SNS-032

SNS-032 (formerly BMS-387032) is a small-molecule cyclin-dependent kinases (CDK) inhibitor. SNS-032 arrests the cell cycle at G2/M; inhibits transcription, proliferation and colony formation, and induces apoptosis in RPMI-8226 multiple myeloma cells. SNS-032 (BMS-387032) prevents tumor cell-induced VEGF secretion and in vitro angiogenesis. SNS-032-induced a dose-dependent increase in annexin V staining and caspase-3 activation. At the molecular level, SNS-032 induced a marked dephosphorylation of serine 2 and 5 of RNA polymerase (RNA Pol) II and inhibited the expression of CDK2 and CDK9 and dephosphorylated CDK7. SNS-032 effectively killed chronic lymphocytic leukemia cells in vitro. At the dose levels tested, the oral bioavailability of SNS-032 ranged from 4-33%. SNS-032 is currently in phase I clinical trials for the treatment of B-cell malignancies and advanced solid tumors.