in nude mice. Cancer Res. 2006 May 1;66(9):4758-65
2939 Guan Y, et al. Celastrol attenuates oxidative stress in the skeletal muscle of diabetic rats by regulating the AMPK-PGC1α-SIRT3 signaling pathway. Int J Mol Med. 2016 May;37(5):1229-38. |J Chem Soc 1963:2884; 1972:330; J Org Chem 30:1729 (1965); J Biol Chem 279:56053 (2004); J Mol Med 85:1421 (2007); Mol Biol Cell 19:1104 (2008)
2940 Mahoney E, et al. ER stress and autophagy: new discoveries in the mechanism of action and drug resistance of the cyclin-dependent kinase inhibitor flavopiridol.Blood. 2012 Aug 9;120(6):1262-1273.
2941 Keskin H, et al. Complex effects of flavopiridol on the expression of primary response genes. Cell Div. 2012 Mar 29;7:11.
2942 Kim KS, et al.Thio- and oxoflavopiridols, cyclin-dependent kinase 1-selective inhibitors: synthesis and biological effects. J Med Chem. 2000 Nov 2;43(22):4126-34.
2943 Jianliang Xu, et al. Inhibition of cyclin E1 sensitizes hepatocellular carcinoma cells to regorafenib by mcl-1 suppression. Cell Commun Signal. 2019 Jul 26;17(1):85.
2944 Ber 74:1851 (1941); J Chem Soc (C) 1967:145 ; Pharmaceut Biol 43:647 (2005)
2945 Hibasami H, et al. Induction of apoptosis by rhapontin having stilbene moiety, a component of rhubarb (&lt;i&gt;Rheum officinale Baillon&lt;/i&gt;) in human stomach cancer KATO III cells. Oncol Rep. 2007 Aug;18(2):347-51.
2946 Rorick-Kehn LM, et al. A Novel, Orally Bioavailable Nociceptin Receptor Antagonist, LY2940094, Reduces Ethanol Self-Administration and Ethanol Seeking in Animal Models. Alcohol Clin Exp Res. 2016 May;40(5):945-54.
2947 https://trialsearch.who.int/Trial2.aspx?TrialID=NCT04923347
2948 Connie L. Erickson-Miller, et al. GSK626616: A DYRK3 Inhibitor as a Potential New Therapy for the Treatment of Anemia. Blood 2007 110:510;
2949 Wippich F, et al. Dual specificity kinase DYRK3 couples stress granule condensation/dissolution to mTORC1 signaling. Cell. 2013;152(4):791-805.
2950 Mirguet O, et al. Discovery of epigenetic regulator I-BET762: lead optimization to afford a clinical candidate inhibitor of the BET bromodomains. J Med Chem. 2013 Oct 10;56(19):7501-15.
2951 Hauck S, et al. Pyrazolo[1,5a]pyrimidines as a new class of FUSE binding protein 1 (FUBP1) inhibitors. Bioorg Med Chem. 2016 Nov 15;24(22):5717-5729.
2952 Antimicrob Agents Chemother 49:4649 (2005); J Biol Chem 282:25395 (2007)
2953 Maziah M, et al. The Production of 9-methoxycanthin-6-one from Callus Cultures of (Eurycoma longifolia Jack) Tongkat Ali. Methods Mol Biol. 2009;547:359-69.
2954 Tripetch Kanchanapoom , et al. Canthin-6-one and b-carboline alkaloids from Eurycoma harmandiana. Phytochemistry 56 (2001) 383-386.
2955 Slusarczyk M, et al. Application of ProTide technology to gemcitabine: a successful approach to overcome the key cancer resistance mechanisms leads to a new agent (NUC-1031) in clinical development. J Med Chem. 2014 Feb 27;57(4):1531-42.
2956 Choi SS, et al. Antinociceptive mechanisms of orally administered decursinol in the mouse. Life Sci. 2003 Jun 13;73(4):471-85.
2957 Son SH, et al. Decursin and decursinol from Angelica gigas inhibit the lung metastasis of murine colon carcinoma. Phytother Res. 2011 Jul;25(7):959-64.
2958 J Chem Soc 1954:1171; Atherosclerosis 50:73 (1984)
2959 Naurex's First Orally Active Molecule, NRX-1074, Demonstrates Statistically Significant Improvement in Depression Scores within 24 Hours in Phase 2 Study for Major Depressive Disorder. January 28, 2015.
2960 J Pharmacol Exp Ther 63:369 (1938); Anal Profiles Drug Subs 6:423 (1977)
2961 J. Allergy and Clin. Immunol. (1981), 68(2), 91-7; Eur. J. Pharmacol. (1970), 12(1), 35-43; Arzneim. Forsch. (1967), 17(3), 362-4
2962 Tröster A, et al. NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. ChemMedChem. 2018 Aug 20;13(16):1629-1633.
2963 Pharmazie (1957), 12, 396-401; Monatsh. Chem. (1957), 88, 330-5.
2964 Chem Nat Comp 1: 59 (1962)
2965 J Clin Psychiatry 43:1 (1982); Drugs 32:114 (1986); Pharmacotherapy 8:100 (1988)
2966 C R SeancesSoc Biol Ses Fil 152:1371 (1958); Can Psychiatr Assoc J 14:267 (1969); Br J Clin Pract 42:228 (1988)
2967 Durant ST, et al. The brain-penetrant clinical ATM inhibitor AZD1390 radiosensitizes and improves survival of preclinical brain tumor models. Sci Adv. 2018 Jun 20;4(6):eaat1719.
2968 J. Kahn, et al. Next-Generation ATM Kinase Inhibitors Under Development Radiosensitize Glioblastoma With Conformal Radiation in a Mouse Orthotopic Model. IJROBP. 2017. 99, 600-601.
2969 Willson TM, et al. The PPARs: from orphan receptors to drug discovery. J Med Chem. 2000 Feb 24;43(4):527-50.
2970 Fujita M, et al. In vitro and in vivo cytotoxicity of troglitazone in pancreatic cancer. J Exp Clin Cancer Res. 2017 Jul 3;36(1):91.
2971 Nazim UM, et al. PPARγ activation by troglitazone enhances human lung cancer cells to TRAIL-induced apoptosis via autophagy flux. Oncotarget. 2017 Apr 18;8(16):26819-26831.
2972 Arzneim Forsch 20:1024 (1970); S Afr Med J 58:444 (1980)
2973 Roymans D, et al. Therapeutic efficacy of a respiratory syncytial virus fusion inhibitor. Nat Commun. 2017 Aug 1;8(1):167.
2974 Kim JW, et al. Telbivudine: a novel nucleoside analog for chronic hepatitis B. Ann Pharmacother. 2006;40(3):472-478.
2975 Zobel T, et al. Telbivudine Reduces Parvovirus B19-Induced Apoptosis in Circulating Angiogenic Cells. Viruses. 2019;11(3):227. Published 2019 Mar 6.
2976 Smyth JT, et al. Inhibition of the inositol trisphosphate receptor of mouse eggs and A7r5 cells by KN-93 via a mechanism unrelated to Ca2+/calmodulin-dependent protein kinase II antagonism. J Biol Chem. 2002;277(38):35061-35070.
2977 An P, et al. KN-93, a specific inhibitor of CaMKII inhibits human hepatic stellate cell proliferation in vitro. World J Gastroenterol. 2007;13(9):1445-1448.
2978 https://clinicaltrials.gov/ct2/show/NCT04365127?term=Progesterone&cond=COVID-19&draw=2&rank=1 https://clinicaltrials.gov/ct2/show/NCT04865029?term=Progesterone&cond=COVID-19&draw=2&rank=2
2979 Galili N, et al. Prediction of response to therapy with ezatiostat in lower risk myelodysplastic syndrome. J Hematol Oncol. 2012 May 6;5:20
2980 Ruscoe JE, et al. Pharmacologic or genetic manipulation of glutathione S-transferase P1-1 (GSTpi) influences cell proliferation pathways. J Pharmacol Exp Ther. 2001 Jul;298(1):339-45.
2981 Boskovic ZV, ET AL. Inhibition of Zinc-Dependent Histone Deacetylases with a Chemically Triggered Electrophile. ACS Chem Biol. 2016 Jul 15;11(7):1844-51.
2982 Eur. J. Pharmacol. (1977), 42(4), 347-54; J. Pharm. Sci. (1968), 57(5), 774-80
2983 Mitchell JD, et al. In vitro pharmacodynamics of gamithromycin against Mycoplasma mycoides subspecies mycoides Small Colony. Vet J. 2013 Sep;197(3):806-11.
2984 F. Hildebrand, et al. Efficacy of Gamithromycin for the Treatment of Foals with Mild to Moderate Bronchopneumonia. J Vet Intern Med. 2015 Jan-Feb; 29(1): 333–338.
2985 Ikenoya M, et al. A selective ACAT-1 inhibitor, K-604, suppresses fatty streak lesions in fat-fed hamsters without affecting plasma cholesterol levels. Atherosclerosis. 2007 Apr;191(2):290-7.
2986 Shibuya Y, et al. Acyl-coenzyme A:cholesterol acyltransferase 1 blockage enhances autophagy in the neurons of triple transgenic Alzheimer's disease mouse and reduces human P301L-tau content at the presymptomatic stage. Neurobiol Aging. 2015 Jul;36(7):2248-2259.
2987 J. Drugs Dermatol. (2011), 10(11), 1282-1288; Antimicrob. Agents Chemother. (1981), 19(3), 386-9; Antimicrob. Agents Chemother. (1981), 19(3), 390-2
2988 J Am Coll Toxicol 3:147 (1984); Clin Chim Acta 224:147 (1994); J Appl Toxicol 23:285 (2003)
2989 Brai A, et al. Human DDX3 protein is a valuable target to develop broad spectrum antiviral agents. Proc Natl Acad Sci U S A. 2016 May 10;113(19):5388-93.
2990 Lelais G, et al. Discovery of (R,E)-N-(7-Chloro-1-(1-[4-(dimethylamino)but-2-enoyl]azepan-3-yl)-1H-benzo[d]imidazol-2-yl)-2-methylisonicotinamide (EGF816), a Novel, Potent, and WT Sparing Covalent Inhibitor of Oncogenic (L858R, ex19del) and Resistant (T79
2991 Jia Y, et al. EGF816 Exerts Anticancer Effects in Non-Small Cell Lung Cancer by Irreversibly and Selectively Targeting Primary and Acquired Activating Mutations in the EGF Receptor. Cancer Res. 2016 Mar 15;76(6):1591-602
2992 Dooley KL, et al. Comparative carcinogenicity of the food pyrolysis product, 2-amino-5-phenylpyridine, and the known human carcinogen, 4-aminobiphenyl, in the neonatal B6C3F1 mouse. Cancer Lett. 1988 Jul;41(1):99-103.
2993 Stavenuiter JF, et al. Syntheses of 5-phenyl-2-pyridinamine, a possibly carcinogenic pyrolysis product of phenylalanine, and some of its putative metabolites. Carcinogenesis. 1985 Jan;6(1):13-9.
2994 Linda N. Casillas, et al. Prodrugs of amino quinazoline kinase inhibitor. PCT Int. Appl. (2014), WO 2014043446 A1 20140320.
2995 Wilson JD, et al. Azatadine maleate (Zadine): evaluation in the management of allergic rhinitis. N Z Med J. 1981 Aug 12;94(689):79-81.
2996 Tozzi S, et al. The pharmacology of azatadine, a potential antiallergy drug. Agents Actions. 1974 Oct;4(4):264-70.
2997 Wang B, Chen L, Zhen H, et al. Proteomic changes induced by podophyllotoxin in human cervical carcinoma HeLa cells. Am J Chin Med. 2013;41(1):163-75.
2998 Guerrero E, Abad A, Montenegro G, et al. Analgesic and anti-inflammatory activity of podophyllotoxin derivatives. Pharm Biol. 2013 Jan 31.
2999 Li M, Zhou L, Yang D, et al. Biochemical composition and antioxidant capacity of extracts from Podophyllum hexandrum rhizome. BMC Complement Altern Med. 2012 Dec 22;12:263.
3000 Prasad V, Chaudhuri AR, Curcio M, et al. Podophyllotoxin and nocodazole counter the effect of IKP104 on tubulin decay. J Protein Chem. 1998 Oct;17(7):663-8.
3001 Podophyllotoxin |JACS 73: 2909 (1951); 75: 1308 (1953); J Med Chem 32: 604 (1989); Pharmacol Ther 59: 163 (1993); J Prot Chem 17: 663 (1998)
3002 Romero FA, et al. GNE-781, A Highly Advanced Potent and Selective Bromodomain Inhibitor of Cyclic Adenosine Monophosphate Response Element Binding Protein, Binding Protein (CBP). J Med Chem. 2017 Nov 22;60(22):9162-9183.
3003 Niu Q, et al. Structure-guided drug design identifies a BRD4-selective small molecule that suppresses HIV. J Clin Invest. 2019 Jul 22;129(8):3361-3373.
3004 Vansant G, et al. Block-And-Lock Strategies to Cure HIV Infection. Viruses. 2020 Jan 10;12(1). pii: E84.
3005 Brasier AR, et al. Validation of the epigenetic reader bromodomain-containing protein 4 (BRD4) as a therapeutic target for treatment of airway remodeling. Drug Discov Today. 2020 Jan;25(1):126-132.
3006 Clin Obster Gynacol 11:573 (1984)
3007 O'Neil MM, et al. Differential Regulation of Gonadotropins in Response to Continuous Infusion of Native Gonadotropin-Releasing Hormone in the Winter Anovulatory Mare and Effects of Treatment With Estradiol-17β. J Equine Vet Sci. 2019 Apr;75:93-103.
3008 J Chem Soc 1960:3827; Chem Commun 1970:1388
3009 J Org Chem 30: 1729 (1965)
3010 J Chem Soc 1961: 3705; Phytochemistry 10: 1845 (1971)
3011 Jones P, et al. Discovery of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): a novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors. J Med Chem. 2009 Nov 26;52(22):7170-85.
3012 Bridges KA, et al. Niraparib (MK-4827), a novel poly(ADP-Ribose) polymerase inhibitor, radiosensitizes human lung and breast cancer cells. Oncotarget. 2014 Jul 15;5(13):5076-86.
3013 Wang L, et al. MK-4827, a PARP-1/-2 inhibitor, strongly enhances response of human lung and breast cancer xenografts to radiation. Invest New Drugs. 2012 Dec;30(6):2113-20.
3014 Mirza MR, et al. Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer. N Engl J Med. 2016 Dec 1;375(22):2154-2164.
3015 Vashi P, et al. Methylmalonic Acid and Homocysteine as Indicators of Vitamin B-12 Deficiency in Cancer. PLoS One. 2016 Jan 25;11(1):e0147843.
3016 Plantevin Krenitsky V, et al. Discovery of CC-930, an orally active anti-fibrotic JNK inhibitor. Bioorg Med Chem Lett. 2012 Feb 1;22(3):1433-8.
3017 Gan LT, et al. Hepatocyte free cholesterol lipotoxicity results from JNK1-mediated mitochondrial injury and is HMGB1 and TLR4-dependent. J Hepatol. 2014 Dec;61(6):1376-84.
3018 Reich N, et al. Jun N-terminal kinase as a potential molecular target for prevention and treatment of dermal fibrosis. Ann Rheum Dis. 2012 May;71(5):737-45.
3019 Tavernier SJ, et al. Regulated IRE1-dependent mRNA decay sets the threshold for dendritic cell survival. Nat Cell Biol. 2017 Jun;19(6):698-710.
3020 van der Horst G, et al. Targeting of α(v)-integrins in stem/progenitor cells and supportive microenvironment impairs bone metastasis in human prostate cancer. Neoplasia. 2011 Jun;13(6):516-25.
3021 Reeves KJ, et al. Prostate cancer cells home to bone using a novel in vivo model: modulation by the integrin antagonist GLPG0187. Int J Cancer. 2015 Apr 1;136(7):1731-40.
3022 https://clinicaltrials.gov/ct2/show/NCT04350593?term=Dapagliflozin&cond=COVID-19&draw=2&rank=1 https://clinicaltrials.gov/ct2/show/NCT04393246?term=Dapagliflozin&cond=COVID-19&draw=2&rank=2 https://trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2020/09/027829 https://trialsearch.who.int/Trial2.aspx?TrialID=NCT04595370 https://trialsearch.who.int/Trial2.aspx?TrialID=NCT04724837
3023 JACS 74: 4365 (1952); J Pharmacol Exp Therap 116: 394 (1956)
3024 Keystone Symposia 2019 - Epigenetics and Human Disease
3025 Kati W, et al. In vitro activity and resistance profile of dasabuvir, a nonnucleoside hepatitis C virus polymerase inhibitor. Antimicrob Agents Chemother. 2015 Mar;59(3):1505-11.
