Discovery of Potent Irreversible Pan-Fibroblast Growth Factor Receptor (FGFR) Inhibitors
文献类型:期刊论文
作者 | Wang, Yuming1,3; Li, Lijun2,3; Fan, Jun1,3; Dai, Yang2,3; Jiang, Alan2,3; Geng, Meiyu2,3![]() ![]() ![]() |
刊名 | JOURNAL OF MEDICINAL CHEMISTRY
![]() |
出版日期 | 2018-10-25 |
卷号 | 61期号:20页码:9085-9104 |
ISSN号 | 0022-2623 |
DOI | 10.1021/acs.jmedchem.7b01843 |
文献子类 | Article |
英文摘要 | Fibroblast growth factor receptors (FGFRI-4) are promising therapeutic targets in many cancers. With the resurgence of interest in irreversible inhibitors, efforts have been directed to the discovery of irreversible FGFR inhibitors. Currently, several selective irreversible inhibitors are being evaluated in clinical trials that could covalently target a conserved cysteine in the P-loop of FGFR In this article, we used a structure-guided approach that is rationalized by a computer-aided simulation to discover the novel and irreversible pan-FGFR inhibitor, 9g, which provided superior FGFR in vitro activities and decent selectivity over VEGFR2 (vascular endothelia growth factor receptor 2). In in vivo studies, 9g displayed clear antitumor activities in NCI-H1581 and SNU-16 xenograft mice models. Additionally, the diluting method confirmed the irreversible binding of 9g to FGFR. |
WOS关键词 | TYROSINE KINASE INHIBITORS ; SELECTIVE INHIBITOR ; CH5183284/DEBIO 1347 ; OVERCOME RESISTANCE ; COVALENT INHIBITORS ; BREAST-CANCER ; SOLID TUMORS ; DESIGN ; MODELS ; FAMILY |
资助项目 | National Natural Science Foundation[81573271] ; National Natural Science Foundation[81773762] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020303] ; Shanghai Science and Technology Commission[15431901300] |
WOS研究方向 | Pharmacology & Pharmacy |
语种 | 英语 |
WOS记录号 | WOS:000448754900007 |
出版者 | AMER CHEMICAL SOC |
源URL | [http://119.78.100.183/handle/2S10ELR8/279527] ![]() |
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 | Ai, Jing; Duan, Wenhu |
作者单位 | 1.Chinese Acad Sci, SIMM, Dept Med Chem, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, SIMM, State Key Lab Drug Res, Div Antitumor Pharmacol, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China; 3.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China |
推荐引用方式 GB/T 7714 | Wang, Yuming,Li, Lijun,Fan, Jun,et al. Discovery of Potent Irreversible Pan-Fibroblast Growth Factor Receptor (FGFR) Inhibitors[J]. JOURNAL OF MEDICINAL CHEMISTRY,2018,61(20):9085-9104. |
APA | Wang, Yuming.,Li, Lijun.,Fan, Jun.,Dai, Yang.,Jiang, Alan.,...&Duan, Wenhu.(2018).Discovery of Potent Irreversible Pan-Fibroblast Growth Factor Receptor (FGFR) Inhibitors.JOURNAL OF MEDICINAL CHEMISTRY,61(20),9085-9104. |
MLA | Wang, Yuming,et al."Discovery of Potent Irreversible Pan-Fibroblast Growth Factor Receptor (FGFR) Inhibitors".JOURNAL OF MEDICINAL CHEMISTRY 61.20(2018):9085-9104. |
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。