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Design, synthesis and biological evaluation of 7-((7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy)-2,3-dihydro-1H-inden-1-one derivatives as potent FAK inhibitors for the treatment of ovarian cancer.

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文献详情

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WOS体系：
Pubmed体系：

收录情况： ◇ SCIE

作者：
Wei Wei[a] ; Zhanzhan Feng[a] ; Zhihao Liu[a] ; Xinyue Li[a] ; Hualong He[a] ; Kai Ran[b] ; Yaojie Shi[a] ; Yongxia Zhu[c] ; Tinghong Ye[a] ; Chao Gao[d,e,*3] ; Ningyu Wang[f,*2] ; Luoting Yu[a,*1] ;
机构： [a]Laboratory of Emergency Medicine, Department of Emergency Medicine, Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China [b]College of Pharmacy, National & Local Joint Engineering Research Center of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, Chongqing University of Arts and Sciences, Chongqing, 402160, China [c]Department of Clinical Pharmacy, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610041, China [d]Laboratory of Human Diseases and Immunotherapies, West China Hospital, Sichuan University, Chengdu, 610041, China [e]Institute of Immunology and Inflammation, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China [f]School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, China
出处：
DOI： 10.1016/j.ejmech.2021.113978
ISSN：

关键词： FAK Kinase inhibitor Structure-activity relationship Ovarian cancer Anti-Tumor

摘要：
Focal adhesion kinase (FAK) promotes tumor progression by intracellular signal transduction and regulation of gene expression and protein turnover, which is a compelling therapeutic target for various cancer types, including ovarian cancer. However, the clinical responses of FAK inhibitors remain unsatisfactory. Here, we describe the discovery of FAK inhibitors using a scaffold hopping strategy. Structure-activity relationship (SAR) exploration identified 36 as a potent FAK inhibitor, which exhibited inhibitory activities against FAK signaling in vitro. Treatment with 36 not only decreased migration and invasion of PA-1 cells, but also reduced expression of MMP-2 and MMP-9. Moreover, 36 inhibited tumor growth and metastasis, and no obvious adverse effects were observed during the in vivo study. These results revealed the potential of FAK inhibitor 36 for treatment of ovarian cancer.Copyright © 2021 Elsevier Masson SAS. All rights reserved.

基金：
This work was supported by the National Natural Science Foundation of China, China (81903441), National S&TMajor Special Project on Major New Drug Innovations, China (2018ZX09201018), Sichuan University Postdoctoral Science Research Foundation, China (2020SCU12020), and Post-Doctor Research Project, West China Hospital, Sichuan University, China (2018HXBH009).
语种：
外文
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中科院(CAS)分区：
出版当年[2022]版：
大类 | 1 区 医学
小类 | 1 区 药物化学
最新[2023]版：
大类 | 2 区 医学
小类 | 1 区 药物化学
JCR分区：
出版当年[2022]版：
Q1 CHEMISTRY, MEDICINAL
最新[2023]版：
Q1 CHEMISTRY, MEDICINAL

影响因子： 最新[2023版] 最新五年平均 出版当年[2022版] 出版当年五年平均 出版前一年[2021版] 出版后一年[2023版]

第一作者：
第一作者机构： [a]Laboratory of Emergency Medicine, Department of Emergency Medicine, Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China
共同第一作者：
通讯作者：
通讯机构： [a]Laboratory of Emergency Medicine, Department of Emergency Medicine, Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China [d]Laboratory of Human Diseases and Immunotherapies, West China Hospital, Sichuan University, Chengdu, 610041, China [e]Institute of Immunology and Inflammation, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China [f]School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, China [*1]Laboratory of Emergency Medicine, Department of Emergency Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China. [*2]School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, China. [*3]Laboratory of Human Diseases and Immunotherapies, Institute of Immunology and Inflammation, Frontiers Science Center for Diseaserelated Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China.
推荐引用方式(GB/T 7714)：
Wei Wei,Zhanzhan Feng,Zhihao Liu,et al.Design, synthesis and biological evaluation of 7-((7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy)-2,3-dihydro-1H-inden-1-one derivatives as potent FAK inhibitors for the treatment of ovarian cancer.[J].EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY.2022,228:doi:10.1016/j.ejmech.2021.113978.
APA：
Wei Wei,Zhanzhan Feng,Zhihao Liu,Xinyue Li,Hualong He...&Luoting Yu.(2022).Design, synthesis and biological evaluation of 7-((7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy)-2,3-dihydro-1H-inden-1-one derivatives as potent FAK inhibitors for the treatment of ovarian cancer..EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,228,
MLA：
Wei Wei,et al."Design, synthesis and biological evaluation of 7-((7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy)-2,3-dihydro-1H-inden-1-one derivatives as potent FAK inhibitors for the treatment of ovarian cancer.".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 228.(2022)

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