靶向CDK2的小分子抑制剂的研究进展  

Research Progress on Small Molecules Inhibitors Targeting CDK2

作　　者：冯晋 程建昕 FENG Jin;CHENG Jianxin(Jiangxi Provincial Key Laboratory of Drug Design and Evaluation,School of Pharmacy,Jiangxi Normal University of Science and Technology,330013,Nanchang,PRC)

机构地区：[1]江西科技师范大学药学院,江西省药物分子设计与评价重点实验室,南昌330013

出　　处：《江西科学》2025年第1期171-180,共10页Jiangxi Science

基　　金：国家自然科学基金项目(22063004)。

摘　　要：目的:目前已有多个细胞周期蛋白依赖性激酶2(CDK2)的小分子抑制剂在临床阶段表现出优异的体内外抗肿瘤活性,有望为肿瘤治疗提供全新策略。方法:通过检索国内外CDKS抑制剂的文献,对调控CDK2功能的信号通路及小分子药物的生物活性、结合模式等方面进行系统的综述。结果:CDK2抑制剂主要包括选择性抑制剂、ATP竞争性抑制剂和非ATP竞争性抑制剂,可结合CDK2不同位点发挥作用。意义:既往CDK2抑制剂是非特异性的,一直以来存在受脱靶效应限制的诸多问题。鉴于此,开发靶向CDK2的新型抗肿瘤小分子抑制剂具有一定的研究意义。Objective:At present,several small molecule inhibitors of cyclin-dependent kinase 2(CDK2)have shown excellent anti-tumor activity in vitro and in vivo at the clinical stage,which is expected to provide a new strategy for tumor treatment.Methods:By searching the literature of CDKS inhibitors at home and abroad,the signaling pathways regulating CDK2 function and the biological activity and binding mode of small molecule drugs were systematically reviewed.Results:CDK2 inhibitors mainly include selective inhibitors,ATP competitive inhibitors and non-ATP competitive inhibitors,which can act on different bind sites of CDK2.Significance:Previous CDK2 inhibitors are non-specific,and faced numerous challenges due to off-target effects.In light of this,the development of new anti-tumor small molecule inhibitors targeting CDK2 holds certain research significance.

关 键 词：细胞周期蛋白依赖性激酶2 小分子抑制剂 肿瘤 细胞周期 研究进展 

分 类 号：R914.2[医药卫生—药物化学]