Abstract：
The deployment of DNA damage response (DDR) combats various forms of DNA damage, ensuring genomic stability. Cancer cells\' propensity for genomic instability offers therapeutic opportunities to selectively kill cancer cells by suppressing the DDR pathway. DNA-dependent protein kinase (DNA-PK), a nuclear serine/threonine kinase, is crucial for the non-homologous end joining (NHEJ) pathway in the repair of DNA double-strand breaks (DSBs). Therefore, targeting DNA-PK is a promising cancer treatment strategy. This review elaborates on the structures of DNA-PK and its related large protein, as well as the development process of DNA-PK inhibitors, and recent advancements in their clinical application. We emphasize our analysis of the development process and structure-activity relationships (SARs) of DNA-PK inhibitors based on different scaffolds. We hope this review will provide practical information for researchers seeking to develop novel DNA-PK inhibitors in the future.
摘要：
部署DNA损伤反应（DDR）对抗各种形式的DNA损伤，确保基因组稳定性。癌细胞对基因组不稳定性的倾向提供了通过抑制DDR途径选择性杀死癌细胞的治疗机会。DNA依赖性蛋白激酶（DNA-PK），核丝氨酸/苏氨酸激酶，对于DNA双链断裂（DSB）修复中的非同源末端连接（NHEJ）途径至关重要。因此,靶向DNA-PK是一种有前途的癌症治疗策略.本文综述了DNA-PK及其相关大蛋白的结构,以及DNA-PK抑制剂的发展过程，以及其临床应用的最新进展。我们强调我们对基于不同支架的DNA-PK抑制剂的开发过程和结构-活性关系（SARs）的分析。我们希望这篇综述将为未来寻求开发新的DNA-PK抑制剂的研究人员提供实用信息。
