Combining pharmacophore, docking and substructure search approaches to identify and optimize novel B-Raf(V600E) inhibitors
文献类型：期刊论文
| 作者 | Xu, Zhijian ; Yan, Guirui; Wang, Gaihong; Li, Bo; Zhu, Jianming; Sun, Peng; Zhang, Xiaodong; Luo, Cheng; Wang, Heyao; Zhu, Weiliang
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| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
 |
| 出版日期 | 2012-09-01 |
| 卷号 | 22期号:17页码:5428-5437 |
| 关键词 | B-Raf(V600E) inhibitors Pharmacophore Docking Substructure search |
| ISSN号 | 0960-894X |
| DOI | 10.1016/j.bmcl.2012.07.039 |
| 文献子类 | Article |
| 英文摘要 | In this study for searching novel B-Raf(V600E) inhibitors, pharmacophore-based virtual screening identified 1 as a hit bearing 5-benzylidene-2-thioxodihydropyrimidine-4,6(1H,5H)-dione. Based on 1, scaffold hopping inspired by molecular docking discovered 5-(furan-2-ylmethylene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione as a new and better scaffold. Substructure search with the new scaffold identified 28 active compounds, among which 12 compounds (42.9%) showed IC50 less than 1 mu M. Especially, compound 3o, which is 10-fold more potent than the hit 1, is a potent inhibitor comparable to that of the marketed drug vemurafenib. (C) 2012 Elsevier Ltd. All rights reserved. |
| WOS关键词 | B-RAF ; BRAF ; RESISTANCE ; KINASE ; BRAF(V600E) ; MUTATIONS ; MECHANISM ; DISCOVERY ; MELANOMA ; PLX4032 |
| 资助项目 | Ministry of Science and Technology[2010DFB73280] ; Ministry of Science and Technology[2012CB910403] ; Shanghai Science and Technology Innovation Program[08431900800] ; Natural Science Foundation[20721003] ; Natural Science Foundation[20972174] |
| WOS研究方向 | Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000308046400016 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277948]  |
| 专题 | 药理学第三研究室 药物发现与设计中心 |
| 通讯作者 | Wang, Heyao |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xu, Zhijian,Yan, Guirui,Wang, Gaihong,et al. Combining pharmacophore, docking and substructure search approaches to identify and optimize novel B-Raf(V600E) inhibitors[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2012,22(17):5428-5437. |
| APA | Xu, Zhijian.,Yan, Guirui.,Wang, Gaihong.,Li, Bo.,Zhu, Jianming.,...&Zhu, Weiliang.(2012).Combining pharmacophore, docking and substructure search approaches to identify and optimize novel B-Raf(V600E) inhibitors.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,22(17),5428-5437. |
| MLA | Xu, Zhijian,et al."Combining pharmacophore, docking and substructure search approaches to identify and optimize novel B-Raf(V600E) inhibitors".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 22.17(2012):5428-5437. |
入库方式： OAI收割
来源：上海药物研究所
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