Small molecule chloropyramine hydrochloride (C4) targets the binding site of focal adhesion kinase and vascular endothelial growth factor receptor 3 and suppresses breast cancer growth in vivo.

ABSTRACT: FAK is a tyrosine kinase that functions as a key orchestrator of signals leading to invasion and metastasis. Since FAK interacts directly with a number of critical proteins involved in survival signaling in tumor cells, we hypothesized that targeting a key protein-protein interface with druglike small molecules was a feasible strategy for inhibiting tumor growth. In this study, we targeted the protein-protein interface between FAK and VEGFR-3 and identified compound C4 (chloropyramine hydrochloride) as a drug capable of (1) inhibiting the biochemical function of VEGFR-3 and FAK, (2) inhibiting proliferation of a diverse set of cancer cell types in vitro, and (3) reducing tumor growth in vivo. Chloropyramine hydrochloride reduced tumor growth as a single agent, while concomitant administrat

SUBMITTER: Kurenova EV 

PROVIDER: S-EPMC2765121 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature