蛋白水解靶向嵌合分子的小分子抗肿瘤药物的研究进展  

Research progress on small-molecule protein proteolysis-targeting chimeras as antitumor agents

作　　者：崔洁[1] 魏会强[2] 宁洪鑫 李祎亮[2] CUI Jie;WEI Hui-qiang;NING Hong-Xin;LI Yi-liang(Tianjin University of Traditional Chinese Medicine,Tianjin 300193,China;Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine,Institute of Radiation Medicine,Chinese Academy of Medical Science&Peking Union Medical College,Tianjin 300192,China)

机构地区：[1]天津中医药大学,天津300193 [2]中国医学科学院北京协和医学院放射医学研究所,天津300192

出　　处：《现代药物与临床》2019年第10期3187-3191,共5页Drugs & Clinic

基　　金：中央高校基本科研业务费专项资金资助项目（3332018117）;中国医学科学院医学与健康科技创新工程项目（2016-I2M-3-022和2017-I2M-3-019）

摘　　要：近年来蛋白靶向降解(PROTAC)技术作为一种新的治疗手段在抗肿瘤药物领域中得到了广泛的研究。PROTAC是一种双功能的小分子化合物,可以将靶蛋白与E3泛素连接酶连接形成三元复合物,通过泛素–蛋白酶体系降解靶蛋白。雌激素(ER)、雄激素(AR)、间变性淋巴瘤激酶(ALK)、布鲁顿酪氨酸激酶(BTK)、溴结构域蛋白4(BRD4)和细胞周期蛋白依赖激酶8(CDK8)等多种蛋白已经被选为靶蛋白进行了研究。对PROTAC的小分子抗肿瘤药物的研究进展进行综述。In recent years, proteolysis targeting chimera(PROTAC), as a new therapeutic method, has been widely studied in the field of anti-cancer drugs. PROTAC is a bifunctional small molecule compound, which can connect target protein with E3 ubiquitin ligase to form ternary complex, and degrade target protein through ubiquitin-protease system. Estrogen(ER), androgen(AR), anaplastic lymphoma kinase(ALK), bromine domain protein 4(BRD4), and cyclin dependent kinase 8(CDK8) have been selected as target proteins for a large number of studies. Research progress on small molecule anti-cancer drugs of PROTAC is reviewed in this paper.

关 键 词：PROTAC 泛素–蛋白酶体系 蛋白靶向降解 

分 类 号：R914[医药卫生—药物化学]