title: Allosteric modulators of G-protein-coupled receptors.
abstract: Allosteric modulators of G-protein-coupled receptors (GPCRs) interact with binding sites on the receptor that are topographically distinct from the orthosteric site recognized by the receptor's endogenous agonist. Allosteric modulators offer several advantages over standard orthosteric drugs, including the potential for greater receptor subtype selectivity. To date, the current paucity of clinically available allosteric drugs reflects the bias of traditional radioligand binding assays towards the detection of orthosteric effects. However, the advent of new cell-based high-throughput functional assays has led to an increased detection of allosteric GPCR ligands. The current challenge for modulator-based GPCR drug discovery is the optimization of both binding and functional assays to better detect and validate allosteric ligands.
authors.affiliation: Department of Pharmacology, University of Melbourne, Victoria 3010, Australia.
authors.forename: Lauren T
authors.initials: LT
authors.lastname: May
authors.forename: Arthur
authors.initials: A
authors.lastname: Christopoulos
mesh_terms: D000494:Allosteric Regulation; D000495:Allosteric Site; D000818:Animals; D001667:Binding, Competitive; D015195:Drug Design; D006801:Humans; D008024:Ligands; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects* / Q000378:metabolism; D013678:Technology, Pharmaceutical / Q000639:trends
chemical_list: D008024:Ligands; D043562:Receptors, G-Protein-Coupled