The contribution of mechanistic understanding to phenotypic screening for first-in-class medicines

Journal of Biomolecular Screening

Volumn 18, Issue 10, 2013, Pages 1186-1192

  Swinney, David C ^a  

^a Institute for Rare and Neglected Diseases Drug Discovery   (United States)

Author keywords

cell based assays; ligand binding; pharmacology; phenotypic drug discovery; receptor binding; structure activity relationships

Indexed keywords

ANTICONVULSIVE AGENT; ARIPIPRAZOLE; AZACITIDINE; CASPOFUNGIN; CILOSTAZOL; CINACALCET; DAPTOMYCIN; ETIRACETAM; EZETIMIBE; GEFITINIB; GREEN TEA EXTRACT; IMATINIB; IVACAFTOR; LINEZOLID; MARAVIROC; MIGLUSTAT; NATEGLINIDE; NITISINONE; PEMIROLAST; PERAMPANEL; RALTEGRAVIR; RANOLAZINE; RUFINAMIDE; SORAFENIB; SUNITINIB; UNINDEXED DRUG; VISMODEGIB; VORINOSTAT; ZANAMIVIR; ZONISAMIDE;

ANTIMICROBIAL ACTIVITY; ARTICLE; CELL DIFFERENTIATION; CYTOTOXICITY; DNA METHYLATION; DRUG APPROVAL; DRUG DEVELOPMENT; DRUG IDENTIFICATION; DRUG SCREENING; FOLLOW UP; FOOD AND DRUG ADMINISTRATION; HUMAN; INFLAMMATION; MEDICINE; MOLECULAR BIOLOGY; MYCOBACTERIUM SMEGMATIS; PAIN; PHENOTYPE; PRIORITY JOURNAL; PROTEOMICS; UNITED STATES;

CELL-BASED ASSAYS; LIGAND BINDING; PHARMACOLOGY; PHENOTYPIC DRUG DISCOVERY; RECEPTOR BINDING; STRUCTURE-ACTIVITY RELATIONSHIPS;

ANIMALS; BIOLOGICAL ASSAY; DRUG APPROVAL; DRUG DISCOVERY; HUMANS; PHARMACOLOGICAL PHENOMENA; PHENOTYPE;

EID: 84887913784     PISSN: 10870571     EISSN: 1552454X     Source Type: Journal    
DOI: 10.1177/1087057113501199     Document Type: Article

References (44)

