VS-4718

PND-1186 is an orally available, potent and reversible inhibitor against focal adhesion kinase (FAK IC50 = 1.5 nM; 50 µM ATP) and FMS-like tyrosine kinase 3 (72% Flt3 & 62% FAK inhibition by 100 nM PND-1186) with much reduced or little potenty toward 32 other kinases. PND-1186 inhibits cellular FAK activation (FAK pY397 IC50 = 100 nM) and migration (by 45%; 1 µM PND-1186) in adherent murine breast carcinoma 4T1 cultures. PND-1186 suppresses 4T1 soft agar colony growth (0.1-1 µM) and murine ID8 ovarian carcinoma tumor growth in mice in vivo (0.5 mg/mL via drinking water with 5% sucrose).