3026 Wood M, et al. Rotigotine is a potent agonist at dopamine D1 receptors as well as at dopamine D2 and D3 receptors. Br J Pharmacol. 2015 Feb;172(4):1124-35.
3027 Scheller D, et al. The in vitro receptor profile of rotigotine: a new agent for the treatment of Parkinson's disease. Naunyn Schmiedebergs Arch Pharmacol. 2009 Jan;379(1):73-86.
3028 Fenu S, et al. In vivo dopamine agonist properties of rotigotine: Role of D1 and D2 receptors. Eur J Pharmacol. 2016 Oct 5;788:183-91.
3029 Radad K, et al. Neuroprotective effect of rotigotine against complex I inhibitors, MPP+ and rotenone, in primary mesencephalic cell culture. Folia Neuropathol. 2014;52(2):179-86.
3030 Ayman N Saber, et al. Dissipation Dynamic, Residue Distribution and Processing Factor of Hexythiazox in Strawberry Fruits Under Open Field Condition. Food Chem. 2016 Apr 1;196:1108-16.
3031 R Nauen, et al. Acaricide Toxicity and Resistance in Larvae of Different Strains of Tetranychus Urticae and Panonychus Ulmi (Acari: Tetranychidae). Pest Manag Sci. 2001 Mar;57(3):253-61.
3032 https://clinicaltrials.gov/ct2/show/NCT04542213?term=Linagliptin&cond=Covid19&draw=2&rank=1
3033 Cheng H et al. Discovery of the Highly Potent PI3K/mTOR Dual Inhibitor PF-04979064 through Structure-Based Drug Design. ACS Med Chem Lett, 2012 Nov 7, 4(1):91-7.
3034 Hideshima T, et al. Discovery of selective small-molecule HDAC6 inhibitor for overcoming proteasome inhibitor resistance in multiple myeloma. Proc Natl Acad Sci U S A. 2016 Nov 15;113(46):13162-13167.
3035 Liang M, et al. Identification and characterization of a potent, selective, and orally active antagonist of the CC chemokine receptor-1. J Biol Chem. 2000 Jun 23;275(25):19000-8.
3036 Anders HJ, et al. A chemokine receptor CCR-1 antagonist reduces renal fibrosis after unilateral ureter ligation. J Clin Invest. 2002 Jan;109(2):251-9.
3037 Furuichi K, et al. Chemokine receptor CCR1 regulates inflammatory cell infiltration after renal ischemia-reperfusion injury. J Immunol. 2008 Dec 15;181(12):8670-6.
3038 Horuk R, et al. A non-peptide functional antagonist of the CCR1 chemokine receptor is effective in rat heart transplant rejection. J Biol Chem. 2001 Feb 9;276(6):4199-204.
3039 https://clinicaltrials.gov/ct2/show/NCT04467931?term=NISOLDIPINE&cond=Covid19&draw=2&rank=1
3040 Clin Exp Dermatol 17 Suppl 1:1 (1992); Drugs 49:103 (1995)
3041 Hejmadi MV, et al. DNA damage following combination of radiation with the bioreductive drug AQ4N: possible selective toxicity to oxic and hypoxic tumour cells. Br J Cancer. 1996 Feb;73(4):499-505.
3042 Manley E Jr, et al. Impact of tumor blood flow modulation on tumor sensitivity to the bioreductive drug banoxantrone. J Pharmacol Exp Ther. 2013 Feb;344(2):368-77.
3043 Williams KJ, et al. In vivo activation of the hypoxia-targeted cytotoxin AQ4N in human tumor xenografts. Mol Cancer Ther. 2009 Dec;8(12):3266-75.
3044 Shin D, et al. Nrf2 inhibition reverses resistance to GPX4 inhibitor-induced ferroptosis in head and neck cancer. Free Radic Biol Med. 2018 Dec;129:454-462.
3045 Heinemann B, et al. Inhibition of demethylases by GSK-J1/J4. Nature. 2014 Oct 2;514(7520):E1-2
3046 Carta M, et al. The muscle relaxant thiocolchicoside is an antagonist of GAB&lt;sub&gt;A&lt;/sub&gt;A receptor function in the central nervous system. Neuropharmacology. 2006 Sep;51(4):805-15.
3047 Br J Ophthalmol 66:386 (1982); 79:42 (1995)|
3048 Elia, A.C., et al., Transferability of oxytetracycline (OTC) from feed to carp muscle and evaluation of the antibiotic effects on antioxidant systems in liver and kidney. Fish Physiol Biochem, 2014.
3049 Pickens LB, et al. Oxytetracycline biosynthesis. J Biol Chem. 2010 Sep 3;285(36):27509-15.
3050 Oguz Guvenmez, et al. A New Treatment Method for Herpes Simplex Virus Type 1-related Skin Lesions. Scientific &amp; Academic. 2019; 8(1): 6-8.
3051 J Pharm Sci 73:1657 (1984); Clin Ther 3:80 (1980); 6:388 (1984); Curr Ther Res 42:720 (1987)
3052 Cross BC, et al. The molecular basis for selective inhibition of unconventional mRNA splicing by an IRE1-binding small molecule. Proc Natl Acad Sci U S A. 2012 Apr 10;109(15):E869-78.
3053 Zhang L, et al. IRE1 inhibition perturbs the unfolded protein response in a pancreatic β-cell line expressing mutant proinsulin, but does not sensitize the cells to apoptosis. BMC Cell Biol. 2014 Jul 10;15:29.
3054 Kemp K, et al. The serine-threonine kinase inositol-requiring enzyme 1α (IRE1α) promotes IL-4 production in T helper cells. J Biol Chem. 2013 Nov 15;288(46):33272-82.
3055 Tufanli O, et al. Targeting IRE1 with small molecules counteracts progression of atherosclerosis. Proc Natl Acad Sci U S A. 2017 Feb 21;114(8):E1395-E1404.
3056 Nam ST, et al. Suppression of IgE-mediated mast cell activation and mouse anaphylaxis via inhibition of Sykactivation by 8-formyl-7-hydroxy-4-methylcoumarin, 4μ8C. Toxicol Appl Pharmacol. 2017 Oct 1;332:25-31.
3057 https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=PREGNENOLONE+&cntry=&state=&city=&dist=&Search=Search
3058 Wess J, et al. Novel designer receptors to probe GPCR signaling and physiology. Trends Pharmacol Sci. 2013 Jul;34(7):385-92.
3059 Silva RR, et al. Evaluation of Functional Selectivity of NSC 170973, Clozapine, and LASSBio-579, an Experimental Compound With Antipsychotic-Like Actions in Rodents, at G Protein and Arrestin Signaling Downstream of the Dopamine D2 Receptor. Front Pharmacol. 2019 Jun 4;10:628.
3060 Zorn SH, et al. Clozapine is a potent and selective muscarinic M4 receptor agonist. Eur J Pharmacol. 1994 Nov 15;269(3):R1-2.
3061 Manvich DF, et al. The DREADD agonist clozapine N-oxide (CNO) is reverse-metabolized to clozapine and produces clozapine-like interoceptive stimulus effects in rats and mice. Sci Rep. 2018 Mar 1;8(1):3840.
3062 van der Peet PL, et al. Gram scale preparation of clozapine N-oxide (CNO), a synthetic small molecule actuator for muscarinic acetylcholine DREADDs. MethodsX. 2018 Mar 23;5:257-267.
3063 Joseph Cichon, et al. Branch-specific dendritic Ca(2+) spikes cause persistent synaptic plasticity. Nature. 2015 Apr 9;520(7546):180-5.
3064 Scott D Ryan, et al. Heterogeneity in the sn-1 carbon chain of platelet-activating factor glycerophospholipids determines pro- or anti-apoptotic signaling in primary neurons. J Lipid Res. 2008 Oct;49(10):2250-8.
3065 Z Honda, et al. Transfected platelet-activating factor receptor activates mitogen-activated protein (MAP) kinase and MAP kinase kinase in Chinese hamster ovary cells. J Biol Chem. 1994 Jan 21;269(3):2307-15.
3066 Muhammad S Riaz, et al. Direct Growth Inhibitory Effect of Platelet Activating Factor C-16 and Its Structural Analogs on Mycobacteria. Front Microbiol. 2018 Sep 11;9:1903.
3067 Jing Chu, et al. IGHG1 Regulates Prostate Cancer Growth via the MEK/ERK/c-Myc Pathway. Biomed Res Int. 2019 Jul 4;2019:7201562.
3068 Nina Bögershausen, et al. RAP1-mediated MEK/ERK pathway defects in Kabuki syndrome. J Clin Invest. 2015 Sep;125(9):3585-99.
3069 Liles JT, et al. ASK1 contributes to fibrosis and dysfunction in models of kidney disease. J Clin Invest. 2018 Oct 1;128(10):4485-4500.
3070 Budas GR, et al. ASK1 Inhibition Halts Disease Progression in Preclinical Models of Pulmonary Arterial Hypertension. Am J Respir Crit Care Med. 2018 Feb 1;197(3):373-385.
3071 Lee YH, et al. Baccatin III, a precursor for the semisynthesis of paclitaxel, inhibits the accumulation and suppressive activity of myeloid-derived suppressor cells in tumor-bearing mice. Int Immunopharmacol. 2014 Aug;21(2):487-93.
3072 Jaren W Landen, et al. Noscapine Crosses the Blood-Brain Barrier and Inhibits Glioblastoma Growth. Clin Cancer Res. 2004 Aug 1;10(15):5187-201.
3073 Yunfan Yang, et al. CYLD Regulates Noscapine Activity in Acute Lymphoblastic Leukemia via a Microtubule-Dependent Mechanism. Theranostics. 2015 Mar 2;5(7):656-66.
3074 Vartika Tomar, et al. Noscapine and Its Analogs as Chemotherapeutic Agent: Current Updates. Curr Top Med Chem. 2017;17(2):174-188.
3075 Bianca Lokhorst, et al. Interaction of OTC Drug Noscapine and Acenocoumarol and Phenprocoumon. Br J Clin Pharmacol. 2019 May;85(5):1041-1043.
3076 S A Ebrahimi, et al. Interaction of Noscapine With the Bradykinin Mediation of the Cough Response. Acta Physiol Hung. 2003;90(2):147-55.
3077 Avelar MM, et al. Procyanidin b2 cytotoxicity to mcf-7 human breast adenocarcinoma cells. Indian J Pharm Sci. 2012 Jul;74(4):351-5.
3078 Yang H, et al. Procyanidin B2 inhibits NLRP3 inflammasome activation in human vascular endothelial cells. Biochem Pharmacol. 2014 Dec 15;92(4):599-606.
3079 Wu S, et al. Procyanidin B2 attenuates neurological deficits and blood-brain barrier disruption in a rat model of cerebral ischemia. Mol Nutr Food Res. 2015 Oct;59(10):1930-41.
3080 Tamura M, et al. Development of specific Rho-kinase inhibitors and their clinical application. Biochim Biophys Acta. 2005 Dec 30;1754(1-2):245-52. Epub 2005 Sep 12.
3081 Ikenoya M, et al. Inhibition of rho-kinase-induced myristoylated alanine-rich C kinase substrate (MARCKS) phosphorylation in human neuronal cells by H-1152, a novel and specific Rho-kinase inhibitor. J Neurochem. 2002 Apr;81(1):9-16.
3082 Lie M, et al. Accelerated neurite growth from spiral ganglion neurons exposed to the Rho kinase inhibitor H-1152. Neuroscience. 2010 Aug 25;169(2):855-62.
3083 Expert Opin. Pharmacother. (2000), 1(4), 835-840; Eur. J. Clin. Pharmacol. (1979), 16(6), 423-4; Arzneim. Forsch. (1976), 26(12), 2145-54
3084 https://clinicaltrials.gov/ct2/show/NCT04509973?term=Betamethasone&cond=Covid19&draw=2&rank=1 https://clinicaltrials.gov/ct2/show/NCT04649879?term=Betamethasone&cond=Covid19&draw=2&rank=2 https://clinicaltrials.gov/ct2/show/NCT04412291?term=Betamethasone&cond=Covid19&draw=2&rank=3 https://clinicaltrials.gov/ct2/show/NCT04462367?term=Betamethasone&cond=Covid19&draw=2&rank=4https://trialsearch.who.int/Trial2.aspx?TrialID=NCT04734210 https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20210311050671N1
3085 Kwiatkowski N, et al. Small-molecule kinase inhibitors provide insight into Mps1 cell cycle function. Nat Chem Biol. 2010 May;6(5):359-68.
3086 Bäumer W , et al. The selective glucocorticoid receptor agonist mapracorat displays a favourable safety-efficacy ratio for the topical treatment of inflammatory skin diseases in dogs. Vet Dermatol. 2017 Feb; 28(1):46-e11.
3087 Ber 18: 79, 1928 (1885); J Pharmacol Exp Ther 104:20 (1952)
3088 Doyle K, et al. Discovery of Second Generation Reversible Covalent DPP1 Inhibitors Leading to an Oxazepane Amidoacetonitrile Based Clinical Candidate (AZD7986). J Med Chem. 2016 Oct 27;59(20):9457-9472.
3089 Tetrahedron 25:2233 (1969); J Pharmacy Pharmacol 54:399 (2002); J Ethnopharmacol 81:111 (2002)
3090 Vet Dermatol 16:299 (2005); J Vet Pharmacol Ther 30:257 (2007)
3091 Ferreira de Freitas R, et al. Discovery of a Potent and Selective Coactivator Associated Arginine Methyltransferase 1 (CARM1) Inhibitor by Virtual Screening. J Med Chem. 2016 Jul 28;59(14):6838-47.
3092 Takaya J, et al. A Potent and Site-Selective Agonist of TRPA1. J Am Chem Soc. 2015 Dec 23;137(50):15859-64.
3093 Compt Rend 109:29 (1889); JACS 82:125 (1960)
3094 Nature 384:39 (1996)
3095 J Nutr 108:1215 (1978); Food Chemical Toxicol 47:2723 (2009)
3096 Proffitt KD, et al. Pharmacological inhibition of the Wnt acyltransferase PORCN prevents growth of WNT-driven mammary cancer. Cancer Res. 2013 Jan 15;73(2):502-7.
3097 Cheng Y, et al. Wnt-C59 arrests stemness and suppresses growth of nasopharyngeal carcinoma in mice by inhibiting the Wnt pathway in the tumor microenvironment. Oncotarget. 2015 Jun 10;6(16):14428-39.
3098 Shetty HU, et al. Cerebrospinal fluid and plasma distribution of myo-inositol and other polyols in Alzheimer disease. Clin Chem. 1996 Feb;42(2):298-302.
3099 Arch Surg 118:1431 (1983); Liver International 6:35 (1986)
3100 Dang L, et al. Effects of hypocrellin A on expression of vascular endothelial growth factor and endothelin-1 in human umbilical endothelial cells. Am J Chin Med. 2007;35(4):713-23.
3101 Ma YJ, et al. Enhanced Production of Hypocrellin A in Submerged Cultures of Shiraia bambusicola by Red Light. Photochem Photobiol. 2019 May;95(3):812-822.
3102 Fehr MJ, et al. Roles of oxygen and photoinduced acidification in the light-dependent antiviral activity of hypocrellin A. Biochemistry. 1995 Dec 5;34(48):15845-8.
3103 Ma G, et al. Antimicrobial and antileishmanial activities of hypocrellins A and B. Antimicrob Agents Chemother. 2004 Nov;48(11):4450-2.
3104 Ng YF, et al. Semen Astragali Complanati: an ethnopharmacological, phytochemical and pharmacological review. J Ethnopharmacol. 2014 Aug 8;155(1):39-53.
3105 Ng YF, et al. Semen Astragali Complanati: an ethnopharmacological, phytochemical and pharmacological review. J Ethnopharmacol. 2014 Aug 8;155(1):39-53.
3106 Mol. Aspects Med. (2010), 31(6), 513-539; J. Food Biochem. (2005), 29(3), 234-266; Cell. Mol. Targets Chemoprev. (1992), 147-60.
