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

Abstract:

: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.

journal_name

Acta Pharmacol Sin

authors

Chen Z,Tong LJ,Tang BY,Liu HY,Wang X,Zhang T,Cao XW,Chen Y,Li HL,Qian XH,Xu YF,Xie H,Ding J

doi

10.1038/s41401-018-0191-7

subject

Has Abstract

pub_date

2019-06-01 00:00:00

pages

823-832

issue

6

eissn

1671-4083

issn

1745-7254

pii

10.1038/s41401-018-0191-7

journal_volume

40

pub_type

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