机构：[1]Department of Respiratory and Critical Care Medicine and Targeted Tracer Research and Development Laboratory and Institute of Respiratory Health and State Key Laboratory of Respiratory Health and Multimorbidity and Laboratory of Neuro-system and Multimorbidity, West China Hospital, Sichuan University, Chengdu 610041, Sichuan China.四川大学华西医院[2]Department of Dermatology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan China.四川大学华西医院[3]Frontiers Medical Center, Tianfu Jincheng Laboratory, Chengdu 610212, Sichuan China.
The protein kinase ataxia telangiectasia mutated (ATM) is a constituent of the phosphatidylinositol 3-kinase-related kinase (PIKK) family, exerting a pivotal influence on diverse cellular processes, notably the signaling of double-strand DNA breaks (DSB) and stress response. The dysregulation of ATM is implicated in the pathogenesis of cancer and other diseases such as neurodegeneration. Hence, ATM is deemed a promising candidate for potential therapeutic interventions across a spectrum of diseases. Presently, while ATM small molecule inhibitors are not commercially available, various selective inhibitors have progressed to the clinical research phase. Specifically, AZD1390, WSD0628, SYH2051, and ZN-B-2262 are under investigation in clinical studies pertaining to glioblastoma multiforme and advanced solid tumors, respectively. In this Perspective, we encapsulate the structure, biological functions, and disease relevance of ATM. Subsequently, we concentrate on the design concepts and structure-activity relationships (SAR) of ATM inhibitors, delineating potential avenues for the development of more efficacious ATM-targeted inhibitors.
基金：
This work was supported by the National Natural Science
Foundation of China (82073318) and the Support Program of
Science &Technology Department of Sichuan Provincial
(2023NSFSC1013)
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2024]版：
无
最新[2023]版：
大类|1 区医学
小类|1 区药物化学
第一作者：
第一作者机构：[1]Department of Respiratory and Critical Care Medicine and Targeted Tracer Research and Development Laboratory and Institute of Respiratory Health and State Key Laboratory of Respiratory Health and Multimorbidity and Laboratory of Neuro-system and Multimorbidity, West China Hospital, Sichuan University, Chengdu 610041, Sichuan China.
共同第一作者：
通讯作者：
通讯机构：[1]Department of Respiratory and Critical Care Medicine and Targeted Tracer Research and Development Laboratory and Institute of Respiratory Health and State Key Laboratory of Respiratory Health and Multimorbidity and Laboratory of Neuro-system and Multimorbidity, West China Hospital, Sichuan University, Chengdu 610041, Sichuan China.[3]Frontiers Medical Center, Tianfu Jincheng Laboratory, Chengdu 610212, Sichuan China.
推荐引用方式(GB/T 7714)：
Qian Chunlin,Li Xiaoxue,Zhang Jifa,et al.Small Molecular Inhibitors That Target ATM for Drug Discovery: Current Research and Potential Prospective[J].Journal Of Medicinal Chemistry.2024,doi:10.1021/acs.jmedchem.4c01064.
APA：
Qian Chunlin,Li Xiaoxue,Zhang Jifa&Wang Yuxi.(2024).Small Molecular Inhibitors That Target ATM for Drug Discovery: Current Research and Potential Prospective.Journal Of Medicinal Chemistry,,
MLA：
Qian Chunlin,et al."Small Molecular Inhibitors That Target ATM for Drug Discovery: Current Research and Potential Prospective".Journal Of Medicinal Chemistry .(2024)
医学