Stemcell, 73452, SU9516

SU9516 is a specific inhibitor of cyclin-dependent kinases (CDKs) including CDK2, CDK1 and, to a lesser extent, CDK4 with IC₅₀ values of 22, 40, and 200 nM, respectively (Lane et al.). It competitively binds in the ATP binding pocket of CDK2 and CDK1 (Moshinsky et al.). It is highly selective and does not inhibit PKC, p38 MAPK, PDGFR or EGFR (IC₅₀ > 10 µM; Lane et al.).

CANCER RESEARCH

· Decreases proliferation in human colon carcinoma cell lines RKO and SW480, through inhibition of retinoblastoma protein (Rb) phosphorylation, resulting in increased Rb/E2F, cell-cycle arrest, and subsequent apoptosis (Lane et al.; Yu et al.).

· Induces mitochondrial injury, caspase activation and subsequent apoptosis through downregulated transcription of the antiapoptotic protein MCL-1 in U937, Jurkat, and HL-60 leukemia or lymphoma cell lines (Gao et al.).

· Induces apoptosis, alone or in combination with paclitaxel, in the inflammatory breast cancer cell line SUM149PT (Opyrchal et al.).