Qualitative pharmacology in a quantitative world: Diminishing value in the drug discovery process

Current Opinion in Pharmacology

Volumn 11, Issue 5, 2011, Pages 496-500

  Williams, Michael ^a  

^a NORTHWESTERN UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 (5 CHLORO 2 INDOLYLCARBONYL) 4 METHYLPIPERAZINE; 2 MORPHOLINO 8 PHENYLCHROMONE; ADENYLATE KINASE; BETA ARRESTIN; CALCIUM CHANNEL; DOPAMINE 1 RECEPTOR; DORSOMORPHIN; ENZYME INHIBITOR; EPIDERMAL GROWTH FACTOR RECEPTOR; GUANINE NUCLEOTIDE BINDING PROTEIN; NALOXONE; PHOSPHATIDYLINOSITOL 3 KINASE; PLATELET DERIVED GROWTH FACTOR RECEPTOR; PURINERGIC P2Y2 RECEPTOR; RYANODINE RECEPTOR; SURAMIN; UNCLASSIFIED DRUG;

ANALGESIC ACTIVITY; APOPTOSIS; ARTICLE; CONCENTRATION RESPONSE; DOSE RESPONSE; DOWNSTREAM PROCESSING; DRUG DESIGN; DRUG EFFICACY; DRUG IDENTIFICATION; DRUG RECEPTOR BINDING; DRUG RESEARCH; DRUG SAFETY; DRUG SYNTHESIS; HIGH THROUGHPUT SCREENING; HUMAN; NONHUMAN; NULL HYPOTHESIS; ONCHOCERCIASIS; PHARMACOLOGICAL SCIENCE; PRACTICE GUIDELINE; PRIORITY JOURNAL; PROTEIN SYNTHESIS INHIBITION; QUALITATIVE RESEARCH; QUANTITATIVE STUDY; TRYPANOSOMIASIS;

EID: 80053096991     PISSN: 14714892     EISSN: 14714973     Source Type: Journal    
DOI: 10.1016/j.coph.2011.04.002     Document Type: Review

References (29)

