Uses
Cell permeable, potent, selective and ATP-competitive inhibitor of CDK2/cyclin A (IC50=22nM), CDK1/cyclin B (IC50=40nM) and CDK4/cyclin D1 (IC50=200nM). Has no effect on the activity of PKC, p38, PDGFRβ and EGFR (IC50>10μM). Displays anti-proliferative and pro-apoptotic properties in tumor cells. Inhibits proliferation of growth factor-stimulated colon carcinoma cells by binding to CDK2 and thus preventing the phosphorylation of pRb and its dissociation from E2F.
Definition
ChEBI: 3-(1H-imidazol-5-ylmethylidene)-5-methoxy-1H-indol-2-one is a member of indoles.
Biological Activity
Potent, selective cdk2 inhibitor (IC 50 values are 0.022, 0.04, >10, >10, 18 and >100 μ M for cdk2, cdk1, cdk4, PKC, p38, PDGFR and EGFR respectively). Inhibits pRb phosphorylation causing enhanced pRB/E2F complex formation and induces G 1 and G 2 -M cell cycle arrest. Transcriptionally downregulates Mcl-1 and has antiproliferative, cytostatic and pro-apoptotic effects in vitro .
IC 50
CDK2: 22 nM (IC50); CDK1: 40 nM (IC50); CDK4: 200 nM (IC50); PDGFr: 18000 nM (IC50)
References
[1]. lane me, yu b, rice a, et al. a novel cdk2-selective inhibitor, su9516, induces apoptosis in colon carcinoma cells. cancer res, 2001, 61(16): 6170-6177.
[2]. yu b, lane me, wadler s. su9516, a cyclin-dependent kinase 2 inhibitor, promotes accumulation of high molecular weight e2f complexes in human colon carcinoma cells. biochem pharmacol, 2002, 64(7): 1091-1100.
[3]. gao n, kramer l, rahmani m, et al. the three-substituted indolinone cyclin-dependent kinase 2 inhibitor 3-[1-(3h-imidazol-4-yl)-meth-(z)-ylidene]-5-methoxy-1,3-dihydro-indol-2-one (su9516) kills human leukemia cells via down-regulation of mcl-1 through a transcriptional mechanism. mol pharmacol, 2006, 70(2): 645-655.
