药学学报, 2022, 57(3): 593-604
引用本文:
袁滢惠, 段吉隆, 惠子*, 谢恬*, 叶向阳*. 靶向ATR激酶抑制剂治疗癌症的研究进展[J]. 药学学报, 2022, 57(3): 593-604.
YUAN Ying-hui, DUAN Ji-long, HUI Zi*, XIE Tian*, YE Xiang-yang*. Research progress of ATR kinase-targeted inhibitors in the cancer therapy[J]. Acta Pharmaceutica Sinica, 2022, 57(3): 593-604.

靶向ATR激酶抑制剂治疗癌症的研究进展
袁滢惠, 段吉隆, 惠子*, 谢恬*, 叶向阳*
杭州师范大学药学院, 浙江省榄香烯类抗癌中药重点实验室, 浙产中药材资源开发与应用浙江省工程实验室, 浙江省浙八味等浙产中药材综合利用开发2011协同创新中心, 浙江 杭州 311121
摘要:
癌症,又称恶性肿瘤,是仅次于心脏病的第二大疾病,其特征是基因组不稳定和易突变性。共济失调毛细血管扩张突变基因和Rad3相关蛋白(ATR)是磷脂酰肌醇3-激酶(PIKK)家族的成员之一,属于丝氨酸-苏氨酸激酶,是DNA损伤反应(DNA damaging response,简称DDR)和DNA修复通路的关键激酶之一。本文从药物化学的角度综述了靶向ATR激酶抑制剂的作用机制、应用分类、联合用药等方面的最新进展,并阐述开发ATR激酶抑制剂抗肿瘤药物的可能挑战和未来前景,以期为本领域的科学工作者提供便利,为临床应用研究提供一定的参考意见。
关键词:    癌症      ATR激酶      抑制剂      临床研究      联合用药     
Research progress of ATR kinase-targeted inhibitors in the cancer therapy
YUAN Ying-hui, DUAN Ji-long, HUI Zi*, XIE Tian*, YE Xiang-yang*
School of Pharmacy;Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines;Engineering Laboratory of Development and Application of Traditional Chinese Medicines;Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
Abstract:
Cancer, also known as malignant tumor, is the second largest disease after heart disease, which is characterized by genomic instability and mutagenicity. Ataxia telangiectasia and RAD3-related kinase (ATR) are members of phosphatidylinositol 3-kinase (PIKK) family, belonging to serine/threonine kinase, one of the key kinases in DNA damage response (DDR) and DNA repair pathway. This paper reviews the latest progress in the ATR inhibitor field including mechanism of action (MOA), therapeutic applications, and the combination therapy from the perspective of medicinal chemistry. It also discusses the possible challenges and future directions of developing ATR inhibitor antitumor drugs, which could provide the scientists in this field the convenience for access the information and application guidance for clinical studies.
Key words:    cancer    ATR kinase    inhibitor    clinical research    combinational medication   
收稿日期: 2021-10-21
DOI: 10.16438/j.0513-4870.2021-1522
基金项目: 国家自然科学基金资助项目(82073686,81730108,81973635);杭州市“115”引进国(境)外智力项目计划(20200215);杭州师范大学卓越人才计划科研启动基金资助项目(4125C5021920419);杭州师范大学校级教改项目;国家科技部外国专家项目(G20200217005)。
通讯作者: 叶向阳,Tel:86-571-28860236,E-mail:xyye@hznu.edu.cn;惠子,E-mail:huizi@hznu.edu.cn;谢恬,E-mail:xbs@hznu.edu.cn
Email: xyye@hznu.edu.cn;huizi@hznu.edu.cn;xbs@hznu.edu.cn
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