靶向E3泛素连接酶的药物研究进展  

Progress of drugs targeting E3 ubiquitin ligase

作　　者：商廿颍 赵春阳 彭英[1] SHANG Nian-ying;ZHAO Chun-yang;PENG ying(Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China;Center for Drug Evaluation,National Medical Product Administration,Beijing 100022,China)

机构地区：[1]中国医学科学院北京协和医学院药物研究所,北京100050 [2]国家药品监督管理局药品审评中心,北京100022

出　　处：《中国药理学通报》2021年第6期749-755,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 82073835,81872855)。

摘　　要：泛素-蛋白酶体系统是真核细胞蛋白质降解的重要途径之一,在细胞的增殖、分化、凋亡以及DNA的修复等生理活动的调节中起着重要作用。E3泛素连接酶是泛素-蛋白酶体系统的重要组成部分,决定底物识别的特异性。E3泛素连接酶的失调会引起癌症、阿尔茨海默症和帕金森病等多种疾病。本文对靶向E3泛素连接酶的药物在癌症、阿尔茨海默病、帕金森病、糖尿病并发症、动脉粥样硬化以及炎症性肠炎等领域的研究进展进行了总结。目前能够开发成为药物的靶向E3泛素连接酶的小分子抑制剂或激动剂数量不多,我国在天然产物的研究与开发方面具有突出的优势,很多天然产物都具有靶向E3泛素连接酶的活性,值得进一步开发应用。The ubiquitin-proteasome pathway is one of the mostimportant pathways of cell protein degradation in eukaryotes,andplays an important role in the regulation of cell proliferation,dif-ferentiation,apoptosis,DNA repair and other physiological activi-ties.E3 ubiquitin ligase is the major component of ubiquitin-proteasome system,which is responsible for substrate recogni-tion.The abnormal regulation of E3 ubiquitin ligase may causemany diseases such as cancer,Alzheimer's disease and Parkin-son's disease.Here,we summarizes the progress of drugs targe-ting E3 ubiquitin ligase in cancer,Alzheimer's disease,Parkin-son's disease,diabetic complications,atherosclerosis,and inflam-matory bowel diseases.At present,only a few of small moleculeantagonists or agonists targeting E3 ubiquitin ligase are underdevelopment.The study of natural products in China is leadingthe way in the world,and numerous natural products have been i-dentified for pharmacological effects on E3ubiquitin ligase,which may open up a new avenue for multiple complex diseases.

关 键 词：E3泛素连接酶 酶抑制剂 酶激动剂 靶蛋白水解嵌合体 阿尔茨海默病 帕金森病 炎症性肠炎 

分 类 号：R-05[医药卫生] R341.31