靶向Ras蛋白类抗癌药物研究进展  

Recent advances in anticancer agent targeting Ras proteins

作　　者：张源 徐文清[1] ZHANG Yuan;XU Wen-qing(Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine,Institute of Radiation Medicine,Chinese Academy of Medical Sciences,Peking Union.Medical College,Tianjin 300192,China)

机构地区：[1]中国医学科学院放射医学研究所,天津市放射医学与分子核医学重点实验室,天津300192

出　　处：《中国新药杂志》2020年第9期1012-1017,共6页Chinese Journal of New Drugs

基　　金：中国医学科学院医学与健康创新工程(CIFMS,2017-I2M-3-019);天津市前沿技术与发展计划重点项目(14JCZDJC36400)。

摘　　要：大概1/3的人类癌症存在Ras原癌基因的突变,而Ras蛋白对于细胞的增殖分化等生理过程有着至关重要的作用,这使得Ras蛋白成为众人争相研究的对象。经过30多年的研究,发现Ras蛋白由于缺乏合适的药物分子结合口袋,难以成为有效的药物靶点蛋白,甚至认为"无药可成"。然而,近几年来结构生物学和生物信息学的不断发展,越来越多的证据表明Ras蛋白可以成为药物分子作用的靶点蛋白。本文综述了近几年来以Ras蛋白为靶点的抗癌药物研究进展,旨在为同类研究提供参考。Mutations in the Ras oncogene occur in about one-third of human cancers,and Ras proteins play a crucial role in many physiological processes,such as cell proliferation and differentiation,making Ras proteins a subject of intense researches.After more than 30 years of research,it is found that Ras proteins are difficult to develop as an effective drug target due to lacking of a suitable binding pocket,and even considered"undruggable".However,in recent years,with the development of structural biology and bioinformatics,there is increasing evidence proving that Ras proteins could be a kind of target protein for small molecules.In this paper,the research progress of anticancer agents targeting Ras proteins in recent years is reviewed aiming to provide corresponding references for similar researches.

关 键 词：Ras原癌基因 RAS蛋白 H-RAS K-RAS 抑制剂 抗癌药物 

分 类 号：R972.6[医药卫生—药品]