基于组蛋白去乙酰化酶设计的多靶点抗肿瘤药物研究进展  

Research progress on design of multi-target anticancer drugs based on histone deacetylases

作　　者：丁娇丽 张志鹏 刘婧[2] 周维新 金一[1] 谢赛赛 DING Jiao-li;ZHANG Zhi-peng;LIU Jing;ZHOU Wei-xin;JIN Yi;XIE Sai-sai(National Pharmaceutical Engineering Research Center for Solid Preparation in Chinese Herbal Medicine,Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,China;School of Pharmacy,Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,China)

机构地区：[1]江西中医药大学中药固体制剂制造技术国家工程研究中心,南昌330004 [2]江西中医药大学药学院,南昌330004

出　　处：《中国新药杂志》2021年第3期236-245,共10页Chinese Journal of New Drugs

基　　金：国家自然科学基金资助项目(21807052);江西省科技创新杰出青年人才培养计划(20192BCB23018);江西省自然科学基金资助项目(20192ACBL21034)。

摘　　要：肿瘤的发生是一个多因子、多步骤的复杂过程。多靶点抗肿瘤药物能同时作用于肿瘤发生的多个疾病通路,比单靶点抗肿瘤药物有更好的治疗效果。研究显示,组蛋白去乙酰化酶(histone deacetylase,HDACs)在多种肿瘤细胞中过度表达,是肿瘤发生的关键靶点,因此以抑制HDACs为基础设计兼顾作用于其他靶点的多靶点抗肿瘤药物,成为重要的研究方向。目前已有5个HDAC抑制剂被批准上市用于治疗皮肤T细胞淋巴瘤、多发性骨髓瘤和外周T细胞淋巴瘤,还有十几个HDAC抑制剂正处于不同的临床研究阶段用于治疗各种癌症。基于此,本文综述了近年来此类多靶点分子的设计和生物活性研究,以期为进一步研发此类多靶点药物提供参考。The occurrence of tumor is a complicated process involving many factors and steps. It has been well validated that multi-target anticancer drugs that can simultaneously interact with two or more targets may offer greater therapeutic benefits than single target anticancer drugs. Studies indicate that HDACs are overexpressed in different human tumor cell lines,and have been identified as key targets of tumorigenesis. Therefore,design of multi-target anticancer drugs that can simultaneously act on HDACs and other targets has become an important research direction. To date,five HDAC inhibitors have been approved for the treatment of cancers including cutaneous T-cell lymphoma,multiple myeloma and peripheral T-cell lymphoma. There are several HDAC inhibitors at various stages of clinical trials against different cancers. Based on this,this paper reviews the design and biological activity of multi-target anticancer drugs based on the structures of HDAC inhibitors in recent years,aiming to provide reference for the further development of such multi-target molecules.

关 键 词：组蛋白去乙酰化酶抑制剂 多靶点 抗肿瘤药物 激酶 协同作用 

分 类 号：R979.1[医药卫生—药品]