别构调节G蛋白偶联受体及该受体别构调节剂研究

Pharmacological development of G protein-coupled receptors allosteric modulation

G蛋白偶联受体(GPCRs)介导多数激素及神经递质的细胞信号转导,同时也是最重要的药物作用靶点。相对于正位作用,对GPCRs别构调节具有能够达到高选择性、模拟生理性调制受体以及不易过度激活受体的特点而受到关注,A、B、C三族GPCRs均有别构调节剂被发现,有些已被用于临床。随着GPCRs别构理论研究的深入,若在别构调节剂开发策略指导下进行定向筛选和结构改造,将会获得更有前途的治疗药物。

G protein-coupled receptors （GPCRs）mediate cell signaling transduction of most hormones and neurological transmitters and behave as the key targets for drug research and development. Recently, the evidence of allosteric modulation of GPCRs has been revealed. Allosteric modulators have the ability to selectively tune responses only in tissues in which the endogenous agonist exerts its physiological effects, and have the potential forgreater receptor subtype selectivity. The GPCRs allosteric modulators have been found and some of them have been in clinical use. Under the strategy of allosterism on structure activity relationship and target directed screening, more and more GPCRs allosteric modulators will be developed in the future.