3107 Gullino PM, et al. N-nitrosomethylurea as mammary gland carcinogen in rats. J Natl Cancer Inst. 1975 Feb;54(2):401-14.
3108 Tsubura A, et al. Review: Animal models of N-Methyl-N-nitrosourea-induced mammary cancer and retinal degeneration with special emphasis on therapeutic trials. In Vivo. 2011 Jan-Feb;25(1):11-22.
3109 Johnson EM, et al. Effects of N-nitroso-N-methylurea on enzymatic ontogeny associated with teratogenesis. Teratology. 1968 May;1(2):179-91.
3110 Silvia Garbarino, et al. One-pot synthesis of α-haloketones employing a membrane-based semibatch diazomethane generator. Journal of Flow Chemistry volume 6, pages211-217(2016).
3111 Moon KY. N-nitroso-N-methylurea and N-nitroso-N-ethylurea induce upregulation of cellular NF-kappa B activity through protein kinase C-dependent pathway in human malignant keratinocytes. Arch Pharm Res. 2010 Jan;33(1):133-9.
3112 DeWeerd K, et al. Metabolism of the 18O-methoxy substituent of 3-methoxybenzoic acid and other unlabeled methoxybenzoic acids by anaerobic bacteria. Appl Environ Microbiol. 1988 May;54(5):1237-42.
3113 Fulcher, Emilee H, et al. Method for the treatment and prevention of the inflammatory diseases using Rho kinase inhibiting compounds. US 20090325960 A1.
3114 Yu WN, et al. Citronellol Induces Necroptosis of Human Lung Cancer Cells via TNF-α Pathway and Reactive Oxygen Species Accumulation. In Vivo. 2019 Jul-Aug;33(4):1193-1201
3115 Grimm C, et al. Small molecule activators of TRPML3. Chem Biol. 2010 Feb 26;17(2):135-48.
3116 Zhiqiang Xia, et al. ML-SA1, a selective TRPML agonist, inhibits DENV2 and ZIKV by promoting lysosomal acidification and protease activity. Antiviral Res. 2020 Aug 26;104922.
3117 https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=RETINYL+PALMITATE&cntry=&state=&city=&dist=&Search=Search
3118 Hatcher JM, et al. Discovery of a Pyrrolopyrimidine (JH-II-127), a Highly Potent, Selective, and Brain Penetrant LRRK2 Inhibitor. ACS Med Chem Lett. 2015 Apr 7;6(5):584-589.
3119 Girnita A, et al. Cyclolignans as inhibitors of the insulin-like growth factor-1 receptor and malignant cell growth. Cancer Res. 2004 Jan 1;64(1):236-42.
3120 Menu E, et al. Inhibiting the IGF-1 receptor tyrosine kinase with the cyclolignan PPP: an in vitro and in vivo study in the 5T33MM mouse model. Blood. 2006 Jan 15;107(2):655-60. Epub 2005 Jul 26.
3121 Bieghs L, et al. The IGF-1 receptor inhibitor picropodophyllin potentiates the anti-myeloma activity of a BH3-mimetic. Oncotarget. 2014 Nov 30;5(22):11193-208.
3122 Tomizawa M, et al. Picropodophyllin and sorafenib synergistically suppress the proliferation and motility of hepatocellular carcinoma cells. Oncol Lett. 2014 Nov;8(5):2023-2026. Epub 2014 Aug 27.
3123 Stromberg T, et al. IGF-1 receptor tyrosine kinase inhibition by the cyclolignan PPP induces G2/M-phase accumulation and apoptosis in multiple myeloma cells. Blood. 2006 Jan 15;107(2):669-78. Epub 2005 Sep 15.
3124 Kong YL, et al. Insulin deficiency induces rat renal mesangial cell dysfunction via activation of IGF-1/IGF-1R pathway. Acta Pharmacol Sin. 2016 Feb;37(2):217-27. |JACS 73: 2909 (1951); 75: 1308 (1953); J Med Chem 32: 604 (1989); Pharmacol Ther 59: 163 (1993); Cancer Res 64:236 (2004); Int. J. Cancer 121:1857 (2007)
3125 Sadler BM, Stein DS. Clinical pharmacology and pharmacokinetics of amprenavir. Ann Pharmacother. 2002 Jan;36(1):102-18.
3126 Esposito V, Verdina A, Manente L, Amprenavir inhibits the migration in human hepatocarcinoma cell and the growth of xenografts. J Cell Physiol. 2013 Mar;228(3):640-5.
3127 Helsley RN, Sui Y, Ai N, Pregnane X Receptor Mediates Dyslipidemia Induced by the HIV Protease Inhibitor Amprenavir in Mice. Mol Pharmacol. 2013 Jun;83(6):1190-9.
3128 Psychopharmacology 127:73 (1996);132:296 (1997);159:266 (2002); Br J Psychiatry 175:120 (1999)
3129 Chen W, et al. Camphor--a fumigant during the Black Death and a coveted fragrant wood in ancient Egypt and Babylon--a review. Molecules. 2013 May 10;18(5):5434-54.
3130 Obstetrics Gynecol 17:90 (1961)
3131 Lavorini F, et al. Antitussive effect of carcainium chloride in patients with chronic cough and idiopathic interstitial pneumonias: A pilot study. Pulm Pharmacol Ther. 2016 Oct;40:91-4.
3132 Adcock JJ, et al. RSD931, a novel anti-tussive agent acting on airway sensory nerves. Br J Pharmacol. 2003 Feb;138(3):407-16.
3133 Abdelraheem WH, et al. Degradation and mineralization of organic UV absorber compound 2-phenylbenzimidazole-5-sulfonic acid (PBSA) using UV-254nm/H2O2. J Hazard Mater. 2015 Jan 23;282:233-40.
3134 Ronan B, et al. A highly potent and selective Vps34 inhibitor alters vesicle trafficking and autophagy. Nat Chem Biol. 2014 Dec;10(12):1013-9.
3135 Pasquier B. SAR405, a PIK3C3/Vps34 inhibitor that prevents autophagy and synergizes with MTOR inhibition in tumor cells. Autophagy. 2015 Apr 3;11(4):725-6.
3136 Hildebrand JM, et al. Activation of the pseudokinase MLKL unleashes the four-helix bundle domain to induce membrane localization and necroptotic cell death. Proc Natl Acad Sci U S A. 2014 Oct 21;111(42):15072-7.
3137 Sammond DM, et al. Discovery of a novel and potent series of dianilinopyrimidineurea and urea isostere inhibitors of VEGFR2 tyrosine kinase. Bioorg Med Chem Lett. 2005;15(15):3519-3523.
3138 Nachbur U, et al. A RIPK2 inhibitor delays NOD signalling events yet prevents inflammatory cytokine production. Nat Commun. 2015 Mar 17;6:6442.
3139 Guzik K, et al. Small-Molecule Inhibitors of the Programmed Cell Death-1/Programmed Death-Ligand 1 (PD-1/PD-L1) Interaction via Transiently Induced Protein States and Dimerization of PD-L1. J Med Chem. 2017 Jul 13;60(13):5857-5867.
3140 Skalniak L, et al. Small-molecule inhibitors of PD-1/PD-L1 immune checkpoint alleviate the PD-L1-induced exhaustion of T-cells. Oncotarget. 2017 Aug 7;8(42):72167-72181.
3141 Dong Q, et al. Discovery of TAK-733, a potent and selective MEK allosteric site inhibitor for the treatment of cancer. Bioorg Med Chem Lett. 2011 Mar 1;21(5):1315-9.
3142 Micel LN, et al. Antitumor activity of the MEK inhibitor TAK-733 against melanoma cell lines and patient-derived tumor explants. Mol Cancer Ther. 2015 Feb;14(2):317-25.
3143 Wang Y, et al. CDK7-Dependent Transcriptional Addiction in Triple-Negative Breast Cancer. Cell. 2015 Sep 24;163(1):174-186.
3144 Rao DN, et al. A comparative study of the redox-cycling of a quinone (rifamycin S) and a quinonimine (rifabutin) antibiotic by rat liver microsomes. Free Radic Biol Med. 1997;22(3):439-46.
3145 Kono Y. Oxygen Enhancement of bactericidal activity of rifamycin SV on Escherichia coli and aerobic oxidation of rifamycin SV to rifamycin S catalyzed by manganous ions: the role of superoxide. J Biochem. 1982 Jan;91(1):381-95.
3146 Huang H, et al. Rifamycin S and its geometric isomer produced by a newly found actinomycete, Micromonospora rifamycinica. Antonie Van Leeuwenhoek. 2009 Feb;95(2):143-8.
3147 Dominick Casalena, et al. Discovery of small molecule probe that shows anti-tubercular activity via &lt;i&gt;Mtb&lt;/i&gt;bioA (DAPA synthase) enzyme inhibition. January 16, 2015.
3148 PLoS One
3149 Palmer BD, et al. 4-Phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione inhibitors of the checkpoint kinase Wee1. Structure-activity relationships for chromophore modification and phenyl ring substitution. J Med Chem. 2006 Aug 10;49(16):4896-911.
3150 Feng L, et al. Discovery of a Small-Molecule BMP Sensitizer for Human Embryonic Stem Cell Differentiation. Cell Rep. 2016 May 31;15(9):2063-75.
3151 Smaill JB, et al. Synthesis and structure-activity relationships of N-6 substituted analogues of 9-hydroxy-4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones as inhibitors of Wee1 and Chk1 checkpointkinases. Eur J Med Chem. 2008 Jun;43(6):1276-96. Epub 2007 Aug 6.
3152 Wang S, et al. Small-molecule modulation of Wnt signaling via modulating the Axin-LRP5/6 interaction. Nat Chem Biol. 2013 Sep;9(9):579-85.
3153 Fischer G, et al. Ro 25-6981, a highly potent and selective blocker of N-methyl-D-aspartate receptors containing the NR2B subunit. Characterization in vitro. J Pharmacol Exp Ther. 1997 Dec;283(3):1285-92.
3154 Lynch DR, et al. Pharmacological characterization of interactions of RO 25-6981 with the NR2B (epsilon2) subunit. Eur J Pharmacol. 2001 Mar 30;416(3):185-95.
3155 Jiang M, et al. Antinociception and prevention of hyperalgesia by intrathecal administration of Ro 25-6981, a highly selective antagonist of the 2B subunit of N-methyl-D-aspartate receptor. Pharmacol Biochem Behav. 2013 Nov;112:56-63.
3156 J Pharmacol Exp Ther 99:57 (1950)
3157 Schnute ME, et al. Modulation of cellular S1P levels with a novel, potent and specific inhibitor of sphingosine kinase-1. Biochem J. 2012 May 15;444(1):79-88.
3158 MacRitchie N, et al. Effect of the sphingosine kinase 1 selective inhibitor, PF-543 on arterial and cardiac remodelling in a hypoxic model of pulmonary arterial hypertension. Cell Signal. 2016 Aug;28(8):946-55.
3159 Hamada M, et al. Induction of autophagy by sphingosine kinase 1 inhibitor PF-543 in head and neck squamous cell carcinoma cells. Cell Death Discov. 2017 Aug 14;3:17047.
3160 Brit J Ophthal 40:751 (1956); J Pharmacol Exp Ther 121:63 (1957)
3161 Ross-Macdonald P, et al. Identification of a nonkinase target mediating cytotoxicity of novel kinase inhibitors. Mol Cancer Ther. 2008 Nov;7(11):3490-8.
3162 Romarowski A, et al. PKA-dependent phosphorylation of LIMK1 and Cofilin is essential for mouse sperm acrosomal exocytosis. Dev Biol. 2015 Sep 15;405(2):237-49.
3163 Pharmacol Biochem Behav 32:607 (1989); Lancet 1:1014 (1985); CNS Drugs 19:445, 517 (2005)
3164 Kalin JH, et al. Targeting the CoREST complex with dual histone deacetylase and demethylase inhibitors. Nat Commun. 2018 Jan 4;9(1):53.
3165 CR Seances Acad Sci Ser D 271:730 (1970); Antibiotics 3:34 (1975)
3166 J. Colloid Interface Sci. (1971), 37(2), 469-75; Gut (1985), 26(10), 1008-13; Gastroenterology (1985), 89(3), 489-93
3167 Cerchietti LC, et al. A small-molecule inhibitor of BCL6 kills DLBCL cells in vitro and in vivo. Cancer Cell. 2010 Apr 13;17(4):400-11.
3168 https://clinicaltrials.gov/ct2/show/NCT04459286?term=Atazanavir&cond=Covid19&draw=2&rank=1 https://clinicaltrials.gov/ct2/show/NCT04452565?term=Atazanavir&cond=Covid19&draw=2&rank=2 https://clinicaltrials.gov/ct2/show/NCT04468087?term=Atazanavir&cond=Covid19&draw=2&rank=3 https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20210214050350N1 https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20200328046886N2
3169 Hu W, et al. Dihydroartemisinin induces autophagy by suppressing NF-κB activation. Cancer Lett. 2014 Feb 28;343(2):239-48.
3170 Li YJ, et al. Dihydroartemisinin accentuates the anti-tumor effects of photodynamic therapy via inactivation of NF-κB in Eca109 and Ec9706 esophageal cancer cells. Cell Physiol Biochem. 2014;33(5):1527-36.
3171 Li HJ, et al. Dihydroartemisinin-praziquantel combinations and multiple doses of dihydroartemisinin in the treatment of Schistosoma japonicum in experimentally infected mice. Ann Trop Med Parasitol. 2011 Jun;105(4):329-33.
3172 Yap TA, et al. AT13148 is a novel, oral multi-AGC kinase inhibitor with potent pharmacodynamic and antitumor activity. Clin Cancer Res. 2012 Jul 15;18(14):3912-23.
3173 Xi Y, et al. AT13148, a first-in-class multi-AGC kinase inhibitor, potently inhibits gastric cancer cells both in vitro and in vivo. Biochem Biophys Res Commun. 2016 Sep 9;478(1):330-6
3174 Favata MF, et al. Identification of a novel inhibitor of mitogen-activated protein kinase kinase. J Biol Chem. 1998 Jul 17;273(29):18623-32.
3175 Droebner K, et al. Antiviral activity of the MEK-inhibitor U0126 against pandemic H1N1v and highly pathogenic avian influenza virus in vitro and in vivo. Antiviral Res. 2011, 92(2), 195-203.
3176 Bessard A, et al. RNAi-mediated ERK2 knockdown inhibits growth of tumor cells in vitro and in vivo. Oncogene. 2008 Sep 11;27(40):5315-25.
3177 Ahnstedt H, et al. U0126 attenuates cerebral vasoconstriction and improves long-term neurologic outcome after stroke in female rats. J Cereb Blood Flow Metab. 2015 Mar;35(3):454-60.
3178 Fray MJ, et al. Discovery of potent and selective succinyl hydroxamate inhibitors of matrix metalloprotease-3 (stromelysin-1). Bioorg Med Chem Lett. 2001 Feb 26;11(4):571-4.
3179 Yan HQ, et al. Ataxia-telangiectasia mutated activation mediates tumor necrosis factor-alpha induced MMP-13 up-regulation and metastasis in lung cancer cells. Oncotarget. 2016 Sep 20;7(38):62070-62083.
3180 Hafez S, et al. Matrix Metalloprotease 3 Exacerbates Hemorrhagic Transformation and Worsens Functional Outcomes in Hyperglycemic Stroke. Stroke. 2016 Mar;47(3):843-51.
3181 Huang Q, et al. Characterization of the interactions of potent allosteric inhibitors with glutaminase C, a key enzyme in cancer cell glutamine metabolism. J Biol Chem. 2018 Mar 9;293(10):3535-3545.
3182 Chen H, et al. Identification and characterization of small molecules as potent and specific EPAC2 antagonists. J Med Chem. 2013 Feb 14;56(3):952-62.
3183 Wang H, et al. Dual-Targeting Small-Molecule Inhibitors of the Staphylococcus aureus FMN Riboswitch DisruptRiboflavin Homeostasis in an Infectious Setting. Cell Chem Biol. 2017 May 18;24(5):576-588.
3184 Howe JA, et al. Selective small-molecule inhibition of an RNA structural element. Nature. 2015 Oct 29;526(7575):672-7.
3185 Bhatia SP, et al. Fragrance material review on benzyl cinnamate. Food Chem Toxicol. 2007;45 Suppl 1:S40-8. Epub 2007 Sep 14.
