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

C11, a novel fibroblast growth factor receptor 1 (FGFR1) inhibitor, suppresses breast cancer metastasis and angiogenesis. Acta Pharmacol Sin. 2018 Nov 28;: 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 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. PMID: 30487650 [PubMed - as supplied by publisher]
Source: Acta Pharmacologica Sinica - Category: Drugs & Pharmacology Authors: Tags: Acta Pharmacol Sin Source Type: research