title: The Quantitative Characterization of Functional Allosteric Effects.
abstract: Seven-transmembrane receptors (7TMRs or GPCRs [G protein-coupled receptors]) are nature's prototypic allosteric proteins in that they mediate the interaction between ligand binding to the receptor and the receptor interacting with another cell signaling protein. A growing class of potential drugs acting through 7TMRs are allosteric in nature in that they bind to a separate site on the receptor protein to modify the interactions between the receptor, natural binding/orthosteric ligand, and signaling proteins. Two main allosteric compound categories are those that increase (positive allosteric modulators [PAMs]) and those that decrease (negative allosteric modulators [NAMs]) receptor-mediated responses. Described in this overview are the molecular parameters used to measure and quantify the interaction of PAMs and NAMs with GPCRs. © 2017 by John Wiley & Sons, Inc.
authors.affiliation: Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors.forename: Terry
authors.initials: T
authors.lastname: Kenakin
mesh_terms: D000494:Allosteric Regulation; D001665:Binding Sites; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D008024:Ligands; D011956:Receptors, Cell Surface / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D008024:Ligands; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled
keywords: allosteric; allosteric drugs; drug activity; quantifying drug activity