3186 Biochem Biophys Res Commun 88: 1382 (1979)
3187 Kategaya L, et al. USP7 small-molecule inhibitors interfere with ubiquitin binding. Nature. 2017 Oct 26;550(7677):534-538.
3188 Phung-Ba V et al. Interaction of pristinamycin IA with P-glycoprotein in human intestinal epithelial cells. Eur J Pharmacol. 1995 Jan 16;288(2):187-92.
3189 https://clinicaltrials.gov/ct2/show/NCT04973449?term=Sucrose&cond=Covid19&draw=2&rank=1 https://trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2020/08/027005 https://trialsearch.who.int/Trial2.aspx?TrialID=SLCTR/2021/008
3190 Beaufils F, et al. 5-(4,6-Dimorpholino-1,3,5-triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine (PQR309), a Potent, Brain-Penetrant, Orally Bioavailable, Pan-Class I PI3K/mTOR Inhibitor as Clinical Candidate in Oncology. J Med Chem. 2017 Sep 14;60(17):7524-7538.
3191 Wicki A, et al. First-in human, phase 1, dose-escalation pharmacokinetic and pharmacodynamic study of the oral dual PI3K and mTORC1/2 inhibitor PQR309 in patients with advanced solid tumors (SAKK 67/13). Eur J Cancer. 2018 Jun;96:6-16.
3192 Drugs (1987), 34(6), 648-61; J. Med. Chem. (1970), 13(4), 684-8; J. Med. Chem. (1973), 16(5), 585-8
3193 You L, et al. Development of a triazole class of highly potent Porcn inhibitors. Bioorg Med Chem Lett. 2016 Dec 15;26(24):5891-5895.
3194 Drugs (1991), 42(6), 1018-60; Antimicrob. Agents Chemother. (1988), 32(5), 656-62; Antimicrob. Agents Chemother. (1987), 31(6), 854-9
3195 Eliseeva EV, et al. Effect of Hypotensive Drugs on Dynamics of Nitroxide-Producing Renal Function in Rats with Nephrogenic Hypertension. Bull Exp Biol Med. 2017 Jan;162(3):357-361.
3196 19-Hydroxybaccatin III, 10-deacetylcephalomannine, and 10-deacetyltaxol: new antitumor taxanes from Taxus wallichiana. J Nat Prod. 1981 May-Jun;44(3):312-9.
3197 Michel Colin, et al. Process for the preparation of taxol and 10-deacetyltaxol. US4857653A.
3198 Helson L. Cephalomannine and 10-deacetyltaxol cytotoxicity in human glial and neuroblastoma cell-lines. Int J Oncol. 1993 Feb;2(2):297-9.
3199 Eur J Clin Pharmacol 19:149 (1981); Int J Pharmaceutics 38:139 (1987)
3200 Nature 174: 930 (1974)
3201 Wolf S, et al. Acute effect of metipranolol on the retinal circulation. Br J Ophthalmol. 1998 Aug;82(8):892-6.
3202 Muzalevskaya EN, et al. SQUALENE: PHYSIOLOGICAL AND PHARMACOLOGICAL PROPERTIES. Eksp Klin Farmakol. 2015;78(6):30-6.
3203 E Gnamusch, et al. Effect of squalene on the structure and function of fungal membranes. Journal of Dermatological Treatment. Volume 3, 1992 - Issue sup1
3204 Ebrahim HY, et al. Usnic Acid Benzylidene Analogues as Potent Mechanistic Target of Rapamycin Inhibitors for the Control of Breast Malignancies. J Nat Prod. 2017 Apr 28;80(4):932-952.
3205 Francolini I, et al. Usnic acid, a natural antimicrobial agent able to inhibit bacterial biofilm formation on polymer surfaces. Antimicrob Agents Chemother. 2004;48(11):4360-4365.
3206 J Chem Soc 1954:2012; Brit J Pharmacol 18:311 (1962); Experientia 30:1308 (1974)
3207 Ameeramja J, et al. Protocatechuic acid methyl ester ameliorates fluoride toxicity in A549 cells. Food Chem Toxicol. 2017 Nov;109(Pt 2):941-950.
3208 Ameeramja J, et al. Protocatechuic acid methyl ester modulates fluoride induced pulmonary toxicity in rats. Food Chem Toxicol. 2018 Aug;118:235-244.
3209 Xia CF, et al. [(18)F]T807, a novel tau positron emission tomography imaging agent for Alzheimer's disease. Alzheimers Dement. 2013 Nov;9(6):666-76.
3210 Marquié M, et al. Validating novel tau positron emission tomography tracer [F-18]-AV-1451 (T807) on postmortem brain tissue. Ann Neurol. 2015 Nov;78(5):787-800.
3211 Dvorak CA, et al. Identification and SAR of Glycine Benzamides as Potent Agonists for the GPR139 Receptor. ACS Med Chem Lett. 2015 Jul 20;6(9):1015-8.
3212 Liu C, et al. GPR139, an Orphan Receptor Highly Enriched in the Habenula and Septum, Is Activated by the Essential Amino Acids L-Tryptophan and L-Phenylalanine. Mol Pharmacol. 2015 Nov;88(5):911-25.
3213 J. Am. Chem. Soc. (1960), 82, 1132-5; Clin. Pharmacol. Ther. (1963), 4, 740-8; Curr. Ther. Res. (1963), 5, 401-6
3214 Prog. Neuro-Psychopharmacol. Biol. Psychiatry (1988), 12(5), 629-37; Arzneim. Forsch. (1982), 32(8), 824-31; Agressologie (1972), 13(5), 285-9
3215 Gardner B, et al. Agonist action at D2(long) dopamine receptors: ligand binding and functional assays. Br J Pharmacol. 1998 Jul;124(5):978-84.
3216 Renodon A, et al. Bromocriptine is a strong inhibitor of brain nitric oxide synthase: possible consequences for the origin of its therapeutic effects.FEBS Lett. 1997 Apr 7;406(1-2):33-6.
3217 Wynalda MA, et al. Assessment of potential interactions between dopamine receptor agonists and various human cytochrome P450 enzymes using a simple in vitro inhibition screen. Drug Metab Dispos. 1997 Oct;25(10):1211-4.
3218 Rana DG, et al. Dopamine mediated antidepressant effect of Mucuna pruriens seeds in various experimental models of depression. Ayu. 2014 Jan;35(1):90-7.
3219 Dieb W, et al. Nigrostriatal dopaminergic depletion increases static orofacial allodynia. J Headache Pain. 2016;17:11.
3220 Yao S, et al. Small Molecule Inhibition of CPS1 Activity through an Allosteric Pocket. Cell Chem Biol. 2020 Mar 19;27(3):259-268.
3221 Jing H, et al. Abrogation of Akt signaling by Isobavachalcone contributes to its anti-proliferative effects towards human cancer cells. Cancer Lett. 2010 Aug 28;294(2):167-77.
3222 Rohatgi N, et al. Novel insulin sensitizer modulates nutrient sensing pathways and maintains β-cell phenotype in human islets. PLoS One. 2013 May 1;8(5):e62012.
3223 Ghosh A, et al. Mitochondrial pyruvate carrier regulates autophagy, inflammation, and neurodegeneration inexperimental models of Parkinson's disease. Sci Transl Med. 2016 Dec 7;8(368):368ra174.
3224 Munro DD, et al. Clobetasone butyrate, a new topical corticosteroid: clinical activity and effects on pituitary-adrenal axis function and model of epidermal atrophy.
3225 Michael Stewart, et al. Clobetasone butyrate for inflammatory skin conditions.
3226 Antiepileptic Drugs (1972), 275-81; Med. Welt (1978), 29(22), 919-26, ; Med. Press (1948), 220(5), 95-7,
3227 Hollister LE, et al. Acetophenazine and diazepam in anxious depressions. Arch Gen Psychiatry. 1971 Mar;24(3):273-8.
3228 Biochem J 36:113 (1942); J Chem Edu 46:198 (1971)
3229 Ferguson FM, et al. Discovery of a selective inhibitor of doublecortin like kinase 1. Nat Chem Biol. 2020 Apr 6.
3230 Cancer Res 48:5941 (1988); Carcinogenesis 27:1803 (2006); 30:321 (2009)
3231 Yasuno F, et al. Increased binding of peripheral benzodiazepine receptor in mild cognitive impairment-dementia converters measured by positron emission tomography with [11C]DAA1106. Psychiatry Res. 2012 Jul 30;203(1):67-74.
3232 DAA1106
3233 Regueiro-Ren A, et al. Synthesis and biological activity of novel epothilone aziridines. Org Lett. 2001 Aug 23;3(17):2693-6.
3234 Pagano A, et al.&#x0D; Epothilone B inhibits migration of glioblastoma cells by inducing microtubule catastrophes and affecting EB1 accumulation at microtubule plus ends.&#x0D; Biochem Pharmacol. 2012 Aug 15;84(4):432-43.
3235 Oehler C, et al.&#x0D; The microtubule stabilizer patupilone (epothilone B) is a potent radiosensitizer in medulloblastoma cells.&#x0D; Neuro Oncol. 2011 Sep;13(9):1000-10.
3236 Han H, et al. Small-Molecule MYC Inhibitors Suppress Tumor Growth and Enhance Immunotherapy. Cancer Cell. 2019 Nov 11;36(5):483-497.e15.
3237 Akbulut O, et al. A Highly Potent TACC3 Inhibitor as a Novel Anti-cancer Drug Candidate. Mol Cancer Ther. 2020 Mar 26. pii: molcanther.0957.2019.
3238 Röhm S, et al. Fast Iterative Synthetic Approach toward Identification of Novel Highly Selective p38 MAP Kinase Inhibitors. J Med Chem. 2019 Dec 12;62(23):10757-10782.
3239 Farmaco Ed Prat 30:252 (1974); Antimicrob Agents Chemother 7:441 (1975)
3240 Sakamoto K, et al. Effect of ASP6432, a Novel Type 1 Lysophosphatidic Acid Receptor Antagonist, on Urethral Function and Prostate Cell Proliferation. J Pharmacol Exp Ther. 2018 Aug;366(2):390-396.
3241 Okamoto M, et al. Identification of death-associated protein kinases inhibitors using structure-based virtual screening. J Med Chem. 2009 Nov 26;52(22):7323-7.
3242 Ayyagari VN, et al. Bithionol inhibits ovarian cancer cell growth in vitro - studies on mechanism(s) of action. BMC Cancer. 2014 Feb 4;14:61.
3243 Florent RL, et al. In vitro toxicity of bithionol and bithionol sulphoxide to Neoparamoeba spp., the causative agent of amoebic gill disease (AGD). Dis Aquat Organ. 2010 Sep 17;91(3):257-62.
3244 J Chem Soc 1953: 571
3245 J Steroid Biochem 30:391 (1988)|
3246 Di Salle, E., et al., Novel aromatase and 5 alpha-reductase inhibitors. J Steroid Biochem Mol Biol, 1994. 49(4-6): p. 289-94.
3247 Miki, Y, et al. Effects of aromatase inhibitors on human osteoblast and osteoblast-like cells: a possible androgenic bone protective effects induced by exemestane. Bone. 2004 Sep 1;10(17):5717-23.
3248 Goss, P.E., et al., Effects of the steroidal aromatase inhibitor exemestane and the nonsteroidal aromatase inhibitor letrozole on bone and lipid metabolism in ovariectomized rats. Clin Cancer Res, 2004. 10(17): p. 5717-23.
3249 Zaccheo, T., D. Giudici, and E. Di Salle, Inhibitory effect of combined treatment with the aromatase inhibitor exemestane and tamoxifen on DMBA-induced mammary tumors in rats. J Steroid Biochem Mol Biol, 1993. 44(4-6): p. 677-80.
3250 Lu D, et al. Salinomycin inhibits Wnt signaling and selectively induces apoptosis in chronic lymphocytic leukemia cells. Proc Natl Acad Sci U S A. 2011 Aug 9;108(32):13253-7.
3251 Zhou J, et al. Salinomycin induces apoptosis in cisplatin-resistant colorectal cancer cells by accumulation of reactiveoxygen species. Toxicol Lett. 2013 Oct 24;222(2):139-45.
3252 Klose J, et al. Salinomycin: Anti-tumor activity in a pre-clinical colorectal cancer model. PLoS One. 2019 Feb 14;14(2):e0211916.
3253 Wang F, et al. Salinomycin Inhibits Proliferation and Induces Apoptosis of Human Hepatocellular Carcinoma Cells In Vitro and In Vivo. PLoS One. 2012; 7(12): e50638.
3254 Qu H, et al. Effect of salinomycin on metastasis and invasion of bladder cancer cell line T24. Asian Pac J Trop Med. 2015 Jul;8(7):578-82.
3255 https://clinicaltrials.gov/ct2/show/NCT04578236?term=Retinoic+acid&cond=covid&draw=2&rank=2
3256 Lu ML, et al. Potential Signaling Pathways Involved in the Clinical Application of Oxymatrine. Phytother Res. 2016 Jul;30(7):1104-12.
3257 Wu C, et al. Oxymatrine inhibits the proliferation of prostate cancer cells in vitro and in vivo. Mol Med Rep. 2015 Jun;11(6):4129-34.
3258 Wu XL, et al. Effect of Oxymatrine on the TGFbeta-Smad signaling pathway in rats with CCl4-induced hepatic fibrosis. World J Gastroenterol. 2008 Apr 7;14(13):2100-5.
3259 Ding Y, et al. Oxymatrine Inhibits Bocavirus MVC Replication, Reduces Viral Gene Expression and Decreases Apoptosis Induced by Viral Infection. Virol Sin. 2019 Feb;34(1):78-87. |Forestry Res 17:323 (2006); Brain Res 1268:174 (2009); Basic Clin Pharmacol Toxicol 107:906 (2010)
3260 JACS 91:2684 (1969); Science 170:81 (1970)|
3261 Magnuson, B.A., et al., Aspartame: a safety evaluation based on current use levels, regulations, and toxicological and epidemiological studies. Crit Rev Toxicol, 2007. 37(8): p. 629-727.
3262 Humphries, P., E. Pretorius, and H. Naude, Direct and indirect cellular effects of aspartame on the brain. Eur J Clin Nutr, 2008. 62(4): p. 451-62.
3263 Arzneim. Forsch. (1968), 18(7), 791-8; Ther. Ggw. (1911), 51, 348-51
3264 https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=NALTREXONE+&cntry=&state=&city=&dist=&Search=Search
3265 Schaeffer EM, et al.Selective Depletion of Uropathogenic E. coli from the Gut by a FimH Antagonist.SelectivJ Urol. 2018 Apr;199(4):874-875.
3266 Zlitni S, et al. Metabolic suppression identifies new antibacterial inhibitors under nutrient limitation. Nat Chem Biol. 2013 Dec;9(12):796-804.
3267 Shintani Y, et al. ADH-1 suppresses N-cadherin-dependent pancreatic cancer progression. Int J Cancer. 2008 Jan 1;122(1):71-7.
3268 Li H, et al. ADH1, an N-cadherin inhibitor, evaluated in preclinical models of angiogenesis and androgen-independent prostate cancer. Anticancer Drugs. 2007 Jun;18(5):563-8.
3269 Turley RS, et al. Targeting N-cadherin increases vascular permeability and differentially activates AKT in melanoma. Ann Surg. 2015 Feb;261(2):368-77
3270 Curr Ther Res 53:484 (1993); CNS Drugs 2:313 (1994)
3271 Tao H, et al. Small molecule antagonists in distinct binding modes inhibit drug-resistant mutant of smoothened. Chem Biol. 2011 Apr 22;18(4):432-7.
3272 Verena V. Metz, et al. Induction of RAGE Shedding by Activation of G Protein-Coupled Receptors. PLoS One. 2012.
3273 M J M Gooden, et al. Elevated serum CXCL16 is an independent predictor of poor survival in ovarian cancer and may reflect pro-metastatic ADAM protease activity. British Journal of Cancer (2014) 110, 1535–1544.
3274 N Milosch, et al. Holo-APP and G-protein-mediated signaling are required for sAPPa-induced activation of the Akt. Cell Death Dis. 2014 Aug 28;5:e1391.
3275 Rofecoxib, et al. Rofecoxib [Vioxx, MK-0966; 4-(4'-methylsulfonylphenyl)-3-phenyl-2-(5H)-furanone]: a potent and orally active cyclooxygenase-2 inhibitor. Pharmacological and biochemical profiles. J Pharmacol Exp Ther. 1999 Aug;290(2):551-60.
