蛋白降解靶向嵌合体在抗肿瘤治疗中的研究进展  

Progress of proteolytic-targeting chimera in anti-tumor treatment

作　　者：汪子肖 李永生 范婷 张玲[1] 杨红[1] 毕学苑 WANG Zi-xiao;LI Yong-sheng;FAN Ting;ZHANG Ling;YANG Hong;BI Xue-yuan(Honghui Hospital Affiliated to Xi-an Jiaotong University,Xi-an SHANNXI 710054,China)

机构地区：[1]西安交通大学附属红会医院,陕西西安710054

出　　处：《中国新药与临床杂志》2023年第7期428-435,共8页Chinese Journal of New Drugs and Clinical Remedies

基　　金：西安市青年人才托举计划(095920201315);西安市红会医院“高层次人才”项目(2021GCCRC09);医学科研发展基金项目(B21114FN,B21115FN)。

摘　　要：随着蛋白降解靶向嵌合体(PROTAC)的发展,利用蛋白质降解机制来降解致癌蛋白的治疗策略取得了突破性进展。PROTAC能通过多聚泛素化-蛋白酶体途径诱导致病蛋白降解,有望克服传统肿瘤抑制剂易脱靶或靶标突变带来的耐药性等问题。近年来,多款PROTAC小分子降解剂相继进入Ⅰ期或Ⅱ期临床试验,如何通过优化其分子结构及探索新靶点来开发更多临床有效的PROTAC小分子降解剂已成为新热点。With the development of proteolytic-targeting chimera(PROTAC),breakthrough progress have been made in therapeutic strategies of degrading carcinogenic proteins through protein degradation mechanism.PROTAC can induce the degradation of pathogenic proteins through the ubiquitin-proteasome system(UPS),which is expected to overcome the problems of drug resistance caused by the easy off-target or target mutation of traditional tumor inhibitors.In recent years,several PROTAC small molecule degradants have successively entered phase I or I clinical trials.How to develop more effective PROTAC small molecule degradants by optimizing molecular structures and exploring new targets has become a new hotspot.

关 键 词：蛋白降解靶向嵌合体 泛素蛋白连接酶类 分子结构 抗肿瘤活性 

分 类 号：R914[医药卫生—药物化学] R979.1[医药卫生—药学]