靶向DNA-PK的抗肿瘤药物研发进展
Research progress of DNA-PK inhibitors in the cancer treatment
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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。Abstract: 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 phosphatidylinositol-3-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.
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