3276 Liu NN, et al. Rofecoxib inhibits retinal neovascularization via down regulation of cyclooxygenase-2 and vascular endothelial growth factor expression. Clin Exp Ophthalmol. 2015 Jul;43(5):458-65.
3277 Stoppoloni D, et al. Synergistic effect of gefitinib and rofecoxib in mesothelioma cells. Mol Cancer. 2010 Feb 2;9:27.
3278 Julie Kim,et al.The Novel Small-Molecule SR18662 Efficiently Inhibits the Growth of Colorectal Cancer In Vitroand In Vivo.Mol Cancer Ther.2019 Nov;18(11):1973-1984.
3279 Drugs (2001), 61(3), 353-364; J. Med. Chem. (1970), 13(6), 1102-5; J. Med. Chem. (1967), 10(4), 530-3|
3280 Ryan A, et al. Activation of nitrofurazone by azoreductases: multiple activities in one enzyme. Sci Rep. 2011;1:63.
3281 CA 72:77299y (1970); Anla Profiles Drug Subs 12:683 (1983)
3282 Meng F, et al. Enhancement of hypoxia-activated prodrug TH-302 anti-tumor activity by Chk1 inhibition. BMC Cancer. 2015 May 21;15:422.
3283 Zhang X, et al. MR Imaging Biomarkers to Monitor Early Response to Hypoxia-Activated Prodrug TH-302 in Pancreatic Cancer Xenografts. PLoS One. 2016 May 26;11(5):e0155289.
3284 Peeters SG, et al. TH-302 in Combination with Radiotherapy Enhances the Therapeutic Outcome and Is Associated with Pretreatment [&lt;sup&gt;18&lt;/sup&gt;F]HX4 Hypoxia PET Imaging. Clin Cancer Res. 2015 Jul 1;21(13):2984-92.
3285 Helv Chim Acta 9:1207 (1951); J Pharmacol Exper Therap 219:540 (1981); Arch Opthalmol 102:1385 (1984)
3286 Roberts AM, et al. Chemoproteomic Screening of Covalent Ligands Reveals UBA5 As a Novel Pancreatic Cancer Target. ACS Chem Biol. 2017 Apr 21;12(4):899-904.
3287 Müller J, et al. Discovery of chromone-based inhibitors of the transcription factor STAT5. Chembiochem. 2008 Mar 25;9(5):723-7.
3288 J Chem Soc 1929:24; Biochem Pharmacol 45:67 (1993); The Antiseptic 99: 81 (2002)
3289 Beard RL, et al. Synthesis and biological activity of retinoic acid receptor-alpha specific amides. Bioorg Med Chem Lett. 2002 Nov 4;12(21):3145-8.
3290 J Am Chem Soc 72:1824 (1950)
3291 David E.Jackson, et al. Aryltetralin lignans from Podophyllum hexandrum and Podophyllum peltatum. Phytochemistry, 1984, 23(5): 1147-1152.
3292 Zilla MK, et al. 4'-Demethyl-deoxypodophyllotoxin glucoside isolated from Podophyllum hexandrum exhibits potential anticancer activities by altering Chk-2 signaling pathway in MCF-7 breast cancer cells. Chem Biol Interact. 2014 Dec 5;224:100-7.
3293 https://clinicaltrials.gov/ct2/show/NCT04900155?term=Ezetimibe&cond=COVID-19&draw=2&rank=1
3294 Zhu Jf, et al. Icaritin shows potent anti-leukemia activity on chronic myeloid leukemia in vitro and in vivo by regulating MAPK/ERK/JNK and JAK2/STAT3 /AKT signalings. PLoS One. 2011;6(8):e23720.
3295 Yao D, et al. Icaritin, an exogenous phytomolecule, enhances osteogenesis but not angiogenesis--an in vitro efficacy study. PLoS One. 2012;7(8):e41264.
3296 Guo Y, et al. An anticancer agent icaritin induces sustained activation of the extracellular signal-regulated kinase (ERK) pathway and inhibits growth of breast cancer cells. Eur J Pharmacol. 2011 May 11;658(2-3):114-22.
3297 Chua GNL, et al. Cytosine-Based TET Enzyme Inhibitors. ACS Med Chem Lett. 2019 Jan 31;10(2):180-185.
3298 Gao Y, et al. Effects of D-Pinitol on Insulin Resistance through the PI3K/Akt Signaling Pathway in Type 2Diabetes Mellitus Rats. J Agric Food Chem. 2015 Jul 8;63(26):6019-26.
3299 Moreira LN, et al. Activation of eNOS by D-pinitol Induces an Endothelium-Dependent Vasodilatation in MouseMesenteric Artery. Front Pharmacol. 2018 May 22;9:528.
3300 Rengarajan T, et al. D-pinitol promotes apoptosis in MCF-7 cells via induction of p53 and Bax and inhibition of Bcl-2 and NF-κB. Asian Pac J Cancer Prev. 2014;15(4):1757-62.
3301 Sethi G, et al. Pinitol targets nuclear factor-kappaB activation pathway leading to inhibition of gene products associated with proliferation, apoptosis, invasion, and angiogenesis. Mol Cancer Ther. 2008 Jun;7(6):1604-14.
3302 Shen J, et al. Protodioscin ameliorates fructose-induced renal injury via inhibition of the mitogen activated protein kinase pathway. Phytomedicine. 2016 Nov 15;23(12):1504-1510.
3303 Zhang X, et al. Potential neuroprotection of protodioscin against cerebral ischemia-reperfusion injury in rats through intervening inflammation and apoptosis. Steroids. 2016 Sep;113:52-63
3304 Wang T, et al. Antihyperlipidemic effect of protodioscin, an active ingredient isolated from the rhizomes of Dioscorea nipponica. Planta Med. 2010 Oct;76(15):1642-6
3305 Siebeneicher H et al. Identification and Optimization of the First Highly Selective GLUT1 Inhibitor BAY-876. ChemMedChem. 2016 Aug 23.
3306 Ma Y, et al. Ovarian Cancer Relies on Glucose Transporter 1 to Fuel Glycolysis and Growth: Anti-Tumor Activity of BAY-876. Cancers (Basel). 2018 Dec 31;11(1).
3307 Christensen JG, et al. The KRASG12C Inhibitor, MRTX849, Provides Insight Toward Therapeutic Susceptibility of KRAS Mutant Cancers in Mouse Models and Patients. Cancer Discov. 2019 Oct 28. pii: CD-19-1167.
3308 Kyriakos P. Papadopoulos, et al. A phase I/II multiple expansion cohort trial of MRTX849 in patients with advanced solid tumors with KRAS G12C mutation. Journal of Clinical Oncology 2019 37:15_suppl, TPS3161-TPS3161.
3309 Osaki S, et al. L-arabinose feeding prevents increases due to dietary sucrose in lipogenic enzymes and triacylglycerol levels in rats. J Nutr. 2001 Mar;131(3):796-9.
3310 Huck JH, et al. Ribose-5-phosphate isomerase deficiency: new inborn error in the pentose phosphate pathway associated with a slowly progressive leukoencephalopathy. Am J Hum Genet. 2004 Apr;74(4):745-51.
3311 Nakamura T, et al. Synthesis and evaluation of 8-oxoadenine derivatives as potent Toll-like receptor 7 agonists with high water solubility. Bioorg Med Chem Lett. 2013 Feb 1;23(3):669-72.
3312 Adlard AL, et al. A novel systemically administered Toll-like receptor 7 agonist potentiates the effect of ionizing radiation in murine solid tumor models. Int J Cancer. 2014 Aug 15;135(4):820-9.
3313 Expert Opin. Pharmacother. (2010), 11(18), 3085-3093; Res. Clin. Stud. Headache (1978), 6, 6-12; J. Pharmacol. (1947), 90, 166-73|
3314 Colman, I., et al., Parenteral dihydroergotamine for acute migraine headache: a systematic review of the literature. Ann Emerg Med, 2005. 45(4): p. 393-401.
3315 Saper, J.R., et al., DHE in the pharmacotherapy of migraine: potential for a larger role. Headache, 2006. 46 Suppl 4: p. S212-20.
3316 Schaerlinger, B., et al., Agonist actions of dihydroergotamine at 5-HT2B and 5-HT2C receptors and their possible relevance to antimigraine efficacy. Br J Pharmacol, 2003. 140(2): p. 277-84.
3317 Forster M, et al. Selective JAK3 Inhibitors with a Covalent Reversible Binding Mode Targeting a New Induced Fit Binding Pocket. Cell Chem Biol. 2016 Nov 17;23(11):1335-1340.
3318 Bartholomeusz GA, et al. Activation of a novel Bcr/Abl destruction pathway by WP1130 induces apoptosis of chronic myelogenous leukemia cells. Blood. 2007 Apr 15;109(8):3470-8.
3319 Adv Carbohydr Chem 3:337 (1948); Anal Profiles Drug Subs 16:507 (1986)
3320 Drugs Aging (2005), 22(11), 967-977; Drugs Aging (1996), 8(4), 299-322; Bull. Soc. Chim. Fr. (1966), (6), 1838-46
3321 https://clinicaltrials.gov/ct2/show/NCT04884490?term=TRIMETHOPRIM&cond=Covid19&draw=2&rank=1 https://clinicaltrials.gov/ct2/show/NCT04470531?term=TRIMETHOPRIM&cond=Covid19&draw=2&rank=2 https://trialsearch.who.int/Trial2.aspx?TrialID=EUCTR2020-001466-11-GR
3322 Islam I, et al. Discovery of selective urokinase plasminogen activator (uPA) inhibitors as a potential treatment for multiple sclerosis. Bioorg Med Chem Lett. 2018 Nov 1;28(20):3372-3375.
3323 Takemura T, et al. 3,4-Dicaffeoylquinic Acid, a Major Constituent of Brazilian Propolis, Increases TRAIL Expression and Extends the Lifetimes of Mice Infected with the Influenza A Virus. Evid Based Complement Alternat Med. 2012;2012:946867.
3324 Liu X, et al. Protective effect of isochlorogenic acid B on liver fibrosis in non-alcoholic steatohepatitis of mice. Basic Clin Pharmacol Toxicol. 2019;124(2):144-153.
3325 Ooi KL, et al. Cytotoxic, apoptotic and anti-α-glucosidase activities of 3,4-di-O-caffeoyl quinic acid, an antioxidant isolated from the polyphenolic-rich extract of Elephantopus mollis Kunth. J Ethnopharmacol. 2011;135(3):685-695.
3326 https://clinicaltrials.gov/ct2/show/NCT04467931?term=METHYLDOPA&cond=covid&draw=2&rank=1
3327 Zhou HJ, et al. Design and synthesis of an orally bioavailable and selective peptide epoxyketone proteasome inhibitor (PR-047). J Med Chem. 2009 May 14;52(9):3028-38.
3328 Chauhan D, et al. A novel orally active proteasome inhibitor ONX 0912 triggers in vitro and in vivo cytotoxicity in multiple myeloma. Blood, 2010, 116(23), 4906-4915.
3329 Muchamuel T, et al. A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis. Nat Med, 2009, 15(7), 781-787.
3330 Hagen Thieme, et al. Endothelin antagonism: effects of FP receptor agonists prostaglandin F2alpha and fluprostenol on trabecular meshwork contractility. Invest Ophthalmol Vis Sci. 2006 Mar;47(3):938-45.
3331 Xin Wen, et al. Prostaglandin F2α Induces Goat Corpus Luteum Regression via Endoplasmic Reticulum Stress and Autophagy. Front Physiol. 2020 Sep 11;11:868.
3332 Yurtsever Z, et al. First comprehensive structural and biophysical analysis of MAPK13 inhibitors targeting DFG-in and DFG-out binding modes. Biochim Biophys Acta. 2016 Nov;1860(11 Pt A):2335-2344.
3333 Mehdi Bouhaddou, et al. The Global Phosphorylation Landscape of SARS-CoV-2 Infection. Cell. 2020 Aug 6;182(3):685-712.e19.
3334 Tijsma A, et al. The capsid binder Vapendavir and the novel protease inhibitor SG85 inhibit enterovirus 71 replication. Antimicrob Agents Chemother. 2014 Nov;58(11):6990-2.
3335 Sun L, et al. Antiviral Activity of Broad-Spectrum and Enterovirus-Specific Inhibitors against Clinical Isolates of Enterovirus D68. Antimicrob Agents Chemother. 2015 Dec;59(12):7782-5.
3336 Martin MW, et al. Discovery of novel N-hydroxy-2-arylisoindoline-4-carboxamides as potent and selective inhibitors of HDAC11. Bioorg Med Chem Lett. 2018 Jul 1;28(12):2143-2147.
3337 Gynecol Prat 15:247 (1964); Genitourin Med 73:397 (1997); Clin Infect Dis 49:914 (2009)
3338 O'Neill BT, et al. Design and Synthesis of Clinical Candidate PF-06751979: A Potent, Brain Penetrant, β-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) Inhibitor Lacking Hypopigmentation. J Med Chem. 2018 May 24;61(10):4476-4504.
3339 M Titford. The long history of hematoxylin. Biotech Histochem. Mar-Apr 2005;80(2):73-8.
3340 Yilong Tu, et al. Hematoxylin Inhibits Amyloid β-Protein Fibrillation and Alleviates Amyloid-Induced Cytotoxicity. J Phys Chem B. 2016 Nov 10;120(44):11360-11368.
3341 Ada T Feldman, et al. Tissue processing and hematoxylin and eosin staining. Methods Mol Biol. 2014;1180:31-43.
3342 Robert D Cardiff, et al. Manual hematoxylin and eosin staining of mouse tissue sections. Cold Spring Harb Protoc. 2014 Jun 2;2014(6):655-8.
3343 Mitsui I, et al. A new water-soluble camptothecin derivative, DX-8951f, exhibits potent antitumor activity against human tumors in vitro and in vivo. Jpn J Cancer Res. 1995 Aug;86(8):776-82.
3344 Sun FX, et al. Efficacy of camptothecin analog DX-8951f (Exatecan Mesylate) on human pancreatic cancer in an orthotopic metastatic model. Cancer Res. 2003 Jan 1;63(1):80-5.
3345 Joto N, et al. DX-8951f, a water-soluble camptothecin analog, exhibits potent antitumor activity against a human lung cancer cell line and its SN-38-resistant variant. Int J Cancer. 1997 Aug 7;72(4):680-6.
3346 Bola BM, et al. Inhibition of monocarboxylate transporter-1 (MCT1) by AZD3965 enhances radiosensitivity by reducing lactate transport. Mol Cancer Ther. 2014 Dec;13(12):2805-16.
3347 Polanski R, et al. Activity of the monocarboxylate transporter 1 inhibitor AZD3965 in small cell lung cancer. Clin Cancer Res. 2014 Feb 15;20(4):926-37.
3348 Bold G, et al. A Novel Potent Oral Series of VEGFR2 Inhibitors Abrogate Tumor Growth by Inhibiting Angiogenesis. J Med Chem. 2016 Jan 14;59(1):132-46.
3349 Galyean ML, et al. Effects of arrival medication with tilmicosin phosphate on health and performance of newly received beef cattle. J Anim Sci. 1995 May;73(5):1219-26.
3350 Fittipaldi N, et al. Assessment of the efficacy of tilmicosin phosphate to eliminate Actinobacillus pleuropneumoniae from carrier pigs. Can J Vet Res. 2005 Apr;69(2):146-50.
3351 Chem Pharm Bull 33:3982 (1985): Phytochemistry 28:1778 (1989)
3352 Christodoulou MS, et al. Synthesis and biological evaluation of imidazolo[2,1-b]benzothiazole derivatives, as potential p53 inhibitors. Bioorg Med Chem. 2011 Mar 1;19(5):1649-57.
3353 Fernández-Cruz ML, et al. Biological and chemical studies on aryl hydrocarbon receptor induction by the p53 inhibitor pifithrin-α and its condensation productpifithrin-β. Life Sci. 2011 Apr 25;88(17-18):774-83.
3354 Da Pozzo E, et al. p53 functional inhibitors behaving like pifithrin-β counteract the Alzheimer peptide non-β-amyloid component effects in human SH-SY5Y cells. ACS Chem Neurosci. 2014 May 21;5(5):390-9.
3355 Jeffrey R. Jackson, et al. A second generation KSP inhibitor, SB-743921, is a highly potent and active therapeutic in preclinical models of cancer. First AACR International Conference on Molecular Diagnostics in Cancer Therapeutic Development, Sep 12-15, 2006.
3356 Yin Y, et al. Kinesin spindle protein inhibitor SB743921 induces mitotic arrest and apoptosis and overcomes imatinib resistance of chronic myeloid leukemia cells. Leuk Lymphoma. 2015 Jun;56(6):1813-20.
3357 Good JA, et al. Optimized S-trityl-L-cysteine-based inhibitors of kinesin spindle protein with potent in vivo antitumor activity in lung cancer xenograft models. J Med Chem. 2013 Mar 14;56(5):1878-93.
3358 Akamatsu M, et al. Conversion of antigen-specific effector/memory T cells into Foxp3-expressing Treg cells by inhibition of CDK8/19. Sci Immunol. 2019 Oct 25;4(40). pii: eaaw2707.
3359 J Cell Biol 115:461 (1991);122:523 (1993); Eur J Biochem 248:30 (1997)|
3360 Obrecht AS, et al. Identification of aurintricarboxylic acid as a potent allosteric antagonist of P2X1 and P2X3 receptors. Neuropharmacology. 2019 Nov 1;158:107749.
3361 Hashem AM, et al. Aurintricarboxylic acid is a potent inhibitor of influenza A and B virus neuraminidases. PLoS One. 2009 Dec 17;4(12):e8350.
3362 Benchokroun Y, et al. Aurintricarboxylic acid, a putative inhibitor of apoptosis, is a potent inhibitor of DNA topoisomerase II in vitro and in Chinese hamster fibrosarcoma cells. Biochem Pharmacol. 1995 Jan 31;49(3):305-13.
3363 Alison Roos, et al. Identification of aurintricarboxylic acid as a selective inhibitor of the TWEAK-Fn14 signaling pathway in glioblastoma cells. Oncotarget. 2017 Feb 14; 8(7): 12234–12246.
3364 Youtian Hu, et al. Discovery of a Bioactive Inhibitor with a New Scaffold for Cystathionine γ-Lyase. J Med Chem. 2019 Feb 14;62(3):1677-1683.
3365 Rengen Fan, et al. Small molecules with big roles in microRNA chemical biology and microRNA-targeted therapeutics. RNA Biol. 2019 Jun; 16(6): 707–718.
3366 Kobori M, et al. Wedelolactone suppresses LPS-induced caspase-11 expression by directly inhibiting the IKK complex. Cell Death Differ. 2004 Jan;11(1):123-30.
3367 Sarveswaran S, et al. Wedelolactone, a medicinal plant-derived coumestan, induces caspase-dependent apoptosis in prostate cancer cells via downregulation of PKCε without inhibiting Akt. Int J Oncol. 2012 Dec;41(6):2191-9.
3368 Liu YQ, et al. Wedelolactone enhances osteoblastogenesis by regulating Wnt/β-catenin signaling pathway but suppresses osteoclastogenesis by NF-κB/c-fos/NFATc1 pathway. Sci Rep. 2016 Aug 25;6:32260.
3369 Wang S, et al. N-Oleoyl glycine, a lipoamino acid, stimulates adipogenesis associated with activation of CB1 receptor and Akt signaling pathway in 3T3-L1 adipocyte. Biochem Biophys Res Commun. 2015 Oct 23;466(3):438-43.
3370 Japan J Pharmacol 50:47 (1989); Arzneim Forsch 44:193 (1994)
3371 Kazi A, et al. Dual farnesyl and geranylgeranyl transferase inhibitor thwarts mutant KRAS-driven patient-derived pancreatic tumors. Clin Cancer Res. 2019 Jun 21.
3372 Smith JA, et al. Identification of the first specific inhibitor of p90 ribosomal S6 kinase (RSK) reveals an unexpected role for RSK in cancer cell proliferation. Cancer Res. 2005 Feb 1;65(3):1027-34.
3373 Yu Li, et al. The Affinity of RSK for Cylitol Analogues of SL0101 Is Critically Dependent on the B-ring C-4'-hydroxy. Chem Commun (Camb). 2020 Mar 10;56(20):3058-3060.
3374 Mender I, et al. Induction of telomere dysfunction mediated by the telomerase substrate precursor 6-thio-2'-deoxyguanosine. Cancer Discov. 2015 Jan;5(1):82-95.
3375 Hegde SS, et al. Pharmacologic characterization of GSK-961081 (TD-5959), a first-in-class inhaled bifunctional bronchodilator possessing muscarinic receptor antagonist and β2-adrenoceptor agonist properties. J Pharmacol Exp Ther. 2014 Oct;351(1):190-9.
3376 Hughes AD, et al. Discovery of (R)-1-(3-((2-chloro-4-(((2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl)amino)methyl)-5-methoxyphenyl)amino)-3-oxopropyl)piperidin-4-yl [1,1'-biphenyl]-2-ylcarbamate (TD-5959, GSK961081, batefenterol): first-in-class dual pharmacology multivalent muscarinic antagonist and β? agonist (MABA) for the treatment of chronic obstructive pulmonary disease (COPD). J Med Chem. 2015 Mar 26;58(6):2609-22.
3377 Russo R, et al. Effects of 6-aminochrysene on liver microsomal enzyme activity. Xenobiotica. 1976 Apr;6(4):201-5.
3378 Lambelin G, et al. Carcinogenicity of 6-aminochrysene in mice. Eur J Cancer. 1975 May;11(5):327-34.
3379 Yamazaki R, et al. Novel acrylonitrile derivatives, YHO-13177 and YHO-13351, reverse BCRP/ABCG2-mediated drug resistance in vitro and in vivo. Mol Cancer Ther. 2011 Jul;10(7):1252-63.
3380 Shishido Y, et al. ABCG2 inhibitor YHO-13351 sensitizes cancer stem/initiating-like side population cells to irinotecan. Anticancer Res. 2013 Apr;33(4):1379-86.
3381 Maderna A, et al. Discovery of cytotoxic dolastatin 10 analogues with N-terminal modifications. J Med Chem. 2014 Dec 26;57(24):10527-43.
3382 Bao R, et al. CUDC-305, a novel synthetic HSP90 inhibitor with unique pharmacologic properties for cancer therapy. Clin Cancer Res. 2009 Jun 15;15(12):4046-57.
3383 Stenderup K, et al. Debio 0932, a new oral Hsp90 inhibitor, alleviates psoriasis in a xenograft transplantation model. Acta Derm Venereol. 2014 Nov;94(6):672-6.
3384 Bao R, et al. Targeting heat shock protein 90 with CUDC-305 overcomes erlotinib resistance in non-small cell lung cancer. Mol Cancer Ther. 2009 Dec;8(12):3296-306.
3385 Jin ZL, et al. Cinchonine activates endoplasmic reticulum stress-induced apoptosis in human liver cancer cells. Exp Ther Med. 2018 Jun;15(6):5046-5050. |Acta Pharmacol Toxicol 4:265 (1949)
3386 Clin Toxicol 16:17 (1980); Anal Profiles Drug Subs 14:108 (1985)
3387 Naik R, et al. Synthesis and structure-activity relationship study of chemical probes as hypoxia induced factor-1α/malate dehydrogenase 2 inhibitors. J Med Chem. 2014 Nov 26;57(22):9522-38.
3388 Lee K, et al. LW6, a novel HIF-1 inhibitor, promotes proteasomal degradation of HIF-1alpha via upregulation of VHL in a colon cancer cell line. Biochem Pharmacol. 2010 Oct 1;80(7):982-9.
3389 Song JG, et al. Discovery of LW6 as a new potent inhibitor of breast cancer resistance protein.
3390 Sato M, et al. LW6, a hypoxia-inducible factor 1 inhibitor, selectively induces apoptosis in hypoxic cells through depolarization of mitochondria in A549 human lung cancer cells. Mol Med Rep. 2015 Sep;12(3):3462-8.
3391 Nakano-Ito K, et al. E2012-induced cataract and its predictive biomarkers. Toxicol Sci. 2014 Jan;137(1):249-58.
3392 Portelius E, Van Broeck B, Andreasson U, Gustavsson MK, Mercken M, Zetterberg H, Borghys H, Blennow K.Acute effect on the Aβ isoform pattern in CSF in response to γ-secretase modulator and inhibitor treatment in dogs.J Alzheimers Dis. 2010;21(3):1005-12.
3393 Laco F, et al. Cardiomyocyte differentiation of pluripotent stem cells with SB203580 analogues correlates with Wnt pathway CK1 inhibition independent of p38 MAPK signaling. J Mol Cell Cardiol. 2015 Mar;80:56-70.
3394 Virtanen R, et al. Pharmacological evidence for the involvement of alpha-2 adrenoceptors in the sedative effect of detomidine, a novel sedative-analgesic. J Vet Pharmacol Ther. 1985 Mar;8(1):30-7.
3395 J Still, et al. Cardiovascular and respiratory effects of detomidine in isoflurane-anaesthetised horses. J S Afr Vet Assoc. 1996 Dec;67(4):199-203.
3396 Graub R, et al. Cell cycle-dependent phosphorylation of human CDC5 regulates RNA processing. Cell Cycle. 2008 Jun 15;7(12):1795-803.
3397 Brooks EE, et al. CVT-313, a specific and potent inhibitor of CDK2 that prevents neointimal proliferation. J Biol Chem. 1997 Nov 14;272(46):29207-11.
3398 Chen P, et al. Discovery and Characterization of GSK2801, a Selective Chemical Probe for the Bromodomains BAZ2A and BAZ2B. J Med Chem. 2016 Feb 25;59(4):1410-24.
3399 Ai J, et al. Preclinical Evaluation of SCC244 (Glumetinib), a Novel, Potent, and Highly Selective Inhibitor of c-Met in MET-dependent Cancer Models. Mol Cancer Ther. 2018 Apr;17(4):751-762.
3400 Li J, et al. t-AUCB, an improved sEH inhibitor, suppresses human glioblastoma cell growth by activatingNF-κB-p65. J Neurooncol. 2012 Jul;108(3):385-93.
3401 Liu JY, et al. Pharmacokinetic optimization of four soluble epoxide hydrolase inhibitors for use in a murinemodel of inflammation. Br J Pharmacol. 2009 Jan;156(2):284-96.
3402 Stephen Willingham, et al. Abstract PR04: CPI-444: A potent and selective inhibitor of A2AR induces antitumor responses alone and in combination with anti-PD-L1 in preclinical and clinical studies.Cancer Immunoly Research. September 25-28, 2016.
3403 Indarte M, et al. An Inhibitor of the Pleckstrin Homology Domain of CNK1 Selectively Blocks the Growth of Mutant KRAS Cells and Tumors. Cancer Res. 2019 Jun 15;79(12):3100-3111.
3404 Apraiz, Aintzane., et al. Dihydroceramide accumulation and reactive oxygen species are distinct and nonessential events in 4-HPR-mediated leukemia cell death. Biochemistry and Cell Biology (2012), 90(2), 209-223.
3405 Bikman, Benjamin T., et al. Fenretinide Prevents Lipid-induced Insulin Resistance by Blocking Ceramide Biosynthesis. Journal of Biological Chemistry (2012), 287(21), 17426-17437.
3406 Cooper JP, et al. Fenretinide metabolism in humans and mice: utilizing pharmacological modulation of its metabolic pathway to increase systemic exposure. Br J Pharmacol. 2011 Jul;163(6):1263-75.
3407 Golubkov V, et al. Action of fenretinide (4-HPR) on ovarian cancer and endothelial cells. Anticancer Res. 2005 Jan-Feb;25(1A):249-53.
3408 Prinz H, et al. N-benzoylated phenoxazines and phenothiazines: synthesis, antiproliferative activity, and inhibition of tubulin polymerization. J Med Chem. 2011 Jun 23;54(12):4247-63.
3409 Overstreet DH, et al. Saredutant, an NK2 receptor antagonist, has both antidepressant-like effects and synergizes with Desipramine in an animal model of depression. Pharmacol Biochem Behav. 2010 Aug;96(2):206-10.
3410 Mock ED, et al. Discovery of a NAPE-PLD inhibitor that modulates emotional behavior in mice. Nat Chem Biol. 2020;16(6):667-675.
3411 Wei X, et al. Kojic acid inhibits senescence of human corneal endothelial cells via NF-κB and p21 signaling pathways. Exp Eye Res. 2018 Dec 28;180:174-183.
3412 J Am Chem Soc 61: 2832 (1939)
3413 Zocchi C, et al. Binding of the radioligand [3H]-SCH 58261, a new non-xanthine A2A adenosine receptor antagonist, to rat striatal membranes. Br J Pharmacol. 1996 Apr;117(7):1381-6.
3414 Varani K, et al. Pharmacological and biochemical characterization of purified A2a adenosine receptors in human platelet membranes by [3H]-CGS 21680 binding. Br J Pharmacol. 1996 Apr;117(8):1693-701.
3415 Xi J, et al. Adenosine A2A and A2B receptors work in concert to induce a strong protection against reperfusion injury in rat hearts. J Mol Cell Cardiol. 2009 Nov;47(5):684-90.
3416 Kuzumaki N, et al. Multiple analyses of G-protein coupled receptor (GPCR) expression in the development of gefitinib-resistance in transforming non-small-cell lung cancer. PLoS One. 2012;7(10):e44368.
3417 Mediavilla-Varela M, et al. Antagonism of adenosine A2A receptor expressed by lung adenocarcinoma tumor cells and cancer associated fibroblasts inhibits their growth. Cancer Biol Ther. 2013 Sep;14(9):860-8.
3418 Wardas J, et al. SCH 58261, a selective adenosine A2A receptor antagonist, decreases the haloperidol-enhanced proenkephalin mRNA expression in the rat striatum. Brain Res. 2003 Jul 11;977(2):270-7.
3419 Wardas J, et al. SCH 58261, an A(2A) adenosine receptor antagonist, counteracts parkinsonian-like muscle rigidity in rats. Synapse. 2001 Aug;41(2):160-71.
3420 Anal Biochem 77: 106 (1977); Biochem J 260: 19 (1989); 324: 497 (1997)
3421 Salphati L, et al. Distribution of the phosphatidylinositol 3-kinase inhibitors Pictilisib (GDC-0941) and GNE-317 in U87 and GS2 intracranial glioblastoma models-assessment by matrix-assisted laser desorption ionization imaging. Drug Metab Dispos. 2014 Jul;42(7):1110-6.
3422 Becker CM, et al. Decreased affinity for efflux transporters increases brain penetrance and molecular targeting of a PI3K/mTOR inhibitor in a mouse model of glioblastoma. Neuro Oncol. 2015 Sep;17(9):1210-9.
3423 Arch Ophthalmol 51:663 (1954); Optomitry Vision Sci 74:1025 (1997)
3424 Nature 223:211 (1969); Cancer Res 62:2708 (2002); Mol Pharmacol 62:1255 (2002)
3425 Harriman G, et al. Acetyl-CoA carboxylase inhibition by ND-630 reduces hepatic steatosis, improves insulin sensitivity, and modulates dyslipidemia in rats. Proc Natl Acad Sci U S A. 2016 Mar 29;113(13):E1796-805.
3426 Beghyn, et al. PDE5 inhibitors: An original access to novel potent arylated analogues of tadalafil. Bioorganic &amp; Medicinal Chemistry Letters (2007), 17(3), 789-792.
3427 Daugan, et al. The discovery of tadalafil: a novel and highly selective PDE5 inhibitor. 2: 2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione analogue. Journal of Medicinal Chemistry (2003), 46(21), 4533-4542.
3428 Porst H, et al. Chronic PDE-5 inhibition in patients with erectile dysfunction - a treatment approach using tadalafil once-daily. Expert Opin Pharmacother. 2012 Jul;13(10):1481-94.
3429 Frey MK, Lang I. Tadalafil for the treatment of pulmonary arterial hypertension. Expert Opin Pharmacother. 2012 Apr;13(5):747-55.
3430 Božović M, et al. &lt;i&gt;Calamintha nepeta&lt;/i&gt; (L.) Savi and its Main Essential Oil Constituent Pulegone: Biological Activities and Chemistry. Molecules. 2017 Feb 14;22(2).
3431 Majikina A, et al. Involvement of nociceptive transient receptor potential channels in repellent action of pulegone. Biochem Pharmacol. 2018 May;151:89-95.
3432 Juruena, M.F., E.P. de Sena, and I.R. de Oliveira, Sertindole in the management of schizophrenia. J Cent Nerv Syst Dis, 2011. 3: p. 75-85.
