拓扑异构酶1及其喜树碱类抑制剂的临床研究进展  

Topoisomerase 1 and its camptothecin inhibitors in clinic:research advances

作　　者：郭晓鹏[1,2] 冯思良[2] 王金辉[3] 俞腾飞[1] 

机构地区：[1]内蒙古医科大学药学院,呼和浩特010059 [2]军事医学科学院毒物药物研究所,北京100850 [3]沈阳药科大学中药学院,沈阳110016

出　　处：《国际药学研究杂志》2013年第4期405-414,共10页Journal of International Pharmaceutical Research

基　　金：国家"重大新药创制"科技重大专项资助项目(2012ZX09301003-004)

摘　　要：DNA拓扑异构酶1(Top 1)是一种重要的核酶,在DNA复制、转录、重组、修复、染色质组装和染色体分离等细胞代谢过程中,控制和修饰DNA拓扑结构。而且,Top1在多种肿瘤细胞中均过度表达。Top 1作为抗肿瘤药物靶点的确认,促进了新型抗肿瘤药物的发展。目前,研究最多的Top 1抑制剂主要是喜树碱类,已有3个喜树碱类药物上市(拓扑替康、伊立替康和贝洛替康)。本文对Top 1结构和功能的最新研究结果及其喜树碱类抑制剂的近期临床研究进展进行综述。DNA topoisomerase 1（Top 1） is an essential human enzyme that controls and modifies the topological state of DNA in many cellular metabolic processes,such as replication,transcription,recombination,repair,chromatin assembly and chromosome segregation.Besides,Top 1 is overexpressed in human cancers.Identification of Top 1 as a viable target of anticancer drugs has led to the development of new anticancer agents.Up to now,three camptothecin derivatives,topotecan,irinotecan,and belotecan,have been approved for clinical treatment of cancers.This article provides a brief review on the structure and function of Top 1,and summarizes the research advances on the camptothecin inhibitors in clinic.

关 键 词：拓扑异构酶1 结构 功能 拓扑异构酶1抑制剂 喜树碱类 

分 类 号：R914.2[医药卫生—药物化学] R969[医药卫生—药学]