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Discovery of selective HDAC/BRD4 dual inhibitors as epigenetic probes

文献类型：期刊论文

作者Chen, Jingjing1,2; Li, Yalei3; Zhang, Jie1,2; Zhang, Minmin3; Wei, Aihuan2; Liu, Hongchun3; Xie, Zhicheng1,2; Ren, Wenming2; Duan, Wenwen2; Zhang, Zhuo1,2
刊名EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
出版日期2021
卷号209页码:20
关键词HDAC BRD4 Selective dual inhibitors Anticancer
ISSN号0223-5234
DOI10.1016/j.ejmech.2020.112868
通讯作者Shen, Aijun(shenaj@simm.ac.cn) ; Hu, Youhong(yhhu@simm.ac.cn)
英文摘要According to the binding mode of ABBV-744 with bromodomains and the cape space of HDAC, the novel selective HDAC/BRD4 dual inhibitors were designed and synthesized by the pharmacophore fusion strategy. Evaluating the biomolecular activities through SARs exploration identified three kinds of selective dual inhibitors 41c (HDAC1/BRD4), 43a (pan-HDAC/BRD4) and 43d (HDAC6/BRD4(BD2)), whose target-related cellular activities in MV-4-11 cells were also confirmed. Significantly, the selective dual inhibitor 41c (HDAC1/BRD4) exhibited synergistic effects against MV-4-11 cells, which strongly induced G0/G1 cell cycle arrest and apoptosis, and the first HDAC6/BRD4(BD2) dual inhibitor was found. This study provides support for selective HDAC/BRD4 dual inhibitors as epigenetic probes based on pyrrolopyridone core for the future biological evaluation in different cancer cell lines. (c) 2020 Elsevier Masson SAS. All rights reserved.
WOS关键词HISTONE DEACETYLASE ; BET ; EXPRESSION ; APOPTOSIS ; PROTEINS ; CANCER ; DESIGN
资助项目Personalized MedicinesddMolecular Signature-based Drug Discovery and Development, Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020357] ; National Natural Science Foundation of China[81703340]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000600418500015
出版者ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
源URL[http://119.78.100.183/handle/2S10ELR8/296287]  
专题新药研究国家重点实验室
通讯作者Shen, Aijun; Hu, Youhong
作者单位1.Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 110039, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, State Key Lab Drug Res, 555 ZuChongZhi Rd, Shanghai 201203, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
4.UCAS, Sch Pharmaceut Sci & Technol, Hangzhou Inst Adv Study, Hangzhou 310024, Peoples R China
推荐引用方式
GB/T 7714		 Chen, Jingjing,Li, Yalei,Zhang, Jie,et al. Discovery of selective HDAC/BRD4 dual inhibitors as epigenetic probes[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2021,209:20.
APA Chen, Jingjing.,Li, Yalei.,Zhang, Jie.,Zhang, Minmin.,Wei, Aihuan.,...&Hu, Youhong.(2021).Discovery of selective HDAC/BRD4 dual inhibitors as epigenetic probes.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,209,20.
MLA Chen, Jingjing,et al."Discovery of selective HDAC/BRD4 dual inhibitors as epigenetic probes".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 209(2021):20.

入库方式： OAI收割

来源：上海药物研究所

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