共济失调毛细血管扩张基因突变和Rad3相关激酶抑制剂的研究进展  

Ataxic telangiectasia gene mutation and Rad3-associated kinase inhibitors

作　　者：刘亚玲 赵东 朱艳丽 侯云雷 王绍宁[3] LIU Yaling;ZHAO Dong;ZHU Yanli;HOU Yunlei;WANG Shaoning(Department of Pharmacy,Tonghua Medical and Health Vocational College,Tonghua 134000,China;Jiangsu HAI-CI Biological Pharmaceutical Co.Ltd.,Yangtze River Pharmaceutical Group,Taizhou 225300,China;School of Pharmaceutical Engineering,Shenyang Pharmaceutical University,Shenyang 110016,China)

机构地区：[1]通化医药健康职业学院药学系,吉林通化134000 [2]扬子江药业集团江苏海慈生物药业有限公司,江苏泰州225300 [3]沈阳药科大学制药工程学院,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2024年第12期1575-1590,共16页Journal of Shenyang Pharmaceutical University

基　　金：沈阳药科大学归国人员科研启动基金项目(GGJJ2021104);辽宁省教育厅项目(LJKZ0959)。

摘　　要：共济失调毛细血管扩张突变基因和Rad3相关蛋白激酶是DNA修复的关键激酶,对基因组稳定以及肿瘤的发生、发展和治疗都至关重要。抑制共济失调毛细血管扩张突变基因和Rad3相关蛋白激酶可触发细胞周期阻滞,从而抑制由共济失调毛细血管扩张突变基因和Rad3相关蛋白激酶介导的修复途径,高效杀死肿瘤细胞。因此开发共济失调毛细血管扩张突变基因和Rad3相关蛋白激酶抑制剂是治疗具有DNA修复缺陷癌症的热点之一。本文主要综述了共济失调毛细血管扩张突变基因和Rad3相关蛋白激酶与DNA突变所致癌症的关联,并重点介绍了小分子共济失调毛细血管扩张突变基因和Rad3相关蛋白激酶抑制剂的研究进展,为后续基于共济失调毛细血管扩张突变基因和Rad3相关蛋白激酶的抗肿瘤药物研究提供了有益指导。Ataxia telangiectasia mutated genes and RAD3-associated protein kinase(ATR)are key kinases for DNA repair.Both of them are critical for genome stabilization as well as for tumor initiation,development,and treatment.The inhibition of ATR can trigger cell cycle arrest,thereby inhibiting the ATR-mediated repair pathway and efficiently killing tumor cells.Therefore,the development of ATR inhibitors is one of the hot spots in the treatment of cancer with DNA repair defects.This article mainly reviews the relationship between ATR and cancer caused by DNA mutation,and focuses on ATR inhibitors,which provides useful guidance for the subsequent study of tumor inhibitors.

关 键 词：共济失调毛细血管扩张突变基因和Rad3相关蛋白激酶 抑制剂 癌症 合成致死 

分 类 号：R914[医药卫生—药物化学]