Design, synthesis, and antiproliferative activity assessment of non-ATP-competitive fibroblast growth factor receptor 1 inhibitors

doi:10.1134/S1070363216120355

科研成果详情

题名	Design, synthesis, and antiproliferative activity assessment of non-ATP-competitive fibroblast growth factor receptor 1 inhibitors
作者	Ying S.1; Wang, Jia 1; Xu C.1; Kang Y.1; Zhang X.1; Shi L.1; Fan L.1; Wang Z.1; Zhou J.1; Wu X.1; Wu J.1; Li W.1,2; Liang G.1
发表日期	2016-12
发表期刊	RUSSIAN JOURNAL OF GENERAL CHEMISTRY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	antitumor activity design and synthesis FGFR1 inhibitors gastric cancer NDGA analogs non-ATP-competitive protein kinase inhibitor
其他关键词	MONO-CARBONYL ANALOGS ; SQUAMOUS-CELL CARCINOMA ; AMPLIFICATION ; FGFR1
摘要	Fibroblast growth factor receptor 1 (FGFR1) is considered a therapeutic target for multiple cancers, including gastric cancer. FGFR1 inhibitors, being ATP competitors, can prevent the kinase domain and the downstream signaling cascade from phosphorylation and thus have the potential to treat cancers associated with aberrant FGFR1 activation. However, untargeted inhibition may cause numerous side effects. Thus, a non-ATP competitive FGFR1 inhibitor should be urgently identified and explored. In this study, we designed and synthesized 17 derivatives of nordihydroguaiaretic acid (NDGA), a known ATP-independent FGFR3 inhibitor. In the kinase activity assay, 3,5-bis(2-fluorobenzylidene)piperidin-4-one (1B) showed the highest kinase inhibitory activity among all derivatives and was thus identified as a non-ATP-competitive FGFR1 inhibitor. In the biological effect evaluation, 1B restrained the FGFR-FRS2-ERK signaling pathway in a dose-dependent manner and inhibited the growth of two gastric cancer cell lines. Overall, 1B can be considered as a potential candidate for treating gastric cancer and as an outstanding lead compound for the discovery of novel non-ATPcompetitive FGFR1 inhibitors.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81402839, 81272462]; ZheJiang Province Natural Science Funding of China [LY17H160059, LY13H300005]; Technology Foundation for Medical Science of Zhejiang Province [2012KYA129]; Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Jinan University; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities; Guangdong Provincial Thousand-Hundred-Ten Talent Project; University Students in Zhejiang Science and Technology Innovation Projects [2013R413023, 2015R413051]
出版者	MAIK NAUKA/INTERPERIODICA/SPRINGER
出版地	NEW YORK
ISSN	1070-3632
EISSN	1608-3350
卷号	86 期号:12 页码:2744-2751
DOI	10.1134/S1070363216120355
页数	8
WOS类目	Chemistry, Multidisciplinary
WOS研究方向	Chemistry
WOS记录号	WOS:000397491800035
收录类别	SCIE ; SCOPUS ; IC
URL	查看原文
SCOPUSEID	2-s2.0-85015379838
通讯作者地址	[Wu J.]Chemical Biology Research Center,College of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,325035,China
Scopus学科分类	Chemistry (all)
引用统计	被引频次：3[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/19187
专题	药学院（分析测试中心）药学院（分析测试中心）_生物有机与药物化学研究中心第一临床医学院（信息与工程学院）、附属第一医院_计算机与信息管理系
通讯作者	Wu J.
作者单位	1.Chemical Biology Research Center,College of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,325035,China; 2.College of Information Science and Computer Engineering,Wenzhou Medical University,Wenzhou,325035,China
第一作者单位	生物有机与药物化学研究中心
通讯作者单位	生物有机与药物化学研究中心
第一作者的第一单位	生物有机与药物化学研究中心
推荐引用方式 GB/T 7714	Ying S.,Wang, Jia,Xu C.,et al. Design, synthesis, and antiproliferative activity assessment of non-ATP-competitive fibroblast growth factor receptor 1 inhibitors[J]. RUSSIAN JOURNAL OF GENERAL CHEMISTRY,2016,86(12):2744-2751.
APA	Ying S.., Wang, Jia., Xu C.., Kang Y.., Zhang X.., ... & Liang G.. (2016). Design, synthesis, and antiproliferative activity assessment of non-ATP-competitive fibroblast growth factor receptor 1 inhibitors. RUSSIAN JOURNAL OF GENERAL CHEMISTRY, 86(12), 2744-2751.
MLA	Ying S.,et al."Design, synthesis, and antiproliferative activity assessment of non-ATP-competitive fibroblast growth factor receptor 1 inhibitors".RUSSIAN JOURNAL OF GENERAL CHEMISTRY 86.12(2016):2744-2751.