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Design and development of a novel series of oral bivalent BET inhibitors with potent anticancer activities

文献类型：期刊论文

作者Luo, Menglan3,4; Wu, Qian1,2; Yang, Yueyue1,3; Sun, Lin1,2; Huan, Xiajuan1,2; Tian, Changqing1,2; Xiong, Bing1,3; Miao, Zehong1,2; Wang, Yingqing1,2; Chen, Danqi1,3
刊名EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
出版日期2022-09-05
卷号239页码:13
关键词BET inhibitor BRD4 Bivalent inhibitor Anticancer
ISSN号0223-5234
DOI10.1016/j.ejmech.2022.114519
通讯作者Wang, Yingqing(yqwang@simm.ac.cn) ; Chen, Danqi(dqchen@simm.ac.cn)
英文摘要Bromodomain and extraterminal domain (BET) subfamily members are intriguing targets for cancer treatment. Most of the reported BET inhibitors were monovalent inhibitors. Recently, some bivalent inhibitors were disclosed, which bound to two bromodomains simultaneously. They had good activities, however, most of them also showed unsatisfactory pharmacokinetic properties, which were caused by long chain linkers. Based on our previous work on monovalent BRD4 inhibitors, we designed and synthesized a series of novel bivalent inhibitors with short and hydrophilic linkers. These compounds exhibited better activities than the corresponding monovalent inhibitors and good pharmacokinetic properties. Compound 21 showed excellent in vitro activities. And it also demonstrated potent in vivo antitumor efficacy under oral administration and was well tolerated in in vivo tests.
WOS关键词BROMODOMAINS ; DISCOVERY
资助项目National Science & Technology Major Project Key New Drug Creation and Manufacturing Program of China[2018ZX09711002-011-018] ; Science and Technology Commission of Shanghai Municipality[19ZR1467900] ; Science and Technology Commission of Shanghai Municipality[20ZR1468100]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000833534600002
出版者ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
源URL[http://119.78.100.183/handle/2S10ELR8/301902]  
专题新药研究国家重点实验室
通讯作者Wang, Yingqing; Chen, Danqi
作者单位1.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
2.Chinese Acad Sci, Canc Res Ctr, Shanghai Inst Mat Med, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201203, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
4.Shanghai Univ, Coll Sci, Dept Chem, 99 Shangda Rd, Shanghai 200444, Peoples R China
推荐引用方式
GB/T 7714		 Luo, Menglan,Wu, Qian,Yang, Yueyue,et al. Design and development of a novel series of oral bivalent BET inhibitors with potent anticancer activities[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2022,239:13.
APA Luo, Menglan.,Wu, Qian.,Yang, Yueyue.,Sun, Lin.,Huan, Xiajuan.,...&Chen, Danqi.(2022).Design and development of a novel series of oral bivalent BET inhibitors with potent anticancer activities.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,239,13.
MLA Luo, Menglan,et al."Design and development of a novel series of oral bivalent BET inhibitors with potent anticancer activities".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 239(2022):13.

入库方式： OAI收割

来源：上海药物研究所

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