Functional Assays as Prismatic Views of Drug Activity: Relevance to New Drug Discovery

REFERENCES

• De Lean A, Stadel J M, Lefkowitz R J. A ternary complex model explains the agonist-specific binding properties of the adenylate cyclase-coupled β -adrenergic receptor. J Biol Chem 1980; 255: 7108–7117
   PubMed Web of Science ®Google Scholar
• Samama P, Cotecchia S, Costa T, Lefkowitz R J. A mutation-induced activated state of the β2-adrenergic receptor: Extending the ternary complex model. J Biol Chem 1993; 268: 4625–4636
   PubMed Web of Science ®Google Scholar
• Weiss J M, Morgan P H, Lutz M W, Kenakin T P. The cubic ternary complex receptor-occupancy model. I. Model description. J Theor Biol 1996; 178: 151–167
   Web of Science ®Google Scholar
• Weiss J M, Morgan P H, Lutz M W, Kenakin T P. The cubic ternary complex receptor-occupancy model. II. Understanding apparent affinity J Theor Biol 1996; 178: 169–182
   Google Scholar
• Weiss J M, Morgan P H, Lutz M W, Kenakin T P. The cubic ternary complex receptor-occupancy model. III. Resurrecting efficacy. J Theor Biol 1996; 181: 381–397
   PubMed Web of Science ®Google Scholar
• Fraunfelder H, Parak F, Young R D. Conformational substrates in proteins. Annu Rev Biophys Biophys Chem 1988; 17: 451–479
   PubMedGoogle Scholar
• Fraunfelder H, Sligar S G, Wolynes P G. The energy landscapes and motions of proteins. Science 1991; 254: 1598–1603
   PubMed Web of Science ®Google Scholar
• Onaran H O, Costa T. Agonist efficacy and allosteric models of receptor action. Ann N Y Acad Sci 1997; 812: 98–115
   PubMed Web of Science ®Google Scholar
• Onaran H O, Scheer A, Cotecchia S, Costa T. A look at receptor efficacy. From the signaling network of the cell to the intramolecular motion of the receptor. The Pharmacology of Functional, Biochemical, and Recombinant Systems Handbook of Experimental Pharmacology, Vol. 148, T P Kenakin, J A Angus. Springer, HeidelbergGermany 2000; 217–280
   Google Scholar
• Burgen A SV. Conformational changes and drug action. Fed Proc 1966; 40: 2723–2728
   Google Scholar
• Kenakin T P. Efficacy at G protein coupled receptors. Annu Rev Pharmacol Toxicol 2002; 42: 349–379
   PubMedGoogle Scholar
• Kenakin T P. Efficacy at G protein coupled receptors. Nat Rev (Drug Discovery) 2002; 1: 103–109
   PubMed Web of Science ®Google Scholar
• Rees S, Morrow D, Kenakin T. GPCR drug discovery through the exploitation of allosteric drug binding sites. Recept Chann 2002; 8: 261–268
   PubMedGoogle Scholar
• Black J W, Leff P. Operational models of pharmacological agonist. Proc R Soc Lond [Biol], 1983; 220: 141–162
   PubMed Web of Science ®Google Scholar
• Kenakin T. P. Predicting therapeutic value in the lead optimization phase of drug discovery. Nat Rev Drug Discovery 2003; 2: 429–437
   PubMed Web of Science ®Google Scholar
• Azzi M, Charest P G, Angers S, Rousseau G, Kohout T, Bouvier M. β -arrestin-mediated activation of MAPK by inverse agonists reveals distinct active conformations for G-protein-coupled receptors. Proc Natl Acad Sci U SA 2003; 100: 11406–11411
   PubMed Web of Science ®Google Scholar
• Baker J G, Hall I P, Hill S J. Agonist and inverse agonist actions of β -blockers at the human β 2-adrenoceptor provide evidence for agonist-directed signaling. Mol Pharmacol 2003; 64: 1357–1369
   PubMed Web of Science ®Google Scholar
• Galandrin S, Bouvier M. Distinct signaling profiles of β1 and β2 adrenergic receptor ligands toward adenylyl cyclase and mitogen-activated protein kinase reveals the pluridimensionality of efficacy. Mol Pharmacol 2006; 70: 1575–1584
   PubMed Web of Science ®Google Scholar
