靶向DNA-PK的抗肿瘤药物研发进展  

Research progress of DNA-PK inhibitors in the cancer treatment

作　　者：蔡田 亢炳皓 程越 黄敏[1] 赵临襄[1] CAI Tian;KANG Bing-hao;CHENG Yue;HUANG Min;ZHAO Lin-xiang(Key Laboratory of Structure-Based Drug Design and Discovery,Ministry of Education,Shenyang Pharmaceutical University,Shenyang 110016,China)

机构地区：[1]沈阳药科大学,基于靶点的药物设计与研究教育部重点实验室,辽宁沈阳110016

出　　处：《药学学报》2023年第8期2218-2225,共8页Acta Pharmaceutica Sinica

基　　金：辽宁省“兴辽英才”项目(XLYC1902089);沈阳药科大学创新创业训练计划项目(202210163116).

摘　　要：DNA双链断裂(DNA double strand breaks,DSBs)是毒性最高的DNA损伤形式,其主要通过非同源末端连接(non-homologous end joining,NHEJ)进行修复。DNA依赖激酶(DNA-dependent protein kinase,DNA-PK)属于磷脂酰肌醇3激酶相关蛋白激酶家族(phosphatidylinositol-3-kinase-related protein kinase family,PIKK),是NHEJ修复通路的关键激酶之一。DNA-PK在多种癌症细胞中异常表达,并与恶性肿瘤的发生、发展和耐药密切相关。本文综述了具有抗肿瘤作用的代表性DNA-PK抑制剂,以期为新型DNA-PK抑制剂的抗肿瘤药物研发提供参考。The most toxic DNA damage is DNA double strand breaks(DSBs),which are mainly repaired by non-homologous end joining(NHEJ).DNA-dependent protein kinase(DNA-PK)belongs to phosphatidylinositol3-kinase-related protein kinase family(PIKK)and plays a key role in NHEJ.DNA-PK is overexpressed in a variety of cancer cells and is related to the occurrence,development and drug resistance of malignant tumors.In this article,the representative DNA-PK inhibitors with anticancer effects are reviewed,in order to provide a reference to discovery novel DNA-PK inhibitors.

关 键 词：DNA损伤 抗肿瘤 DNA依赖激酶 抑制剂 

分 类 号：R914[医药卫生—药物化学]