P-糖蛋白抑制剂研究进展  

Advances in P-glycoprotein inhibitor research

作　　者：曾怡馨 蒋建东 孔维佳[1] ZENG Yi-xin;JIANG Jian-dong;KONG Wei-jia(Virus Unit of Institute of Pharmaceutical Biotechnology,Institute of Materia Medica,Chinese Academy of Medical Sciences,Peking Union Medical College,Beijing 100050,China;State Key Laboratory of Bioactive Natural Products and Function of Natural Medines,Institute of Materia Medica,Chinese Academy of Medical Sciences,Peking Union Medical College,Beijing 100050,China)

机构地区：[1]中国医学科学院北京协和医学院医药生物技术研究所病毒室,北京100050 [2]中国医学科学院北京协和医学院药物研究所天然药物活性物质与功能国家重点实验室,北京100050

出　　处：《中国药理学通报》2024年第12期2201-2206,共6页Chinese Pharmacological Bulletin

基　　金：中国医学科学院医学与健康科技创新工程项目(No 2021-I2M-1-009,2022-I2M-2-002)。

摘　　要：P-糖蛋白(P-glycoprotein,P-gp)过表达是包括抗肿瘤药物在内多种药物治疗耐药的主要原因之一。P-gp的底物十分广泛,能够通过扭曲-挤压机制将药物排出细胞,导致耐药。为解决P-gp介导的多药耐药问题,有多种抑制剂正在被研究。该文综述了目前能够抑制P-gp的小分子化合物、天然来源化合物和药物辅料,并总结了目前P-gp抑制剂的作用机制,主要有竞争性或非竞争性抑制、刺激ATP酶活性、下调表达量和变构调节。目前主要是药物相互作用和毒性反应限制了其临床应用。Overexpression of P-glycoprotein(P-gp)is one of the major causes of therapeutic resistance to a variety of drugs,including antitumor drugs.P-gp has a wide range of substrates that are capable of expelling drugs from the cell via a twist-squeeze mechanism,leading to drug resistance.To address the problem of P-gp-mediated multidrug resistance,several inhibitors are being investigated.This article reviews the current small molecule compounds,natural source compounds and pharmaceutical excipients capable of inhibiting P-gp,and summarizes the current mechanisms of action of P-gp inhibitors,which are mainly competitive or non-competitive inhibition,stimulation of ATPase activity,down-regulation of expression,and metamorphic modulation.Currently,it is mainly the drug interactions and toxic reactions that limit their clinical applications.

关 键 词：P-糖蛋白 ATP结合盒转运体 多药耐药 药物相互作用 天然产物 辅料 

分 类 号：R96[医药卫生—药理学]