• Copeland R A, Pompliano D L, Meek T D. Drug-target residence time and its implications for lead optimization. Nat Rev Drug Discovery 2006; 5: 730–739
   PubMed Web of Science ®Google Scholar
• Costa T, Herz A. Antagonists with negative intrinsic activity at β -opioid receptors coupled to GTP-binding proteins. Proc Natl Acad Sci U SA 1989; 86: 7321–7325
   PubMed Web of Science ®Google Scholar
• Gether U, Lin S, Kobilka B K. Fluorescent labeling of purified β2-adrenergic receptor. J Biol Chem 1995; 270: 28268–28275
   PubMed Web of Science ®Google Scholar
• Kenakin T P. Ligand-selective receptor conformations revisited: The promise and the problem. Trends Pharmacol. Sci. 2003; 24: 346–354
   Google Scholar
• Kenakin T P. Collateral efficacy in drug discovery: Taking advantage of the good (allosteric) nature of 7TM receptors. Trends Pharmacol Sci 2007; 28: 407–415
   PubMed Web of Science ®Google Scholar
• Urban J D, Clarke W P, Zastrow M, Nichols D E, Kobilka B, Weinstein H, et al. Functional selectivity and classical concepts of quantitative pharmacology. J Pharmacol Exp Ther 2007; 320: 1–13
   PubMed Web of Science ®Google Scholar
• Limbird L. The receptor concept: A continuing evolution. Mol Interv 2004; 4: 326–336
   PubMedGoogle Scholar
• Horne W C, Shyu J-F, Chakraborty M, Baron R. Signal transduction by calcitonin: Multiple ligands, receptors, and signaling pathways. Trends Endocrinol Metab 1994; 5: 395–401
   PubMedGoogle Scholar
• Watson C, Chen G, Irving P E, Way J, Chen W-J, Kenakin T P. The use of stimulus-biased assay systems to detect agonist-specific receptor active states: Implications for the trafficking of receptor stimulus by agonists. Mol. Pharmacol. 2000; 58: 1230–1238
   Google Scholar
• Kenakin T P. New concepts in drug discovery: Collateral efficacy and permissive antagonism. Nat Rev Drug Discovery 2005; 4: 919–927
   PubMed Web of Science ®Google Scholar
• Kenakin T P. Efficacy at G protein coupled receptors. Annu Rev Pharmacol Toxicol 2002; 42: 349–379
   PubMedGoogle Scholar
• Gesty-Palmer D, Chen M, Reiter E, Ahn S, Nelson C D, Wang S, et al. Distinct β -arrestin- and G protein-dependent pathways for parathyroid hormone receptor-stimulated ERK1/2 activation. J Biol Chem 2006; 281: 10856–10864
   PubMed Web of Science ®Google Scholar
• Maillet E L, Pellegrini N, Valant C, Bucher B, Hibert M B, Bourguignon J-J, Glazi J-L. A novel, conformation-specific allosteric inhibitor of the tachykinin NK2 receptor (NK2R) with functionally selective properties. FASEB J 2007; 21: 2124–2134
   PubMed Web of Science ®Google Scholar
• Sachpatzidis A, Benton B K, Manfredi J P, Wang H, Hamilton A, Dohlman H G, Loliset E. Identification of allosteric peptide agonists. J Biol Chem 2003; 278: 896–907
   PubMed Web of Science ®Google Scholar
• Mathiesen J M, Ulven T, Martini L, Gerlach L O, Heinemann A, Kosteniset E. Identification of indole derivatives exclusively interfering with a G protein-independent signaling pathway of the prostaglandin D2 receptor CRTH2. Mol Pharmacol 2005; 68: 393–402
   PubMed Web of Science ®Google Scholar
• Doranz B J, Lu Z H, Rucker J, Zhang T Y, Sharron M, Cen Y H, Wang Z H, Guo H H, Du J G, Accavitti M A, Doms R W, Peiper S C. Two distinct CCR5 domains can mediate coreceptor usage by human immunodeficiency virus type 1. J Virol 1997; 71: 6305–6314
   PubMed Web of Science ®Google Scholar
• Rucker J, Edinger A L, Sharron M, Samson M, Lee B, Berson J F, Yi Y, Margulies B, Collman R G, Doranz B J, Parmentier M, Doms R W. Utilization of chemokine receptors, orphan receptors, and herpesvirus-encoded receptors by diverse human and simian immunodeficiency viruses. J Virol 1997; 71: 8999–9007
