中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 药理学第一研究室
Identification of a new series of potent diphenol HSP90 inhibitors by fragment merging and structure-based optimization

文献类型：期刊论文

作者Ren, Jing2; Li, Jian3,4; Wang, Yueqin1; Chen, Wuyan4; Shen, Aijun1; Liu, Hongchun1; Chen, Danqi2; Cao, Danyan2; Li, Yanlian2; Zhang, Naixia2
刊名BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
出版日期2014-06-01
卷号24期号:11页码:2525-2529
关键词Heat shock protein HSP90 Fragment-based drug discovery Anticancer
ISSN号0960-894X
DOI10.1016/j.bmcl.2014.03.100
文献子类Article
英文摘要Heat shock protein 90 (HSP90) is a molecular chaperone to fold and maintain the proper conformation of many signaling proteins, especially some oncogenic proteins and mutated unstable proteins. Inhibition of HSP90 was recognized as an effective approach to simultaneously suppress several aberrant signaling pathways, and therefore it was considered as a novel target for cancer therapy. Here, by integrating several techniques including the fragment-based drug discovery method, fragment merging, computer aided inhibitor optimization, and structure-based drug design, we were able to identify a series of HSP90 inhibitors. Among them, inhibitors 13, 32, 36 and 40 can inhibit HSP90 with IC50 about 20-40 nM, which is at least 200-fold more potent than initial fragments in the protein binding assay. These new HSP90 inhibitors not only explore interactions with an under-studied subpocket, also offer new chemotypes for the development of novel HSP90 inhibitors as anticancer drugs. (C) 2014 Elsevier Ltd. All rights reserved.
WOS关键词SHOCK-PROTEIN 90 ; DRUG DISCOVERY ; CHAPERONE ; LIGAND ; HEAT-SHOCK-PROTEIN-90 ; DESIGN
资助项目'Interdisciplinary Cooperation Team' Program for Science and Technology Innovation of the Chinese Academy of Sciences[00000000] ; '100 Talents Project' of CAS[00000000] ; National Natural Science Foundation of China[81072580] ; National Natural Science Foundation of China[81273368] ; National Natural Science Foundation of China[21272246] ; National Science & Technology Major Project 'Key New Drug Creation and Manufacturing Program' of China[2014ZX09507-002]
WOS研究方向Pharmacology & Pharmacy ; Chemistry
语种英语
WOS记录号WOS:000335518300029
出版者PERGAMON-ELSEVIER SCIENCE LTD
源URL[http://119.78.100.183/handle/2S10ELR8/277060]  
专题药理学第一研究室
药物化学研究室
通讯作者Geng, Meiyu
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China;
2.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, Natl Key Lab New Drug, Shanghai 201203, Peoples R China;
3.Chinese Acad Sci, Shanghai Inst Appl Phys, Shanghai 201204, Peoples R China;
4.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Ren, Jing,Li, Jian,Wang, Yueqin,et al. Identification of a new series of potent diphenol HSP90 inhibitors by fragment merging and structure-based optimization[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2014,24(11):2525-2529.
APA Ren, Jing.,Li, Jian.,Wang, Yueqin.,Chen, Wuyan.,Shen, Aijun.,...&Shen, Jingkang.(2014).Identification of a new series of potent diphenol HSP90 inhibitors by fragment merging and structure-based optimization.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,24(11),2525-2529.
MLA Ren, Jing,et al."Identification of a new series of potent diphenol HSP90 inhibitors by fragment merging and structure-based optimization".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 24.11(2014):2525-2529.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。