双肾上腺皮质激素样激酶1小分子抑制剂的研究进展  

Research progress of small molecule inhibitors of doublecortin-like kinase 1

作　　者：陈玉平 李柯良 盛春泉 武善超 CHEN Yu-ping;LI Ke-liang;SHENG Chun-quan;WU Shan-chao(The Second Military Medical University,Shanghai 200433,China)

机构地区：[1]中国人民解放军海军军医大学,上海200433

出　　处：《药学学报》2022年第10期2914-2920,共7页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(22077138,81725020);上海市青年科技启明星计划(22QA1411300)。

摘　　要：双肾上腺皮质激素样激酶1(DCLK1)的过表达与多种恶性肿瘤的发生发展密切相关,抑制DCLK1活性,可以有效发挥抗肿瘤作用,已经成为抗肿瘤药物研发的热门领域。目前已有多个DCLK1小分子抑制剂表现出优秀的体内外抗肿瘤活性,有望为肿瘤治疗提供全新策略。基于此,本文综述了DCLK1小分子抑制剂的发现、结构类型、结构优化、生物活性及作用机制等方面的研究进展,以期为开发基于DCLK1的新型抗肿瘤小分子抑制剂提供借鉴和参考。The overexpression of doublecortin-like kinase 1(DCLK1)is closely related to the occurrence and development of various malignant tumors.Discovery of novel anti-tumor agents targeting DCLK1 represents a hot spot in this field.So far,several DCLK1 small molecule inhibitors with excellent anti-tumor activity in vitro and in vivo have been designed and synthesized,which is expected to provide a new strategy for tumor therapy.This article reviews the research progress in the discovery,structure type,structural optimization,biological activity and mechanism of action of DCLK1 small molecule inhibitors,and provides research basis for the development of new anti-tumor small molecule inhibitors targeting DCLK1.

关 键 词：蛋白激酶 双肾上腺皮质激素样激酶1 抗肿瘤活性 小分子抑制剂 先导化合物 

分 类 号：R914[医药卫生—药物化学]