Draper-Joyce Christopher, Furness Sebastian George Barton
Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, Victoria, Australia.
ACS Pharmacol Transl Sci. 2019 Jul 26;2(4):285-290. doi: 10.1021/acsptsci.9b00054. eCollection 2019 Aug 9.
G protein-coupled receptors (GPCRs) are particularly attractive targets for therapeutic pharmaceuticals. This is because they are involved in almost all facets of physiology, in many pathophysiological processes, they are tractable due to their cell surface location, and can exhibit highly textured pharmacology. While the development of new drugs does not require the molecular details of the mechanism of activity for a particular target, there has been increasing interest in the GPCR field in these details. In part, this has come with the recognition that differential activity at a particular target might be a way in which to leverage drug activity, either through manipulation of efficacy or through differential coupling (signaling bias). To this end, the past few years have seen a number of publications that have specifically attempted to address one or more aspects of the molecular reaction pathway, leading to activation of heterotrimeric G proteins by GPCRs.
G蛋白偶联受体（GPCRs）是治疗药物特别有吸引力的靶点。这是因为它们几乎参与了生理学的各个方面，在许多病理生理过程中，由于其位于细胞表面，易于处理，并且可以表现出高度复杂的药理学特性。虽然新药的开发并不需要特定靶点活性机制的分子细节，但GPCR领域对这些细节的兴趣与日俱增。部分原因在于，人们认识到特定靶点的差异活性可能是一种利用药物活性的方式，无论是通过调节疗效还是通过差异偶联（信号偏向）。为此，在过去几年中，有许多出版物专门试图探讨分子反应途径的一个或多个方面，这些途径导致GPCRs激活异源三聚体G蛋白。
