VS-4718 (PND-1186) is a potent, highly-specific and reversible inhibitor of FAK with IC50 of 1.5 nM, promotes tumor cell apoptosis. VS-4718 has an IC50 of ~100 nM in breast carcinoma cells as determined by anti-phospho-specific immunoblotting to FAK Tyr-397. VS-4718 (0.1 uM) blocks FAK and p130Cas tyrosine phosphorylation, promotes caspase-3 activation, and triggers cell apoptosis. VS-4718 inhibits 4T1 breast carcinoma subcutaneous tumor growth correlated with elevated tumor cell apoptosis and caspase 3 activation. VS-4718 (150 mg/kg, oral) decreases tumor growth and spontaneous breast to lung metastasis in pre-clinical models.
