Dong Chao, Wang Yong, Tu Zhenlin, Yan Jingxue, Jiang Yiqing, Lu Tao, Chen Yadong, Liu Haichun
School of Science, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, 211198, PR China.
State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, PR China.
Future Med Chem. 2022 Dec;14(23):1811-1830. doi: 10.4155/fmc-2022-0252. Epub 2022 Dec 9.
ATM, a member of the PIKK-like protein family, plays a central role in responding to DNA double-strand breaks and other lesions to protect the genome against DNA damage. Loss of ATM's kinase function has been shown to increase the sensitivity of most cells to ionizing radiation. Therefore, ATM is thought to be a promising target for chemotherapy as a radiotherapy sensitizer. The mechanism of ATM in cancer treatment and the development of its inhibitors have become research hotspots. Here we present an overview of research concerning ATM protein domains, functions and inhibitors, as well as perspectives and insights for future development of ATM-targeting agents.
ATM是类PIKK蛋白家族的成员之一,在应对DNA双链断裂和其他损伤以保护基因组免受DNA损伤方面发挥着核心作用。研究表明,ATM激酶功能的丧失会增加大多数细胞对电离辐射的敏感性。因此,ATM被认为是一种有前景的化疗放疗增敏靶点。ATM在癌症治疗中的作用机制及其抑制剂的研发已成为研究热点。在此,我们对有关ATM蛋白结构域、功能和抑制剂的研究进行综述,并对ATM靶向药物的未来发展提出展望与见解。