Kenakin Terry
Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
Curr Protoc Pharmacol. 2017 Mar 17;76:9.22.1-9.22.10. doi: 10.1002/cpph.18.
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.
七跨膜受体（7TMRs或G蛋白偶联受体[GPCRs]）是自然界中的典型变构蛋白，因为它们介导配体与受体结合以及受体与另一种细胞信号蛋白相互作用之间的联系。越来越多通过7TMRs起作用的潜在药物本质上是变构的，因为它们与受体蛋白上的一个单独位点结合，以改变受体、天然结合/正构配体和信号蛋白之间的相互作用。两种主要的变构化合物类别是那些增加（正变构调节剂[PAMs]）和那些减少（负变构调节剂[NAMs]）受体介导反应的化合物。本综述描述了用于测量和量化PAMs和NAMs与GPCRs相互作用的分子参数。© 2017约翰威立父子公司版权所有
