文献类型：期刊文献

中文题名：C11 , a novel fibroblast growth factor receptor 1 (FGFR1) inhibitor, suppresses breast cancer metastasis and angiogenesis

作者：Zhuo Chen[1,2];Lin-jiang Tong[1];Bai-you Tang[1];Hong-yan Liu[1];Xin Wang[2];Tao Zhang[1];Xian-wen Cao[2];Yi Chen[1];Hong-lin Li[2];Xu-hong Qian[2];Yu-fang Xu[2];Hua Xie[1];Jian Ding[1]

机构：[1]Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;[2]Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China

年份：2019

卷号：40

期号：6

起止页码：823

中文期刊名：Acta Pharmacologica Sinica

外文期刊名：中国药理学报（英文版）

收录：CSTPCD;;Scopus;CSCD:【CSCD2019_2020】；PubMed;

基金：National Natural Science Foundation of China (grants 81173080, 81321092, 21236002 and 21302054);National Basic Research Program of China (973 Program, 2010CB126100);National High Technology Research and Development Program of China (863 Program, 2011AA10A207);National Science & Technology Pillar Program (2009ZX09103-102);Shanghai Committee of Science and Technology (grant 13ZR1453100);Fundamental Research Funds for the Central Universities.

语种：英文

中文关键词：C11;FGFR1;inhibitor;antitumor;breast;cancer;metastasis;angiogenesis

摘要：The fibroblast growth factor receptors (FGFRs) are increasingly considered attractive targets for therapeutic cancer intervention due to their roles in tumor metastasis and angiogenesis. Here, we identified a new selective FGFR inhibitor, C11, and assessed its antitumor activities. C11 was a selective FGFftl inhibitor with an IC50 of 19 nM Hrnony a panel of 20 tyrnsine kinases. C11 inhibited cell proliferation in various tumors, particularly bladder cancer and breast cancer. C11 also inhibited breast cancer MDA MB 231 cell migration and invasion via suppression of FGFR1 phosphorylation and its downstream signaling pathway. Suppression of matrix metalloproteinases 2/9 (MMP2/9) was associated with the anti-motility activity of C11. Furthermore, the anti-angiogenesis activity of C11 was verified in endothelial cells and chicken chorioallantoic membranes (CAMs). C11 inhibited the migration and tube formation of HMEC-1 endothelial cells and inhibited angiogenesis in a CAM assay. In sum, C11 is a novel selective FGFR1 inhibitor that exhibits potent activity against breast cancer metastasis and angiogenesis.