1. Swinney D. C., Anthony J.. How Were New Medicines Discovered?. Nat. Rev. Drug Discov. 2011 ; 10: 507-519
2. Swinney D. C.. Phenotypic vs. Target-Based Drug Discovery for First-in-Class Medicines. Clin. Pharmacol. Ther. 2013 ; 93: 299-301
3. Yasuda Y., Kikuchi T., Suzuki S., et al. 7-[3-[4-(2,3 Dimethylphenyl)piperazinyl] propoxy]-2(1H)-quinolinone (OPC-4392), a Presynaptic Dopamine Receptor Agonist and Postsynaptic D2 Receptor Antagonist. Life Sci. 1988 ; 42: 1941-1954
4. Salisbury B. G., Davis H. R., Burrier R. E., et al. Hypocholesterolemic Activity of a Novel Inhibitor of Cholesterol Absorption, SCH 48461. Atherosclerosis. 1995 ; 115: 45-63
5. Glower A. J., Noyer M., Verloes R., et al. UCB L059, a Novel Anti-Convulsant Drug: Pharmacological Profile in Animals. Eur. J. Pharmacol. 1992 ; 222: 193-203
6. Shinkai H., Toi K., Kumashiro I., et al. N-acylphenylanalines and Related Compounds: A New Class of Oral Hypoglycemic Agents. J. Med. Chem. 1988 ; 31: 2092-2097
7. Lock E. A., Ellis M. K., Gaskin P., et al. From Toxicological Problem to Therapeutic Use: The Discovery of the Mode of Action of 2-(2-Nitro-4- trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), Its Toxicology and Development as a Drug. J. Inher. Metab. Dis. 1998 ; 21: 498-506
8. Yanagihara Y., Kasai H., Kawashima T., et al. Immunopharmacological Studies on TBX, a New Antiallergic Drug (1): Inhibitory Effects on Passive Cutaneous Anaphylaxis in Rats and Guinea Pigs. Jpn. J. Pharmacol. 1988 ; 48: 91-101
9. Gaffney S. M.. Ranolazine, a Novel Agent for Chronic Stable Angina. Pharmacotherapy. 2006 ; 26: 135-142
10. Jain K. K.. An Assessment of Rufinamide as an Anti-Epileptic in Comparison with Other Drugs in Clinical Development. Expert Opin. Investig. Drugs. 2000 ; 9: 829-840
11. Valentino D., Newcomb R., Gadbois T., et al. A Selective N-type Calcium Channel Antagonist Protects against Neuronal Loss after Global Cerebral Ischemia. Proc. Natl. Acad. Sci. U. S. A. 1993 ; 90: 7894-7897
12. Masuda Y., Karasawa T., Hori M., et al. 3-Sulfamoylmethyl-1,2- benzisoxazole, a New Type of Anticonvulsant Drug: Pharmacological Profile. Arzneimittelforschung. 1980 ; 30: 477-483
13. Issa J. P. J., Kantarjian H. M., Kirkpatrick P.. Azacitidine. Nat. Rev. Drug Discov. 2005 ; 4: 275-276
14. Nishi T., Yamamoto K., Shimizu T., et al. Studies on 2-Oxoquinoline Derivatives as Blood Platelet Aggregation Inhibitors: I. Alkyl 4-(2-oxo-1,2,3,4-tetrahydro-6-quinolyloxy)butyrates and Related Compounds. Chem. Pharm. Bull. 1983 ; 31: 798-810
15. Tally F. P., DeBruin M. F.. Development of Daptomycin for Gram-Positive Infections. J. Antimicrob. Chemother. 2000 ; 46: 523-526
16. Katz D. H., Marcelletti J. F., Khalil M. H., et al. Antiviral Activity of 1-Docosanol, an Inhibitor of Lipid-Enveloped Viruses Including Herpes Simplex. Proc. Natl. Acad. Sci. U. S. A. 1991 ; 88: 10825-10829
17. Brickner S. J.. Oxazolidinone Antibacterial Agents. Curr. Pharm. Des. 1996 ; 2: 175-194
18. Gandhi V., Keating M. J., Bate G., et al. Nelarabine. Nat. Rev. Drug Discov. 2006 ; 5: 17-18
19. Rossignol J. F., Maisonneuve H.. Nitazoxanide in the Treatment of Teania saginata and Hymenolepis nana Infections. Am. J. Trop. Med. Hyg. 1984 ; 33: 511-512
20. Hunt E.. Pleuromutilin Antibiotics. Drugs Fut. 2000 ; 25: 1163-1168
21. Martel R. R., Klicius J., Galet S.. Inhibition of Immune Response by Rapamycin, a New Antifungal Antibiotic. Can. J. Physiol. Pharmacol. 1977 ; 55: 48-51
22. Marks P. A., Breslow R.. Dimethyl Sulfoxide to Vorinostat: Development of This Histone Deacetylase Inhibitor as an Anticancer Drug. Nat. Biotech. 2007 ; 25: 84-90
