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Adjusted degradation of BRD4 S and BRD4 L based on fine structural modifications of the pyrrolopyridone scaffold

文献类型：期刊论文

作者Chen, Jingjing5; He, Huixin2,3; Wei, Aihuan4; Li, Yalei3; Cheng, Gang1; Qin, Hui2,4; Zhong, Hanyue2,4; Liu, Hongchun3; Geng, Meiyu2,3,5; Shen, Aijun2,3
刊名EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
出版日期2022-06-05
卷号236页码:14
ISSN号0223-5234
关键词PROTAC Pyrrolopyridone BRD4 S Selectivity
DOI10.1016/j.ejmech.2022.114259
通讯作者Shen, Aijun(shenaj@simm.ac.cn) ; Hu, Youhong(yhhu@simm.ac.cn)
英文摘要Novel pyrrolopyridone BET degraders were designed and synthesized based on the binding mode between the pyrrolopyridone BET inhibitor with the BRD4 protein. The potent degraders on MV-4-11 cells were discovered through structure-activity relationship study. Modification of warhead on pyrrolopyridone BET degraders significantly regulates BRD4 isoform (long and short) protein degradation, which induces differential cell cycle arrest and apoptosis on MV-4-11 cells. Docking study revealed that the fine structural modification of BET degraders may bind with the BD domain of BRD4 protein to engage various surface areas that bind with CRBN.
WOS关键词BROMODOMAIN ; DISCOVERY ; POTENT
资助项目Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020357] ; National Natural Science Foundation of China[81703340] ; National Natural Science Foundation of China[82173831] ; Shanghai Pujiang Program[2019PJD056] ; Science and Technology Commission of Shanghai Municipality[18431907100] ; Science and Technology Commission of Shanghai Municipality[21ZR1475000]
WOS研究方向Pharmacology & Pharmacy
语种英语
出版者ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
WOS记录号WOS:000793420300001
源URL[http://119.78.100.183/handle/2S10ELR8/301065]  
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.Zhejiang Chinese Med Univ, Coll Pharmaceut Sci, 548 Binwen Rd, Hangzhou 310053, Peoples R China
2.Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 110039, 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.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, State Key Lab Drug Res, 555 ZuChongZhi Rd, Shanghai 201203, Peoples R China
5.UCAS, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, 1 Xiangshanzhi Rd, Hangzhou 310024, Peoples R China
推荐引用方式
GB/T 7714		 Chen, Jingjing,He, Huixin,Wei, Aihuan,et al. Adjusted degradation of BRD4 S and BRD4 L based on fine structural modifications of the pyrrolopyridone scaffold[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2022,236:14.
APA Chen, Jingjing.,He, Huixin.,Wei, Aihuan.,Li, Yalei.,Cheng, Gang.,...&Hu, Youhong.(2022).Adjusted degradation of BRD4 S and BRD4 L based on fine structural modifications of the pyrrolopyridone scaffold.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,236,14.
MLA Chen, Jingjing,et al."Adjusted degradation of BRD4 S and BRD4 L based on fine structural modifications of the pyrrolopyridone scaffold".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 236(2022):14.

入库方式： OAI收割

来源：上海药物研究所

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