title: G-protein-coupled receptor allosterism: the promise and the problem(s).
abstract: 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.
authors.affiliation: Department of Pharmacology, University of Melbourne, Grattan St., Parkville, 3010, Victoria, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Christopoulos
authors.forename: L T
authors.initials: LT
authors.lastname: May
authors.forename: V A
authors.initials: VA
authors.lastname: Avlani
authors.forename: P M
authors.initials: PM
authors.lastname: Sexton
mesh_terms: 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
chemical_list: D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D000443:Alcuronium