D-Cyclins regulate the cell cycle by acting in a complex with cyclin dependent kinases (CDKs) to promote phosphorylation of the retinoblastoma protein and initiate cellular progression from the G1 to the S phase. Cell cycle deregulation in many cancers often results from altered cyclin D/CDK activity. S14161 is a small molecule inhibitor of cyclins D1-D3 expression that inhibits phosphoinositide 3-kinase activity and arrests cells at the G0/G1 phase in a dose-dependent manner (concentrations tested from 5-10 μM). S14161 induces apoptosis in myeloma and leukemia cell lines (IC50s 25 μM). In a mouse model of leukemia, S14161 delayed tumor growth by up to 90% compared to controls at a dose of 100 mg/kg/day.