靶向DNA-PK的抗肿瘤药物研发进展

Research progress of DNA-PK inhibitors in the cancer treatment

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.