P-糖蛋白抑制剂及其构效关系研究进展

Research advance on P-glycoprotein inhibitors and the structure-activity relationship

P-糖蛋白(P-glycoprotein,P-gp)是一种ATP依赖性的跨膜转运蛋白,可将多种结构和药效不同的化合物排出细胞。P-gp具有重要的病理生理功能,既影响药物的体内过程,也是肿瘤产生多药耐药的主要原因之一。因此,开发P-gp的抑制剂对于药物代谢动力学行为的调节及逆转肿瘤多药耐药具有重要意义。本文总结了近年来P-gp抑制剂开发及构效关系(structure-activity relationship,SAR)的研究进展,这对进一步筛选及合成理想的P-gp抑制剂有重要的指导作用。

P-glycoprotein （P-gp） is an important ATP-dependent transmembrane transporter, which can pump out a large number of structural and functional diverse compounds. P-gp plays a prominent role in physiological and pathological functions. It is not only crucial to drug disposition, but also one of the main causes of multidrug resistance （MDR）. Therefore, developing P-gp inhibitors is significant to researches on modulation of drug pharmacokinetics and reversion of multidrug resistance. In this paper, we summarize studies on structure-activity relationship of P-gp inhibitors, which will give us important information for screening and synthesizing desirable P-gp inhibitors in the future.