   PubMed Web of Science ®Google Scholar
• Picard L, Simmons G, Power C A, Meyer A, Weiss R A, Clapham P R. Multiple extracellular domains of CCR-5 contribute to human immunodeficiency virus type 1 entry and fusion. J Virol 1997; 71: 5003–5011
   PubMed Web of Science ®Google Scholar
• Doms R W, Peiper S C. Unwelcomed guests with master keys: How H IVuses chemokine receptors for cellular entry. Virology 1997; 235: 179–190
   PubMed Web of Science ®Google Scholar
• Lee B, Sharron M, Blanpain C, Doranz B J, Vakili J, Setoh P, Berg E, Liu G, Guy H R, Durell S R, Parmentier M, Chang C N, Price K, Tsang M, Doms R W. Epitope mapping of CCR5 reveals multiple conformational states and distinct but overlapping structures involved in chemokine and coreceptor function. J Biol Chem 1999; 274: 9617–9626
   PubMed Web of Science ®Google Scholar
• Atchison R E, Gosling J, Monteclaro F S, Franci C, Digilio L, Charo I F, Goldsmith M A. Multiple extracellular elements of CCR5 and HIV-1 entry: Dissociation from response to chemokines. Science 1996; 274: 1924–1926
   PubMed Web of Science ®Google Scholar
• Smyth R J, Yi Y, Singh A, Collman R G. Determinants of entry cofactor utilization and Tropism in a dualtropic human immunodeficiency virus type 1 primary isolate. J Virol 1998; 72: 4478–4484
   PubMed Web of Science ®Google Scholar
• Bieniasz P D, Fridell R A, Aramori I, Ferguson S SG, Caron M G, Cullen B R. HIV-1-induced cell fusion is mediated by multiple regions within both the viral envelope and the CCR-5 co-receptor. EMBO J 1997; 16: 2599–2609
   PubMed Web of Science ®Google Scholar
• Kwong P D, Wyatt R, Robinson J, Sweet R W, Sodroski J, Hendrickson W A. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 1998; 393: 648–659
   PubMed Web of Science ®Google Scholar
• Kazmierski W, Peckham J P, Duan M, Kenakin T P, Jenkinson S, Gudmundsson K S, Piscitelli S C, Feldman P L. Recent progress in discovery of new CCR5 and CXCR4 chemokine receptor antagonists as inhibitors of HIV-1 entry. Part 2. Curr Med Chem Anti-Infective Agents 2005; 4: 2456–2472
   Google Scholar
• Kazmierski W M, Kenakin T P, Gudmundsson K S. Peptide, peptidomimetic and small-molecule drug discovery targeting HIV-1 host-cell attachment and entry through gp120, gp41, CCR5 and CXCR4. Chem Biol Drug Dis 2006; 67: 13–26
   PubMedGoogle Scholar
• Domingo E, Menendez-Arias L, Quinones-Mateu M E, Holguin A, Gutierrez Rivas M, Martinez M A, Quer J, Novella I S, Holland J J. Viral quasispecies and the problem of vaccine-escape and drug resistant mutants. Prog Drug Res 1997; 48: 99–128
   PubMedGoogle Scholar
• Harrigan P R, Bloor S, Larder B A. Relative replicative fitness of zidoviudine-resistant human immunodeficiency virus type 1 isolates in vitro. J Virol 1998; 72: 3773–3778
   PubMed Web of Science ®Google Scholar
• Schols D, Este J A, Cabrera C, De Clercq E. T-cell-line-tropic human immunodeficiency virus type 1 that is made resistant to stromal cell-derived factor 1-α contains mutations in the envelope gp120 but does not show a switch in coreceptor use. J. Virol. 1998; 72: 4032–4037
   Google Scholar
• Mosier M E, MoGastón D E, Picchio R, Gulizia R J, Sabbe R, Poignard P, Picard L, Offord R E, Thompson D A, Wilken J. Highly potent RANTES analogues either prevent CCR5-using human immunodeficiency virus type1 infection in vivo or rapidly select for CXCR4-using variants. J Virol 1999; 73: 3544–3550
   PubMed Web of Science ®Google Scholar
• Trkola A, Kuhmann S E, Strizki J M, Maxwell E, Ketas T, Morgan T, Pugach P, Xu S, Wojcik L, Tagat J, Palani A, Shapiro S, Clader J W, McCombie S, Reyes G R, Baroudy B M, Moore J P. HIV-1 escape from a small molecule, CCR5-specific entry inhibitor does not involve CXCR4 use. Proc Natl Acad Sci U SA 2002; 99: 395–400
