Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Melbourne, Victoria 3052, Australia.
Nat Rev Drug Discov. 2013 Aug;12(8):630-44. doi: 10.1038/nrd4052.
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.
变构配体在不同于内源性配体结合的位点与 G 蛋白偶联受体 (GPCR；也称为七跨膜受体) 结合。变构配体的存在丰富了操纵 GPCR 功能的方式，以获得潜在的治疗益处，但其作用的复杂性为药物筛选和开发提供了挑战和机遇。变构配体的偏信号传导等领域的研究途径不断汇聚，以及变构配体调节多种内源性配体效应的机制，为了解变构配体与 GPCR 之间的相互作用如何用于药物发现提供了新的见解。这些新发现有可能改变变构药物筛选的方式，并可能增加作为临床先导化合物的变构调节剂开发成功的机会。
