SU 9516

SU 9516 is a 3-substituted indolinone that has anti-proliferative and pro-apoptotic activity in tumor cells. It is a potent inhibitor of several cyclin-dependent kinases (CDKs) with selectivity for Cdk2 (IC50s = 22, 40, and 200 nM for Cdk2/cyclin A, Cdk1/cyclin B, and Cdk4/cyclin D1). It does not inhibit PKC, p38, PDGFR, or EGFR (IC50s = >10 µM). SU 9516 inhibits phosphorylation of the retinoblastoma protein pRb, resulting in increased pRb/E2F complex formation, cell-cycle arrest, and subsequent apoptosis. In leukemia cells (U937, Jurkat, and HL-60 cells) SU 9516 downregulates transcription of the antiapoptotic protein Mcl-1, leading to mitochondrial injury and cell death.InChI: InChI=1S/C13H11N3O2/c1-18-9-2-3-12-10(5-9)11(13(17)16-12)4-8-6-14-7-15-8/h2-7H,1H3,(H,14,15)(H,16,17)/b11-4- InChIKey: QNUKRWAIZMBVCU-WCIBSUBMSA-N SMILES: O=C1NC2=CC=C(OC)C=C2/C1=C/C3=CNC=N3