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Covalent docking modelling-based discovery of tripeptidyl epoxyketone proteasome inhibitors composed of aliphatic-heterocycles

文献类型：期刊论文

作者Dong, Xiao-Wu1; Zhang, Jian-Kang1,4; Xu, Lei2,3; Che, Jin-Xin1; Cheng, Gang5; Hu, Xiao-Bei2,3; Sheng, Li2,3; Gao, An-Hui2,3; Li, Jia2,3; Liu, Tao1,2
刊名EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
出版日期2019-02-15
卷号164页码:602-614
关键词Proteasome inhibitors Tripeptide Covalent docking Interaction mode
ISSN号0223-5234
DOI10.1016/j.ejmech.2018.12.064
通讯作者Liu, Tao(lt601@zju.edu.cn) ; Hu, Yong-Zhou(huyz@zju.edu.cn) ; Zhou, Yu-Bo(ybzhou@simm.ac.cn)
英文摘要The potential of specific proteasome inhibitors to act as anti-cancer agents has attracted intensive investigations. The proteasome can be covalently inhibited by epoxyketone derivatives via a two-step reaction. Several computational approaches have been developed to mimic the covalent binding event. Compound 1 composed of a six-membered heterocyclic ring was designed by using covalent docking. With a possible different binding mode from the clinical compound Carfilzomib, it occupied the 55 pocket of 20S proteasome and showed favorable inhibitory activity. Subsequently optimization and evaluation were taken place. Among these compounds, 11h demonstrated extraordinary in vitro inhibitory activity and selectivity, and good in vivo proteasome inhibitory activity, a favorable pharmacokinetic profile and xenograft tumor inhibition. The possible binding pattern of compound 11h against proteasome was further fully explored via calculations, providing a theoretical basis for finding potent proteasome inhibitors. (C) 2018 Elsevier Masson SAS. All rights reserved.
WOS关键词BIOLOGICAL EVALUATION ; MOLECULAR DOCKING ; 20S PROTEASOME ; DESIGN ; DERIVATIVES ; IDENTIFICATION ; DEGRADATION ; GENERATION ; APOPTOSIS ; MYELOMA
资助项目National Natural Science Foundation of China ; Key Project of Zhejiang Provincial Natural Science Foundation of China ; Science and Technology Commission of Shanghai Municipality ; Strategic Priority Research Program of the Chinese Academy of Sciences ; National Major Scientific and Technological Special Project for Significant New Drugs Development
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000458221400039
出版者ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
源URL[http://119.78.100.183/handle/2S10ELR8/290564]  
专题新药研究国家重点实验室
通讯作者Liu, Tao; Hu, Yong-Zhou; Zhou, Yu-Bo
作者单位1.Zhejiang Univ, ZJU ENS Joint Lab Med Chem, Zhejiang Prov Key Lab Anticanc Drug Res, Hangzhou Inst Innovat Med,Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China
3.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
4.Zhejiang Univ City Coll, Sch Med, Hangzhou 310015, Zhejiang, Peoples R China
5.Zhejiang Chinese Med Univ, Coll Pharmaceut Sci, Hangzhou 311402, Zhejiang, Peoples R China
推荐引用方式
GB/T 7714		 Dong, Xiao-Wu,Zhang, Jian-Kang,Xu, Lei,et al. Covalent docking modelling-based discovery of tripeptidyl epoxyketone proteasome inhibitors composed of aliphatic-heterocycles[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2019,164:602-614.
APA Dong, Xiao-Wu.,Zhang, Jian-Kang.,Xu, Lei.,Che, Jin-Xin.,Cheng, Gang.,...&Zhou, Yu-Bo.(2019).Covalent docking modelling-based discovery of tripeptidyl epoxyketone proteasome inhibitors composed of aliphatic-heterocycles.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,164,602-614.
MLA Dong, Xiao-Wu,et al."Covalent docking modelling-based discovery of tripeptidyl epoxyketone proteasome inhibitors composed of aliphatic-heterocycles".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 164(2019):602-614.

入库方式： OAI收割

来源：上海药物研究所

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