蛋白降解靶向嵌合体的研究进展  

Research progress in proteolysis-targeting chimeras

作　　者：王美军 杨翠慧 张美慧[1] 董金华[1] WANG Mei-jun;YANG Cui-hui;ZHANG Mei-hui;DONG Jin-hua(Key Laboratory of Structure-Based Drugs Design and Discovery(Shenyang Pharmaceutical University),Ministry of Education,Shenyang 110016,China)

机构地区：[1]沈阳药科大学、基于靶点的药物设计与研究教育部重点实验室,辽宁沈阳110016

出　　处：《中国药物化学杂志》2023年第4期303-314,共12页Chinese Journal of Medicinal Chemistry

摘　　要：蛋白降解靶向嵌合体(PROTAC)是一种依赖泛素-蛋白酶体系统(UPS)降解与目标疾病相关蛋白质的异质双功能小分子。近期针对传统雌激素受体和雄激素受体的PROTAC药物已进入临床试验阶段,使得PROTAC得到更加广泛的关注。本文介绍了PROTAC的发展历程以及研究现状,总结了PROTAC分子靶向不可成药蛋白、克服药物靶标积累和耐药性等技术优势,并对如何寻找最佳的蛋白质降解靶点、寻找新的E3连接酶、扩大临床治疗范围等发展趋势进行综述。Proteolysis-targeting chimera(PROTAC)is a heterogeneous bifunctional small molecule that relies on the ubiquitin-proteasome system(UPS)to degrade proteins related to target diseases.Recently,some PROTAC drugs targeting traditional estrogen receptors and androgen receptors entered the clinical trial stage,making PROTACs more widely concerned.This paper introduces the development history and research progress of PROTAC,summarizes the technical advantages of PROTAC molecule,such as targeting non-available proteins,overcoming the accumulation of drug targets and drug resistance.The respect of PROTAC development trends of finding the best protein degradation targets,searching for new E3 ligases,and expanding the scope of clinical treatment,is also provide.

关 键 词：靶向蛋白质降解 蛋白降解靶向嵌合体 E3连接酶 发展趋势 

分 类 号：R914[医药卫生—药物化学]