3433 Kane, J.M. and C.A. Tamminga, Sertindole (Serdolect): preclinical and clinical findings of a new atypical antipsychotic. Expert Opin Investig Drugs, 1997. 6(11): p. 1729-41.
3434 Murdoch, D. and G.M. Keating, Sertindole : a review of its use in schizophrenia. CNS Drugs, 2006. 20(3): p. 233-55.
3435 Arch. Dermatol. (1969), 99(6), 753-6; Endocrinology (1965), 76(5), 916-27; Steroids (1964), 4(1), 1-30
3436 David K Edwards V, et al. Targeting of colony-stimulating factor 1 receptor (CSF1R) in the CLL microenvironment yields antineoplastic activity in primary patient samples. Oncotarget. 2018 May 15;9(37):24576-24589.
3437 Dembele L, et al. The Plasmodium PI(4)K inhibitor KDU691 selectively inhibits dihydroartemisinin-pretreated Plasmodium falciparum ring-stage parasites. Sci Rep. 2017;7(1):2325. Published 2017 May 24.
3438 Zeeman AM, et al. PI4 Kinase Is a Prophylactic but Not Radical Curative Target in Plasmodium vivax-Type Malaria Parasites. Antimicrob Agents Chemother. 2016;60(5):2858-2863. Published 2016 Apr 22.
3439 Turnbull AP, et al. Molecular basis of USP7 inhibition by selective small-molecule inhibitors. Nature. 2017 Oct 26;550(7677):481-486.
3440 Hasako S, et al. TAS6417, A Novel EGFR Inhibitor Targeting Exon 20 Insertion Mutations. Mol Cancer Ther. 2018 Aug;17(8):1648-1658.
3441 Hibiki Udagawa, et al. TAS6417/CLN-081 Is a Pan-Mutation-Selective EGFR Tyrosine Kinase Inhibitor with a Broad Spectrum of Preclinical Activity against Clinically Relevant EGFR Mutations. Mol Cancer Res. 2019 Nov;17(11):2233-2243.
3442 Int J Dermatol 24:603 (1985); Crit Rev Toxicol 21:105 (1990); Mutag 7:433 (1992); J Pesticide Reform 18:14 (1998)
3443 Brit J Pharmacol 120:813 (1997); Arch Dis Child 84:430 (2001)
3444 Annalen 520:31 (1935); J Biol Chem 126:29 (1938); Indian J Exper Biol 37:415 (1999)
3445 Liu Z, et al. Discovery of 3-(Indol-5-yl)-indazole Derivatives as Novel Myeloid Differentiation Protein 2/Toll-like Receptor 4 Antagonists for Treatment of Acute Lung Injury. J Med Chem. 2019 Jun 13;62(11):5453-5469.
3446 Fortschr Med 97:883 (1979); Arzneim Forsch 33:453 (1983)
3447 Medhurst AD, et al. GSK189254, a novel H3 receptor antagonist that binds to histamine H3 receptors in Alzheimer's disease brain and improves cognitive performance in preclinical models. J Pharmacol Exp Ther. 2007 Jun;321(3):1032-45.
3448 Guo RX, et al. Differential effects of acute and repeat dosing with the H3 antagonist GSK189254 on the sleep-wake cycle and narcoleptic episodes in Ox-/- mice.Br J Pharmacol. 2009 May;157(1):104-17.
3449 Locher CP, et al. A novel inhibitor of gyrase B is a potent drug candidate for treatment of tuberculosis and nontuberculosis mycobacterial infections. Antimicrob Agents Chemother. 2015 Mar;59(3):1455-65.
3450 J Pharmacol Exp Ther 186:173 (1973); J Urol 119:9 (1978); Urology17:320 (1981)
3451 Rheumatology (1999), 38 Suppl 11-3; Inflammation Res. (1998), 47(2), 79-85; Arzneim. Forsch. (1995), 45(10), 1093-5,|
3452 Vago T, et al. Effect of nimesulide action time dependence on selectivity towards prostaglandin G/H synthase/cyclooxygenase activity. Arzneimittelforschung. 1995 Oct;45(10):1096-8.
3453 Werner MF, et al. Nimesulide-induced antipyresis in rats involves both cyclooxygenase-dependent and independent mechanisms. Eur J Pharmacol. 2006 Aug 14;543(1-3):181-9.
3454 Genç S, et al. The effect of COX-2 inhibitor, nimesulide, on angiogenetic factors in primary endometrial carcinoma cell culture. Clin Exp Med. 2007 Mar;7(1):6-10.
3455 https://clinicaltrials.gov/ct2/show/NCT04937543?term=BECLOMETHASONE&cond=COVID-19&draw=2&rank=2
3456 Costell MH, et al. Comparison of soluble guanylate cyclase stimulators and activators in models of cardiovascular disease associated with oxidative stress. Front Pharmacol. 2012 Jul 5;3:128.
3457 Zhao X, et al. Pharmacokinetics of the Soluble Guanylate Cyclase Stimulator Riociguat in Healthy Young Chinese Male Non-Smokers and Smokers: Results of a Randomized, Double-Blind, Placebo-Controlled Study. Clin Pharmacokinet. 2016 May;55(5):615-24.
3458 Oudot A, et al. Combination of BAY 60-4552 and vardenafil exerts proerectile facilitator effects in rats with cavernous nerve injury: a proof of concept study for the treatment of phosphodiesterase type 5 inhibitor failure. Eur Urol. 2011 Nov;60(5):1020-6.
3459 Suzuki H, et al. Bropirimine inhibits osteoclast differentiation through production of interferon-β. Biochem Biophys Res Commun. 2015;467(1):146‐151.
3460 Sarosdy MF, et al. Oral bropirimine immunotherapy of bladder carcinoma in situ after prior intravesical bacille Calmette-Guérin. Urology. 1998;51(2):226‐231.
3461 Arnold LD, et al. Pyrrolo[2,3-d]pyrimidines containing an extended 5-substituent as potent and selective inhibitors of lck I. Bioorg Med Chem Lett. 2000 Oct 2;10(19):2167-70.
3462 Seo HH, et al. 7-cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d] pyrimidin-4-ylamine inhibits the proliferation and migration of vascular smooth muscle cells by suppressing ERK and Akt pathways. Eur J Pharmacol. 2017 Mar 5;798:35-42.
3463 Burchat AF, et al. Pyrrolo[2,3-d]pyrimidines containing an extended 5-substituent as potent and selective inhibitorsof lck II. Bioorg Med Chem Lett. 2000 Oct 2;10(19):2171-4.
3464 Antimicrob Agents Chemother 29:193 (1986); 30:689 (1986
3465 https://clinicaltrials.gov/ct2/show/NCT04278404?term=AMINOCAPROIC+ACID&cond=covid&draw=2&rank=1
3466 Antimicrob. Agents Chemother. (1979), 15(3), 392-5; Antimicrob. Agents Chemother. (1977), 12(3), 353-6; Mol. Pharmacol. (1970), 6(6), 604-16|
3467 Layton HW, et al. Efficacy of nithiamide in preventing and treating swine dysentery in experimentally inoculated pigs. Am J Vet Res. 1977 May;38(5):627-31.
3468 Wen Ma, et al. A Cell Membrane-Targeting Self-Delivery Chimeric Peptide for Enhanced Photodynamic Therapy and In Situ Therapeutic Feedback. Adv Healthc Mater. 2020 Jan;9(1):e1901100.
3469 Maksim V Kvach, et al. 5(6)-carboxyfluorescein revisited: new protecting group, separation of isomers, and their spectral properties on oligonucleotides. Bioconjug Chem. Sep-Oct 2007;18(5):1691-6.
3470 Knox K, et al. The Coumarin Glucoside, Esculin, Reveals Rapid Changes in Phloem-Transport Velocity in Response to Environmental Cues. Plant Physiol. 2018 Oct;178(2):795-807.
3471 Song Y, et al. Esculin ameliorates cognitive impairment in experimental diabetic nephropathy and induces anti-oxidative stress and anti-inflammatory effects via the MAPK pathway. Mol Med Rep. 2018 May;17(5):7395-7402.
3472 So L, et al. Selective inhibition of phosphoinositide 3-kinase p110α preserves lymphocyte function. J Biol Chem. 2013 Feb 22;288(8):5718-31.
3473 Tomoyuki Hasegawa, et al. Process Development of ONO-2506:  A Therapeutic Agent for Stroke and Alzheimer's Disease. Org. Process Res. Dev.200372168-171.
3474 Kato H, et al. Arundic acid, an astrocyte-modulating agent, protects dopaminergic neurons against MPTPneurotoxicity in mice. Brain Res. 2004 Dec 24;1030(1):66-73.
3475 https://clinicaltrials.gov/ct2/show/NCT05004753?term=Artemisinin&cond=covid-19&draw=2&rank=1
3476 J R Schultz, et al. Role of LXRs in Control of Lipogenesis. Genes Dev. 2000 Nov 15;14(22):2831-8.
3477 Rough JJ, et al. Anti-proliferative effect of LXR agonist T0901317 in ovarian carcinoma cells. J Ovarian Res. 2010 May 26;3:13.
3478 Todd G Kirchgessner, et al. Beneficial and Adverse Effects of an LXR Agonist on Human Lipid and Lipoprotein Metabolism and Circulating Neutrophils. Cell Metab. 2016 Aug 9;24(2):223-33.
3479 Keith A Houck, et al. T0901317 Is a Dual LXR/FXR Agonist. Mol Genet Metab. Sep-Oct 2004;83(1-2):184-7.
3480 Naresh Kumar, et al. The Benzenesulfoamide T0901317 [N-(2,2,2-trifluoroethyl)-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]-benzenesulfonamide] Is a Novel Retinoic Acid Receptor-Related Orphan Receptor-Alpha/Gamma Inverse Agonist. Mol Pharmacol. 2010 Feb;77(2):228-36.
3481 Mingming Gao, et al. The Liver X Receptor Agonist T0901317 Protects Mice From High Fat Diet-Induced Obesity and Insulin Resistance. AAPS J. 2013 Jan;15(1):258-66.
3482 Chem Ind 22:721 (1988)
3483 Prickaerts J, et al. EVP-6124, a novel and selective α7 nicotinic acetylcholine receptor partial agonist, improves memory performance by potentiating the acetylcholine response of α7 nicotinic acetylcholine receptors. Neuropharmacology. 2012 Feb;62(2):109
3484 Thomas Papouin, et al. Septal Cholinergic Neuromodulation Tunes the Astrocyte-Dependent Gating of Hippocampal NMDA Receptors to Wakefulness. Neuron. 2017 May 17;94:1-15.
3485 Papouin T, et al. Septal Cholinergic Neuromodulation Tunes the Astrocyte-Dependent Gating of Hippocampal NMDA Receptors to Wakefulness. Neuron. 2017 May 17;94(4):840-854.e7.
3486 Maehara S, et al. Pharmacological characterization of a novel potent, selective, and orally active phosphodiesterase 2A inhibitor, PDM-631. Eur J Pharmacol. 2017 Sep 15;811:110-116.
3487 Xiao B, et al. Structural basis of AMPK regulation by small molecule activators. Nat Commun. 2013;4:3017.
3488 Bultot L, et al. Benzimidazole derivative small-molecule 991 enhances AMPK activity and glucose uptake induced by AICAR or contraction in skeletal muscle. Am J Physiol Endocrinol Metab. 2016 Oct 1;311(4):E706-E719.
3489 Lumateperone
3490 Takasu T, et al. Effect of (R)-2-(2-aminothiazol-4-yl)-4'-{2-[(2-hydroxy-2-phenylethyl)amino]ethyl} acetanilide (YM178), a novel selective beta3-adrenoceptor agonist, on bladder function. J Pharmacol Exp Ther. 2007 May;321(2):642-7.
3491 C Brown , et al. The Monoamine Oxidase Inhibitor-Tyramine Interaction. J Clin Pharmacol. 1989 Jun;29(6):529-32.
3492 Gao Y, et al. Overcoming Resistance to the THZ Series of Covalent Transcriptional CDK Inhibitors. Cell Chem Biol. 2018 Feb 15;25(2):135-142.e5.
3493 Phytochemistry 21: 1063 (1982); Planta Medica 58: 389 (1992)
3494 Kemp JA, et al. 7-Chlorokynurenic acid is a selective antagonist at the glycine modulatory site of the N-methyl-D-aspartate receptor complex. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6547-50.
3495 Yaksh TL, et al. Characterization of the Effects of L-4-Chlorokynurenine on Nociception in Rodents. J Pain. 2017 Oct;18(10):1184-1196.
3496 Croucher MJ, et al. 7-Chlorokynurenic acid, a strychnine-insensitive glycine receptor antagonist, inhibits limbic seizurekindling. Neurosci Lett. 1990 Oct 2;118(1):29-32.
3497 Takahiro Horinouchi, et al. Different Changes of Plasma Membrane Beta-Adrenoceptors in Rat Heart After Chronic Administration of Propranolol, Atenolol and Bevantolol. Life Sci. 2007 Jul 12;81(5):399-404.
3498 M Takita, et al. Selectivity of Bevantolol Hydrochloride Towards Alpha- And Beta-Adrenoceptor Subtypes in Rat Cerebral Cortex. Jpn J Pharmacol. 1992 Feb;58(2):193-6.
3499 Soderholm JF, et al. Importazole, a small molecule inhibitor of the transport receptor importin-β. ACS Chem Biol. 2011 Jul 15;6(7):700-8.
3500 Yan WQ, et al. Effect of nuclear receptor inhibitor importazole on the proliferation and apoptosis of multiple myeloma cells. Zhonghua Xue Ye Xue Za Zhi. 2013 Apr;34(4):323-6.
3501 https://clinicaltrials.gov/ct2/show/NCT04591210?term=Enalapril&cond=covid&draw=1&rank=2
3502 N Z Med J 96:590 (1983); Rinsho Ketsueki 33:823 (1992); Rev Med Interne 17:859 (1996)
3503 Zhai D, et al. Gambogic acid is an antagonist of antiapoptotic Bcl-2 family proteins. Mol Cancer Ther. 2008 Jun;7(6):1639-46.
3504 Wang LH, et al. Gambogic acid synergistically potentiates cisplatin-induced apoptosis in non-small-cell lung cancer through suppressing NF-κB and MAPK/HO-1 signalling. Br J Cancer. 2014 Jan 21;110(2):341-52. |Tetrahedron 21: 1453 (1965); J Chem Soc(C) 1966:772; Tet Lett 1967:4201; Phytochemistry 41,: 815 (1996)
3505 Moret C, et al. Biochemical profile of midalcipran (F 2207), 1-phenyl-1-diethyl-aminocarbonyl-2-aminomethyl-cyclopropane (Z) hydrochloride, a potential fourth generation antidepressant drug. Neuropharmacology. 1985 Dec;24(12):1211-9.
3506 Briley M, et al. Preclinical pharmacology of milnacipran. Int Clin Psychopharmacol. 1996 Sep;11 Suppl 4:9-14.
3507 Punekar NS, et al. Acetylcholinesterase inhibition by pitofenone: a spasmolytic compound. Biotechnol Appl Biochem. 1991 Dec;14(3):378-82.
3508 Bull Chem Soc Jpn 29:419 (1956)
3509 S. David Brown , et al. (sulfinyl and sulfonyl benzimidazolyl) pyrimidines and triazines, pharmaceutical compositions thereof, and their use for treating proliferative diseases. WO2014055647A1
3510 J Nat Prod 49:690 (1986)
3511 Hong X, et al. In Vitro Glucuronidation of Wushanicaritin by Liver Microsomes, Intestine Microsomes and Expressed Human UDP-Glucuronosyltransferase Enzymes. Int J Mol Sci. 2017 Sep 19;18(9). pii: E1983.
3512 https://clinicaltrials.gov/ct2/show/NCT04865029?term=Estradiol&cond=COVID-19&draw=2&rank=1 https://clinicaltrials.gov/ct2/show/NCT04853069?term=Estradiol&cond=COVID-19&draw=2&rank=2 https://clinicaltrials.gov/ct2/show/NCT04359329?term=Estradiol&cond=COVID-19&draw=2&rank=3 https://clinicaltrials.gov/ct2/show/NCT04539626?term=Estradiol&cond=COVID-19&draw=2&rank=5 https://trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2020/09/027622
3513 Konze KD, et al. An Orally Bioavailable Chemical Probe of the Lysine Methyltransferases EZH2 and EZH1. ACS Chem Biol. 2013;8(6):1324-34.
