title: Emerging paradigms in GPCR allostery: implications for drug discovery.
abstract: Allosteric ligands bind to G protein-coupled receptors (GPCRs; also known as seven-transmembrane receptors) at sites that are distinct from the sites to which endogenous ligands bind. The existence of allosteric ligands has enriched the ways in which the functions of GPCRs can be manipulated for potential therapeutic benefit, yet the complexity of their actions provides both challenges and opportunities for drug screening and development. Converging avenues of research in areas such as biased signalling by allosteric ligands and the mechanisms by which allosteric ligands modulate the effects of diverse endogenous ligands have provided new insights into how interactions between allosteric ligands and GPCRs could be exploited for drug discovery. These new findings have the potential to alter how screening for allosteric drugs is performed and may increase the chances of success in the development of allosteric modulators as clinical lead compounds.
authors.affiliation: Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Melbourne, Victoria 3052, Australia.
authors.forename: Denise
authors.initials: D
authors.lastname: Wootten
authors.forename: Arthur
authors.initials: A
authors.lastname: Christopoulos
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Sexton
mesh_terms: D000494:Allosteric Regulation; D000495:Allosteric Site; D000818:Animals; D055808:Drug Discovery / Q000379:methods*; D015507:Drugs, Investigational / Q000494:pharmacology; D057166:High-Throughput Screening Assays; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D058990:Molecular Targeted Therapy; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013045:Species Specificity
chemical_list: D015507:Drugs, Investigational; D008024:Ligands; D043562:Receptors, G-Protein-Coupled
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