题名 | Synthesis, biological evaluation, QSAR and molecular dynamics simulation studies of potential fibroblast growth factor receptor 1 inhibitors for the treatment of gastric cancer |
作者 | |
发表日期 | 2017-02-15 |
发表期刊 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 影响因子和分区 |
语种 | 英语 |
原始文献类型 | Article |
关键词 | Design Fibroblast growth factor receptor 1 Gastric cancer Quantitative structure-activity relationship |
其他关键词 | GENE AMPLIFICATION ; DISCOVERY ; MODE ; FGFR ; OPTIMIZATION ; APATINIB ; THERAPY ; PACKAGE ; AMBER |
摘要 | Accumulating evidence suggests that fibroblast growth factor receptor 1 (FGFR1) is an attractive target in gastric cancer therapy. Based on our previous discovery of two non-ATP competitive FGFR1 inhibitors, A114 and A117, we designed and screened a series of compounds with the framework of bisaryl-1,4-dien-3-one. Among them, D12 and D15 exhibited the most potent FGFR1 inhibitory activity, which was ATP-independent. Furthermore, a quantitative structure-activity relationship analysis of 41 analogs demonstrated that the specific structural substitutions alter their bioactivities. Molecular docking and dynamics simulation analysis indicated the hydrophobic interaction at the FGFR1-D12/D15 interaction was dominant. Evaluation for anti-gastric cancer efficacy of D12 and D15 indicated effective inhibition of cell proliferation, apoptosis induction and cell cycle arrest. Thus, these two FGFR1 inhibitors have therapeutic potential in the treatment of gastric cancer, and this study provides will contribute to the rational design of novel non-ATP competitive FGFR1 inhibitors. (C) 2016 Elsevier Masson SAS. All rights reserved. |
资助项目 | National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81402839, 81272462, 81473242]; Natural Science Foundation of Zhejiang Province of ChinaNatural Science Foundation of Zhejiang Province [LY17H160059]; Technology Foundation for Medical Science of Zhejiang Province [2012KYA129] |
出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
出版地 | ISSY-LES-MOULINEAUX |
ISSN | 0223-5234 |
EISSN | 1768-3254 |
卷号 | 127页码:885-899 |
DOI | 10.1016/j.ejmech.2016.10.066 |
页数 | 15 |
WOS类目 | Chemistry, Medicinal |
WOS研究方向 | Pharmacology & Pharmacy |
WOS记录号 | WOS:000397172800070 |
收录类别 | SCIE ; PUBMED ; SCOPUS ; IC |
URL | 查看原文 |
Pubmed记录号 | 27829519 |
Scopus记录号 | 2-s2.0-85008191221 |
自科自定义期刊分类 | T3(B)类 |
通讯作者地址 | [Wu, Jianzhang]Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical Universtiy,Wenzhou,325035,China |
scopus学科分类 | Pharmacology;Drug Discovery;Organic Chemistry |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | https://kms.wmu.edu.cn/handle/3ETUA0LF/4271 |
专题 | 药学院(分析测试中心) 附属第一医院 第一临床医学院(信息与工程学院)、附属第一医院_计算机与信息管理系 第一临床医学院(信息与工程学院)、附属第一医院_内科学_消化内科 |
通讯作者 | Wu, Jianzhang |
作者单位 | 1.Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical Universtiy,Wenzhou,325035,China; 2.Department of Digestive Diseases,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,323000,China; 3.College of Chemistry and Materials Engineering,Wenzhou University,Wenzhou,325035,China; 4.College of Information Science and Computer Engineering,Wenzhou Medical University,Wenzhou,325035,China |
第一作者单位 | 药学院(分析测试中心); 生物有机与药物化学研究中心 |
通讯作者单位 | 药学院(分析测试中心); 生物有机与药物化学研究中心 |
第一作者的第一单位 | 药学院(分析测试中心) |
推荐引用方式 GB/T 7714 | Ying, Shilong,Du, Xiaojing,Fu, Weitao,et al. Synthesis, biological evaluation, QSAR and molecular dynamics simulation studies of potential fibroblast growth factor receptor 1 inhibitors for the treatment of gastric cancer[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2017,127:885-899. |
APA | Ying, Shilong., Du, Xiaojing., Fu, Weitao., Yun, Di., Chen, Liping., ... & Liang, Guang. (2017). Synthesis, biological evaluation, QSAR and molecular dynamics simulation studies of potential fibroblast growth factor receptor 1 inhibitors for the treatment of gastric cancer. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 127, 885-899. |
MLA | Ying, Shilong,et al."Synthesis, biological evaluation, QSAR and molecular dynamics simulation studies of potential fibroblast growth factor receptor 1 inhibitors for the treatment of gastric cancer".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 127(2017):885-899. |
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