23. Bartizal K., Abruzzo G., Trainor C., et al. In Vitro Antifungal Activities and In Vivo Efficacies of 1,3-β-Glucan Synthesis Inhibitors L671,329, L646,991, Tetrahydroechinocandin B, and L687,781, a Papulacandin. Antimicrob. Agents Chemother. 1992 ; 36: 1648-1657
24. Nemeth E. F.. Misconceptions about Calcimimetics. Ann. N. Y. Acad. Sci. 2006 ; 1068: 471-476
25. Platt F. M., Neises G. R., Dwek R. A., et al. N-butyldeoxynojirimycin Is a Novel Inhibitor of Glycolipid Biosynthesis. J. Biol. Chem. 1994 ; 269: 8362-8365
26. Wakeling A. E., Dukes M., Bowler J.. A Potent Specific Pure Antiestrogen with Clinical Potential. Cancer Res. 1991 ; 51: 3867-3873
27. Coe J. E., Brooks P. R., Vetelino M. G., et al. Varenicline: An α4β2 Nicotinic Receptor Partial Agonist for Smoking Cessation. J. Med. Chem. 2005 ; 48: 3474-3477
28. Lipton S. A.. Paradigm Shift in Neuroprotection by NMDA Receptor Blockade: Memantine and Beyond. Nat. Rev. Drug Discov. 2006 ; 5: 160-170
29. Meltzer S. M., Monk B. J., Tewari K. S.. Green Tea Catechins for Treatment of External Genital Warts 2009. Am. J. Obstet. Gynecol 200.: 233.e1-233.e7
30. Tradtrantip L., Namkung W., Verkman A. S.. Crofelemer, an Antisecretory Antidiarrheal Proanthocyanidin Oligomer Extracted from Croton lechleri, Targets Two Distinct Intestinal Chloride Channels. Mol. Pharmacol. 2010 ; 77: 69-78
31. Wetzler M., Segal D.. Omacetaxine as an Anticancer Therapeutic: What Is Old Is New Again. Curr. Pharm. Des. 2011 ; 11: 59-64
32. Ogbourne S. M., Suhrbier A., Jones B., et al. Antitumor Activity of 3-Ingenyl Angelate: Plasma Membrane and Mitochondrial Disruption and Necrotic Cell Death. Cancer Res. 2004 ; 64: 2833-2839
33. Andries K., Verhasselt P., Guillemont J., et al. A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis. Science. 2005 ; 307: 223-227
34. Rogawski M. A.. Revisiting AMPA Receptors as an Antiepileptic Drug Target. Epilepsy Curr. 2011 ; 11: 56-63
35. Chen J. K., Taipale J., Young K. E., et al. Small Molecule Modulation of Smoothened Activity. Proc. Natl. Acad. Sci. U. S. A. 2002 ; 99: 14071-14076
36. Van Goor F., Straley K. S., Cao D., et al. Rescue of ΔF508-CFTR Trafficking and Gating in Human Cystic Fibrosis Airway Primary Cultures by Small Molecules. Am. J. Physiol. Lung Cell. Mol. Physiol. 2006 ; 290: L1117 - L1130
37. Black J.. Personal Perspective on Dr. Paul Janssen. J. Med. Chem. 2005 ; 48: 1687-1688
38. Mol. Interv. 2004 ; 4: 139-142
39. Boitano A. E., Wang J., Romeo R., et al. Aryl Hydrocarbon Receptor Antagonists Promote the Expansion of Human Hematopoietic Stem Cells. Science. 2010 ; 329: 1345-1348
40. Garcia-Calvo M., Lisnock J., Bull H. G., et al. The Target of Exetimibe Is Niemann-Pick C1-Like 1 (NPC1L1). Proc. Natl. Acad. Sci. U. S. A. 2005 ; 102: 8132-8137
41. Chung C., Costa H., White J. H., et al. Discovery and Characterization of Small Molecule Inhibitors of the BET Family Bromodomains. J. Med. Chem. 2011 ; 54: 3827-3838
42. Gregori-Puigjane E., Setola V., Hert J., et al. Identifying Mechanism-of-Action Targets for Drugs and Probes. Proc. Natl. Acad. Sci. U. S. A. 2012 ; 109: 11178-11183
43. Rihel J., Prober D. A., Arvanites A., et al. Zebrafish Behavioral Profiling Links Drugs to Biological Targets and Rest/Wake Regulation. Science. 2010 ; 327: 348-351
44. Schulze C. J., Bray W. M., Woerhmann M. H., et al. "Function- First" Lead Discovery: Mode of Action Profiling of Natural Product Libraries Using Image-Based Screening. Chem. Biol. 2013 ; 20: 285-295