General Description
An orally bioavailable oxindolo-furanyl compound that acts as a potent, reversible and ATP-competitive inhibitor of pan PIM-kinases (IC
50 = 5, 25 and 16 nM for PIM-1, PIM-2 and PIM-3, respectively; K
i = 5 nM for PIM-1) with excellent selectivity over 107 kinases (IC
80 >500 nM). Shown to arrest the proliferation of several human cancer cells (IC
50 = 20 and 452 nM for MV-4-11 and PC3 cells) and block phosphorylation of Bad-Ser
112, 4E-BP1-Ser
65 and Thr
37/46 with an IC
50 of ~ 1.0 μM. Displays favorable pharmacokinetic profile and efficacy in mice, and suppresses tumor growth in MV-4-11 and PC3 xenograft murine model (50 mg/kg, p.o.). Further, potentiates doxorubicin (Cat. No.
324380) and paclitaxel (Cat. No.
580555) toxicity in PC3 cells.