1. B. Munos Lessons from 60 years of pharmaceutical innovation Nat Rev Drug Discov 8 2009 959 968
2. S.J. Enna, and M. Williams Challenges in the search for drugs to treat central nervous system disorders J Pharmacol Exp Ther 329 2009 404 411
3. M. Lindner Clinical attrition due to biased preclinical assessments of potential efficacy Pharmacol Ther 115 2007 148 175 (Pubitemid 46992811)
4. D.G. Flood, G.M. Marek, and M. Williams Developing predictive CSF Biomarkers - a challenge critical to success in Alzheimer's disease and neuropsychiatric translational medicine Biochem Pharmacol 2011 10.1016/j.bcp.2011.01.021
5. J.P. Evans, E.M. Meslin, T.M. Marteu, and T. Cauldield Deflating the genomic bubble Science 331 2011 861 862
6. K.K. Kopec, D. Bozyczko-Coyne, and M. Williams Target identification and validation in drug discovery: the role of proteomics Biochem Pharmacol 69 2005 1133 1139 (Pubitemid 40417484)
7. T.I. Oprea, C.G. Bologa, S. Boyer, R.F. Curpan, R.C. Glen, A.L. Hopkins, C.A. Lipinski, G.A. Marshall, Y.C. Martin, and L. Ostopovici-Halip A crowdsourcing evaluation of the NIH chemical probes Nat Chem Biol 5 2009 441 447
8. R. Macarron, M.N. Banks, D. Bojanic, D.J. Burns, D.A. Cirovic, T. Garyantes, D.V. Green, R.P. Hertzberg, W.P. Janzen, and J.W. Paslay Impact of high-throughput screening in biomedical research Nat Rev Drug Discov 10 2011 188 195
9. M.A. Ator, J.P. Mallamo, and M. Williams Overview of drug discovery and development Curr Protoc Pharmacol 35 2006 9.9.1-9.9.27
10. C.A. Lipinski, F. Lombardo, B.W. Dominy, and P.J. Feeney Experimental, computational approaches to estimate solubility and permeability in drug discovery and development settings Adv Drug Deliv Rev 46 2001 3 26 (Pubitemid 33653411)
11. M. Rowland, C. Peck, and G. Tucker Physiologically-based pharmacokinetics in drug development and regulatory science Annu Rev Pharmacol Toxicol 51 2011 45 73
12. M.P. Gleeson, A. Hersey, D. Montanari, and J. Overington Probing the links between in vitro potency. ADMET and physicochemical parameters Nat Rev Drug Discov 10 2011 197 208
13. F. Sams-Dodd Research and market strategy: how choice of drug discovery approach can affect market position Drug Discov Today 12 2007 314 318 (Pubitemid 46467487)
14. M. Williams Productivity shortfalls in drug discovery: contributions from the preclinical sciences? J Pharmacol Exp Ther 336 2011 3 8
15. 2 purinoceptor from human erythroleukemia cells J Biol Chem 271 1996 18363 18367 (Pubitemid 26322690)
16. C.L. Herold, Q. Qing Li, B. Joel, J.B. Schachter, T.K. Harden, and R.A. Nicholas Lack of nucleotide-promoted second messenger signaling responses in 1321N1 cells expressing the proposed P2Y receptor, p2y7 Biochem Biophys Res Commun 235 1997 717 721 (Pubitemid 27326550)
17. T. Yokomizo, T. Izumi, K. Chang, Y. Takuwa, and T. Shimizu A G-protein-coupled receptor for leukotriene B4 that mediates chemotaxis Nature 387 1997 620 624 (Pubitemid 27248768)
18. T.P. Kenakin A Pharmacology Primer edn 3 2009 Academic Press Burlington, MA
19. C.J. Viahos, W.F. Matter, K.Y. Hui, and R.F. Brown A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-l-benzopyran-4- one (LY294002) J Biol Chem 269 1994 5241 5248
20. J. Wu, W.-G. Ding, H. Matsuura, K. Tsuji, W.-J. Zang, and M. Horie Inhibitory actions of the phosphatidylinositol 3-kinase inhibitor LY294002 on the human Kv1.5 channel Br J Pharmacol 156 2009 377 387
21. G. Lambrecht, K. Braun, S. Damer, M. Ganso, C. Hildebrandt, H. Ullmann, M.U. Kassack, and P. Nickel Structure-activity relationships of suramin and pyridoxal-5′-phosphate derivatives as P2 receptor antagonists Curr Pharm Des 2002 2371 2399 (Pubitemid 35339325)
22. F. Freissmuth, S. Boehm, W. Beindl, P. Nickel, A.P. IJzerman, M. Hohenegger, and C. Nanoff Suramin analogues as subtype-selective G protein inhibitors Mol Pharmacol 49 1996 602 611 (Pubitemid 26117644)
23. M.-H. Hsu, U. Savas, J.M. Lasker, and E.F. Johnson Genistein, resveratrol and AICAR induce cytochrome P450 4F2 expression through an AMP-activated protein kinase-dependent pathway J Pharmacol Exp Ther 2011 10.1124/jpet.110. 175851
24. J. Hao, M.A. Daleo, C.K. Murphy, P.B. Yu, J.N. Ho, J. Hu, R.T. Peterson, A.K. Hatzopoulos, and C.C. Hong Dorsomorphin, a selective small molecule inhibitor of BMP signaling, promotes cardiomyogenesis in embryonic stem cells PLoS One 3 2008 e2904
25. P.B. Yu, C.C. Hong, C. Sachidanandan, J.L. Babitt, D.Y. Deng, S.A. Hoyng, H.Y. Lin, K.D. Bloch, and R.T. Peterson Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism Nat Chem Biol 4 2008 33 41 (Pubitemid 350273653)
26. C.L. Schmid, and L.M. Bohn Serotonin, but not N-methyltryptamines, activates the serotonin 2A receptor via a β-arrestin2/Src/Akt signaling complex in vivo J Neurosci 30 2010 13513 13524
27. E.M. Rosethorne, and S.J. Charlton Agonist-biased signaling at the histamine H4 receptor: JNJ7777120 recruits beta-arrestin without activating G proteins Mol Pharmacol 2011 10.1124/mol.110.068395
28. N.M. Urs, T.L. Daigle, and M.G. Caron A dopamine D1 receptor-dependent β-arrestin signaling complex potentially regulates morphine-Induced psychomotor activation but not reward in mice Neuropsychopharmacology 36 2011 551 558
29. T. Kenakin, and O. Onaran The ligand paradox between affinity and efficacy: can you be there and not make a difference? Trends Pharmacol Sci 23 2002 275 280 (Pubitemid 34655733)