G-protein-coupled receptor allosterism: the promise and the problem(s).
Allosteric modulators of G-protein-coupled receptors interact with binding sites that are topographically distinct from the orthosteric site recognized by the receptor's endogenous agonist. Allosteric ligands offer a number of advantages over orthosteric drugs, including the potential for greater receptor subtype selectivity and a more 'physiological' regulation of receptor activity. However, the manifestations of allosterism at G-protein-coupled receptors are quite varied, and significant challenges remain for the optimization of screening methods to ensure the routine detection and validation of allosteric ligands.
Christopoulos
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Department of Pharmacology, University of Melbourne, Grattan St., Parkville, 3010, Victoria, Australia.
May
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LT
Avlani
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Sexton
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PM
D000443:Alcuronium / Q000494:pharmacology; D000495:Allosteric Site; D000818:Animals; D001665:Binding Sites; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008956:Models, Chemical; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction
D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D000443:Alcuronium