   PubMed Web of Science ®Google Scholar
• Kenakin T P, Jenkinson S, Watson C. Determining the potency and molecular mechanism of action of insurmountable antagonists. J Pharmacol Exp Ther 2006; 319: 710–723
   PubMed Web of Science ®Google Scholar
• Jakubic J, Bacakova L, Lisa V, El-Fakahany E E, Tucek S. Positive cooperativity of acetylcholine and other agonists with allosteric ligands on muscarinic acetylcholine receptors. Mol Pharmacol 1997; 52: 172–179
   PubMedGoogle Scholar
• Xiang J, George S L, Wünschmann S, Chang Q, Klinzman D, Stapleton J T. Inhibition of HIV-1 replication by GB virus C infection through increases in RANTES, MlP-lα, MIP-1β, and SDF-1. Lancet 2004; 363: 2040–2046
   PubMed Web of Science ®Google Scholar
• Garzino-Demo A, Moss R B, Margolick J B, Cleghorn F, Sill A, Blattner W A, Cocchi F, Carlo D J, DeVico A L, Gallo R C. Spontaneous and antigen-induced production of HIV-inhibitory β -chemokines are associated with AIDS-free status. Proc Natl Acad Sci U SA 1999; 96: 11986–11991
   PubMedGoogle Scholar
• Heredia A, Davis C, Amoroso A, Dominique J K, Le N, Klingebiel E, Reardon E, Zella D, Redfield R R. Induction of G1 cycle arrest in T lymphocytes results in increased extracellular levels of β -chemokines: A strategy to inhibit R5 HIV-1. Proc Natl. Acad. Sci U SA 2003; 100: 4179–4184
   PubMed Web of Science ®Google Scholar
• Ullum H, Cozzi Lepri A C, Victor J, Aladdin H, Phillips A N, Gerstoft J, Skinho P-J, Pedersen B K. Production of β -chemokines in human immunodeficiency virus (HIV) infection: Evidence that high levels of macrophage inflammatory protein-1β are associated with a decreased risk of HIV disease progression. J Infect Dis 1998; 177: 331–337
   PubMedGoogle Scholar
• Lori F, Jessen H, Foli A, Lisziewicz J, Matteo P S. Long-term suppression of HIV-1 by hydroxyurea and didanosine. JAMA 1997; 277: 1437–1438
   PubMed Web of Science ®Google Scholar
• Rogez C, Martin M, Dereuddre-Bosquet N, Martal J, Dormont D, Clayette P. Anti-human immunodeficiency virus activity of tau interferon in human macrophages: Involvement of cellular factors and β -chemokines. J Virol 2003; 77: 12914–12920
   PubMedGoogle Scholar
• Gonzalez E, Kulkarni H, Bolivar H, Mangano A, Sanchez R, Catano G, Nibbs R J, Freedman B I, Quinones M P, Bamshad M J, Murthy K K, Rovin B H, Bradley W, Clark R A, Anderson S A, O'Connell R J, Agan B K, Ahuja S S, Bologna R, Sen L, Dolan M J, Ahuja S K. The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility. Science 2005; 310: 1434–1440
   Google Scholar
• Choi W-T, Kaul M, Kumar S, Wang J, Krishna Kumar I M, Dong C-Z, An J, Lipton S A, Huang Z. Neuronal apoptotic signaling pathways probed and intervened by synthetically and modularly modified (SMM) chemokines. J Biol Chem 2007; 282: 7154–7163
   PubMed Web of Science ®Google Scholar
• Kaul M, Lipton S A. Chemokines and activated macrophages in HIV gp120-induced neuronal apoptosis. Proc Natl Acad Sci U SA 1999; 96: 8212–8216
   PubMed Web of Science ®Google Scholar
• Tyner J W, Uchida O, Kajiwara N, Kim E Y, Patel A C, O'Sullivan M P, Walter M J, Schwendener R A, Cook D N, Danoff T M, Holtzman M J. CCL5-CCR5 interaction provides antiapoptotic signals for macrophage survival during viral infection. Nature Med 2005; 11: 1180–1187
   PubMed Web of Science ®Google Scholar
• Vhlahakis S R, Villasis-Keever A, Gomez T, Vanegas M, Vhlahakis N, Paya C V. G protein-coupled chemokine receptors induce both survival and apoptotic singaling pathways. J Immunol 2002; 169: 5546–5554
   PubMedGoogle Scholar