3514 Corallo C, et al. Bosentan and macitentan prevent the endothelial-to-mesenchymal transition (EndoMT) in systemic sclerosis: in vitro study. Arthritis Res Ther. 2016 Oct 6;18(1):228.
3515 Sen S, et al. Renal, retinal and cardiac changes in type 2 diabetes are attenuated by macitentan, a dual endothelin receptor antagonist.&#x0D; Life Sci. 2012 Apr 13.
3516 Bruderer S, et al. Effect of cyclosporine and rifampin on the pharmacokinetics of macitentan, a tissue-targeting dual endothelin receptor antagonist.&#x0D; AAPS J. 2012 Mar;14(1):68-78.
3517 Kim SJ, et al. Antivascular therapy for multidrug-resistant ovarian tumors by macitentan, a dual endothelin receptor antagonist.&#x0D; Transl Oncol. 2012 Feb;5(1):39-47.
3518 Ihle NT, et al. The phosphatidylinositol-3-kinase inhibitor PX-866 overcomes resistance to the epidermal growthfactor receptor inhibitor ZD1839 in A-549 human non-small cell lung cancer xenografts. Mol Cancer Ther. 2005 Sep;4(9):1349-57.
3519 Bowles DW, et al. A Randomized, Phase II Trial of C225 With or Without PX-866, an Irreversible Oral Phosphatidylinositol 3-Kinase Inhibitor, in Patients With Metastatic Colorectal Carcinoma. Clin Colorectal Cancer. 2016 Dec;15(4):337-344.e2.
3520 Sonolisib
3521 https://clinicaltrials.gov/ct2/show/NCT04533347?term=Tafenoquine&cond=Covid19&draw=2&rank=1; https://trialsearch.who.int/Trial2.aspx?TrialID=NCT04533347
3522 Kazuhiro Miwa, et al. Discovery of 1-{4-[1-(2,6-Difluorobenzyl)-5-[(dimethylamino)methyl]-3-(6-methoxypyridazin-3-yl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl]phenyl}-3-methoxyurea (TAK-385) as a Potent, Orally Active, Non-Peptide Antagonist of the Human Gonadotropin-Releasing Hormone Receptor. doi/10.1021/jm200216q
3523 Daisuke Nakata, et al. Suppression of the hypothalamic-pituitary-gonadal axis by TAK-385 (relugolix), a novel, investigational, orally active, small molecule gonadotropin-releasing hormone (GnRH) antagonist: studies in human GnRH receptor knock-in mice. Eur J Pharmacol. 2014 Jan 15;723:167-74.
3524 JACS 62:869 (1910), J Org Chem 38:3729 (1973)
3525 Proc. Soc. Exp. Biol. Med. (1962), 109, 664-8; J. Org. Chem. (1961), 26, 2378-83; Scand. J. Gastroenterol. (1978), 13(3), 321-3
3526 Mandema JW, et al. Model-based development of gemcabene, a new lipid-altering agent. AAPS J. 2005 Oct 7;7(3):E513-22.
3527 Srivastava RAK, et al. Gemcabene, a First-in-Class Hypolipidemic Small Molecule in Clinical Development, Attenuates Osteoarthritis and Pain in Animal Models of Arthritis and Pain. Front Pharmacol. 2018 May 11;9:471.
3528 Oniciu DC, et al. Gemcabene downregulates inflammatory, lipid-altering and cell-signaling genes in the STAM™ model of NASH. PLoS One. 2018 May 30;13(5):e0194568.
3529 Molinoff PB, et al. PT-141: a melanocortin agonist for the treatment of sexual dysfunction. Ann N Y Acad Sci. 2003 Jun;994:96-102.
3530 Pfaus JG, et al. Selective facilitation of sexual solicitation in the female rat by a melanocortin receptor agonist. Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):10201-4.
3531 Barrett TD, et al. Pharmacological characterization of 1-(5-chloro-6-(trifluoromethoxy)-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid (JNJ-42041935), a potent and selective hypoxia-inducible factor prolyl hydroxylase inhibitor. Mol Pharmacol. 2011
3532 Tong J, et al. Antidepressant effect of helicid in chronic unpredictable mild stress model in rats. Int Immunopharmacol. 2019 Feb;67:13-21.
3533 Int J Immunopharmacol 14:505 (1992); Lancet 348:519 (1996)
3534 Draoui N, et al. Antitumor activity of 7-aminocarboxycoumarin derivatives, a new class of potent inhibitors of lactate influx but not efflux. Mol Cancer Ther. 2014 Jun;13(6):1410-8.
3535 Dutil L, et al. Ceftiofur resistance in Salmonella enterica serovar Heidelberg from chicken meat and humans, Canada. Emerg Infect Dis. 2010 Jan;16(1):48-54.
3536 Yancey RJ Jr, et al. Ceftiofur sodium, a broad-spectrum cephalosporin: evaluation in vitro and in vivo in mice. Am J Vet Res. 1987 Jul;48(7):1050-3.
3537 Salmon SA, et al. In vitro activity of ceftiofur and its primary metabolite, desfuroylceftiofur, against organisms of veterinary importance. J Vet Diagn Invest. 1996 Jul;8(3):332-6.
3538 https://clinicaltrials.gov/ct2/show/NCT04500639?term=Ibuprofen&cond=Covid19&draw=2&rank=1
3539 Knutson SK, et al. A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells. Nat Chem Biol. 2012;8(11):890-6.
3540 Tang SH, et al. Effects of H3K27 methylation inhibitor EPZ005687 on apoptosis, proliferation and cell cycle of U937 cells and normal CD34 positive cells. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2014 Dec;22(6):1561-6.
3541 Sangodkar J, et al. Activation of tumor suppressor protein PP2A inhibits KRAS-driven tumor growth. J Clin Invest. 2017 Jun 1;127(6):2081-2090.
3542 https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=ARGININE&cntry=&state=&city=&dist=
3543 Urwyler S, Campbell E, Fricker G, Biphenyl-derivatives of 2-amino-7-phosphono-heptanoic acid, a novel class of potent competitive N-methyl-D-aspartate receptor antagonists--II. Pharmacological characterization in vivo. Neuropharmacology. 1996 Jun;35(6):655-69.
3544 Gilmour G, et al. In vitro characterisation of the novel positive allosteric modulators of the mGlu₅ receptor, LSN2463359 and LSN2814617, and their effects on sleep architecture and operant responding in the rat. Neuropharmacology. 2013 Jan;64:224-39.
3545 Moore JD, et al. VER-246608, a novel pan-isoform ATP competitive inhibitor of pyruvate dehydrogenase kinase, disrupts Warburg metabolism and induces context-dependent cytostasis in cancer cells. Oncotarget. 2014 Dec 30;5(24):12862-76.
3546 Sharlow ER, et al. Potent and selective disruption of protein kinase D functionality by a benzoxoloazepinolone. J Biol Chem. 2008 Nov 28;283(48):33516-26.
3547 Venardos K, et al. The PKD inhibitor CID755673 enhances cardiac function in diabetic db/db mice. PLoS One. 2015 Mar 23;10(3):e0120934.
3548 Engers DW, et al. Synthesis and structure-activity relationships of a novel and selective bone morphogenetic protein receptor (BMP) inhibitor derived from the pyrazolo[1.5-a]pyrimidine scaffold of dorsomorphin: the discovery of ML347 as an ALK2 versus ALK3 selective MLPCN probe. Bioorg Med Chem Lett. 2013 Jun 1;23(11):3248-52.
3549 Whitley, R., et al., Vidarabine: a preliminary review of its pharmacological properties and therapeutic use. Drugs, 1980. 20(4): p. 267-82.
3550 Suzuki M, et al. Synergistic antiviral activity of acyclovir and vidarabine against herpes simplex virus types 1 and 2 and varicella-zoster virus. Antiviral Res. 2006;72(2):157-161. |Antimicrob Agents Chemother 1968:136, 180; Pharmacol Ther 8:143 (1980)
3551 https://clinicaltrials.gov/ct2/show/NCT04542850?term=AMINOLEVULINIC+ACID&cond=Covid19&draw=2&rank=2
3552 Chem Pharm Bull 25:1335 (1977; Arzniem) Forsch 19:5 (1968)
3553 J Steroid Biochem 20:945 (1984)
3554 Drugs (1999), 57(2), 261-277; Eur. J. Clin. Pharmacol. (1990), 38(Suppl. 1), S35-S51; J. Pharmacol. Exp. Ther. (1972), 180(3), 732-42
3555 Xu J, et al. Safety, pharmacokinetics, pharmacodynamics, and bioavailability of GSK2018682, a sphingosine-1-phosphate receptor modulator, in healthy volunteers. Clin Pharmacol Drug Dev. 2014 May;3(3):170-8.
3556 Tetrahedron 21: 1453 (1965)
3557 Arzneim Forsch 17:242 (1967); Curr Ther Res 9:537 (1967); 19:51 (1976)
3558 Ill Med J 119:398 (1961); Am J Psychiat 123:1303 (1967); Schizophr Res 53:25 (2002); Schizophr Bull 33:1379 (2007)
3559 J Chem Soc 1928:1504; Arch Pharmacal Res 21:140, 774 (1998); Eur J Pharmacol 513:237 (2005); World Acad Sci Eng Tech 60:215 (2011)|
3560 Dapson RW, et al. Brazilwood, sappanwood, brazilin and the red dye brazilein: from textile dyeing and folk medicine to biological staining and musical instruments. Biotech Histochem. 2015;90(6):401-23.
3561 Jia Y, et al. [Effect of brazilin on apoptosis and autophagy of tongue cancer Tca8113 cells and its molecular mechanism]. Nan Fang Yi Ke Da Xue Xue Bao. 2019 Mar 30;39(3):351-356.
3562 Weinmann D, et al, Brazilin blocks catabolic processes in human osteoarthritic chondrocytes via inhibition of NFKB1/p50. J Orthop Res. 2018 Sep;36(9):2431-2438.
3563 Miana M, et al. The lysyl oxidase inhibitor β-aminopropionitrile reduces body weight gain and improves the metabolic profile in diet-induced obesity in rats. Dis Model Mech. 2015 Jun;8(6):543-51.
3564 Yang X, et al. Inactivation of lysyl oxidase by β-aminopropionitrile inhibits hypoxia-induced invasion and migration of cervical cancer cells. Oncol Rep. 2013 Feb;29(2):541-8.
3565 Doi K, et al. Discovery of marinopyrrole A (maritoclax) as a selective Mcl-1 antagonist that overcomes ABT-737 resistance by binding to and targeting Mcl-1 for proteasomal degradation. J Biol Chem. 2012 Mar 23;287(13):10224-35.
3566 Haste NM, et al. Pharmacological properties of the marine natural product marinopyrrole A against methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2011 Jul;55(7):3305-12.
3567 Gomez-Bougie P, et al. The selectivity of Marinopyrrole A to induce apoptosis in MCL1high BCL2low expressing myeloma cells is related to its ability to impair protein translation. Br J Haematol. 2016 Aug 14.
3568 Eichhorn JM, et al. Purported Mcl-1 inhibitor marinopyrrole A fails to show selective cytotoxicity for Mcl-1-dependent cell lines. Cell Death Dis. 2013 Oct 24;4:e880
3569 J Pharm Pharmacol 23:848 (1971); J Allergy Clin Immunol 77:326 (1986)
3570 Mangeng Cheng, et al. CEP-28122, a highly potent and selective orally active inhibitor of anaplastic lymphoma kinase with antitumor activity in experimental models of human cancers. Mol Cancer Ther. 2012 Mar;11(3):670-9.
3571 Hawkins JL, et al. Pharmacologic inhibition of site 1 protease activity inhibits sterol regulatory element-binding protein processing and reduces lipogenic enzyme gene expression and lipid synthesis in cultured cells and experimental animals. J Pharmacol Exp Ther. 2008 Sep;326(3):801-8.
3572 Uchida L, et al. Suppressive Effects of the Site 1 Protease (S1P) Inhibitor, PF-429242, on Dengue Virus Propagation. Viruses. 2016 Feb 10;8(2). pii: E46. doi: 10.3390/v8020046.
3573 Urata S, et al. Antiviral activity of a small-molecule inhibitor of arenavirus glycoprotein processing by the cellular site 1 protease. J Virol. 2011 Jan;85(2):795-803.
3574 Fong TA, et al. SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization, and growth of multiple tumor types. Cancer Res, 1999, 59(1), 99-106.
3575 Vajkoczy P, et al. Inhibition of tumor growth, angiogenesis, and microcirculation by the novel Flk-1 inhibitor SU5416 as assessed by intravital multi-fluorescence videomicroscopy. Neoplasia, 1999, 1(1), 31-41.
3576 Happé CM, et al. Pneumonectomy combined with SU5416 induces severe pulmonary hypertension in rats.Am J Physiol Lung Cell Mol Physiol. 2016 Jun 1;310(11):L1088-97.
3577 Izquierdo-Garcia JL, et al. Metabolic Reprogramming in the Heart and Lung in a Murine Model of Pulmonary Arterial Hypertension. Front Cardiovasc Med. 2018 Aug 15;5:110.
3578 Zi D, et al. Danusertib Induces Apoptosis, Cell Cycle Arrest, and Autophagy but Inhibits Epithelial to Mesenchymal Transition Involving PI3K/Akt/mTOR Signaling Pathway in Human Ovarian Cancer Cells. Int J Mol Sci. 2015 Nov 13;16(11):27228-51.
3579 Gontarewicz A, et al. Simultaneous targeting of Aurora kinases and Bcr-Abl kinase by the small molecule inhibitor PHA-739358 is effective against imatinib-resistant BCR-ABL mutations including T315I. Blood. 2008 Apr 15;111(8):4355-64.
3580 Fraedrich K, et al. Targeting Aurora Kinases with Danusertib (PHA-739358) Inhibits Growth of Liver Metastases from Gastroenteropancreatic Neuroendocrine Tumors in an Orthotopic Xenograft Model. Clin Cancer Res. 2012 Sep 1;18(17):4621-32. Epub 2012 Jul 2.
3581 Lee HJ, et al. The influence of probiotic treatment on sulfasalazine metabolism in rat. Xenobiotica. 2012 Aug;42(8):791-7.
3582 Morini G, et al. Morphological features of rat gastric mucosa after acute and chronic treatment with amtolmetin guacyl: comparison with non-selective and COX-2-selective NSAIDs. Digestion. 2003;68(2-3):124-32. Epub 2003 Nov 7.
3583 Etcheverry SB, et al. Three new vanadyl(IV) complexes with non-steroidal anti-inflammatory drugs (Ibuprofen, Naproxen and Tolmetin). Bioactivity on osteoblast-like cells in culture. J Inorg Biochem. 2002 Jan 1;88(1):94-100.
3584 Dairam A, et al. Non-steroidal anti-inflammatory agents, tolmetin and sulindac, attenuate oxidative stress in rat brain homogenate and reduce quinolinic acid-induced neurodegeneration in rat hippocampal neurons. Metab Brain Dis. 2006 Sep;21(2-3):221-33.
3585 T D Warner, et al. Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis. Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7563-8.
3586 DADAŞ, Yakup, et al. Synthesis and anticancer activity of some novel tolmetin thiosemicarbazides. Marmara Pharmaceutical Journal 19(3) • April 2015
3587 Cho SD, et al. Nur77 agonists induce proapoptotic genes and responses in colon cancer cells through nuclear receptor-dependent and nuclear receptor-independent pathways. Cancer Res. 2007 Jan 15;67(2):674-83.
3588 David A, et al. Decreasing the Rate of Metabolic Ketone Reduction in the Discovery of a Clinical Acetyl-CoA Carboxylase Inhibitor for the Treatment of Diabetes. J Med Chem. 2014 Dec 26; 57(24): 10512–10526.
3589 Spierer O, et al. Comparative activity of antimicrobials against Pseudomonas aeruginosa, Achromobacter xylosoxidans and Stenotrophomonas maltophilia keratitis isolates. Br J Ophthalmol. 2018 May;102(5):708-712.
3590 J Chem Soc 1933:274
3591 Indian J Chem 15:94, 492 (1977)
3592 Wells E, et al. Characterization of primate bronchoalveolar mast cells. II. Inhibition of histamine, LTC4, and PGD2 release from primate bronchoalveolar mast cells and a comparison with rat peritoneal mastcells. J Immunol. 1986 Dec 15;137(12):3941-5.
3593 Myocardial remodeli