Enhancing the cellular anti-proliferation activity of pyridazinones as c-met inhibitors using docking analysis
文献类型：期刊论文
| 作者 | Xing, Weiqiang2; Ai, Jing3 ; Jin, Shiyu2; Shi, Zhangxing2; Peng, Xia3; Wang, Lang2; Ji, Yinchun3; Lu, Dong2; Liu, Yang2; Geng, Meiyu3
|
| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2015-05-05 |
| 卷号 | 95页码:302-312 |
| 关键词 | Pyridazinone c-Met inhibitor Anticancer Docking study |
| ISSN号 | 0223-5234 |
| DOI | 10.1016/j.ejmech.2015.03.041 |
| 文献子类 | Article |
| 英文摘要 | A series of 2, 6-disubstituted pyridazinone derivatives were evaluated and optimized for their c-Met inhibitory activity in enzyme and cellular assay. An analysis of the SAR results arising from computer modeling analysis of members of the library led to the proposal that in order to obtain optimal inhibitory activity in cellular systems the lipophilic/hydrophilic properties of individual structural fragments in the inhibitors need to match those of corresponding binding pockets in the enzyme. Guided by this proposal, the quinoline-pyridazinone 8a, containing hydrophobic 6-indolyl pyridazinone and quinoline moieties along with a hydrophilic morpholine terminal group, was designed and synthesized. The results of studies with this substance showed that it is a selective c-Met inhibitor with both a high enzyme inhibition IC50 value of 4.2 nM and a high EBC-1 cell proliferation inhibition 1050 value of 17 nM. (C) 2015 Elsevier Masson SAS. All rights reserved. |
| WOS关键词 | SELECTIVE KINASE INHIBITORS ; GROWTH-FACTOR RECEPTOR ; STRUCTURE-BASED DESIGN ; TARGET RESIDENCE TIME ; BIOLOGICAL EVALUATION ; DISCOVERY ; CANCER ; POTENT ; IDENTIFICATION ; OPTIMIZATION |
| 资助项目 | National Natural Science Foundation of China[81202392] ; National Natural Science Foundation of China[81225022] ; National Natural Science Foundation of China[81102461] ; National S&T Major Projects[2012ZX09301001-007] ; SA-SIBS Scholarship Program[00000000] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000354139900026 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276537]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药物化学研究室 |
| 通讯作者 | Hu, Youhong |
| 作者单位 | 1.Zhejiang Univ, Coll Pharmaceut Sci, Zhejiang Prov Key Lab Anticanc Drug Res, ZJU ENS Joint Lab Med Chem, Hangzhou 310058, Zhejiang, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Xing, Weiqiang,Ai, Jing,Jin, Shiyu,et al. Enhancing the cellular anti-proliferation activity of pyridazinones as c-met inhibitors using docking analysis[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2015,95:302-312. |
| APA | Xing, Weiqiang.,Ai, Jing.,Jin, Shiyu.,Shi, Zhangxing.,Peng, Xia.,...&Hu, Youhong.(2015).Enhancing the cellular anti-proliferation activity of pyridazinones as c-met inhibitors using docking analysis.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,95,302-312. |
| MLA | Xing, Weiqiang,et al."Enhancing the cellular anti-proliferation activity of pyridazinones as c-met inhibitors using docking analysis".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 95(2015):302-312. |
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。