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

Authors: Zhuo Chen1,2, Lin-jiang Tong1, Bai-you Tang1, Hong-yan Liu1, Xin Wang2, Tao Zhang1, Xian-wen Cao2, Yi Chen1, Hong-lin Li2, Xu-hong Qian2, Yu-fang Xu2, Hua Xie1, Jian Ding1
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
Correspondence to: Yu-fang Xu:, Hua Xie:, Jian Ding:,
DOI: 10.1038/s41401-018-0191-7
Received: 21 August 2018
Accepted: 22 October 2018
Advance online: 28 November 2018


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 FGFR1 inhibitor with an IC50 of 19 nM among a panel of 20 tyrosine 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.
Keywords: C11; FGFR1 inhibitor; antitumor; breast cancer; metastasis; angiogenesis

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