SU 9516 is a selective and novel inhibitor of CDK2 with IC50 value of 22 nM. Also, it inhibits CDK1, CDK4, PKC, p38, PDGFR with IC50 value of 0.04, 0.2, >10.0, >10.0, 18.0 μM, respectively .
Cyclin-dependent kinase 2 (CDK2) is a member of the cyclin-dependent kinase family and is a catalytic subunit of the cyclin-dependent kinase complex Cyclin E/CDK2 or Cyclin A/CDK2, which play an important role in the G1-S phase of the cell cycle .
In RKO cells, SU 9516 (5 μM) decreased cdk2-specific phosphorylation of pRb by 52%. While, in SW480 cells, SU9516 (5 μM) inhibited both cdk2-specific and cdk4-specific phosphorylation of pRb by 64% and 49%, respectively. Also, SU 9516 (5 μM) resulted in G0-G1 or G2-M block and induced apoptosis in a dose-dependent way . In HT-29, SW480 and RKO human colon cancer cells, SU9516 (5 μM) inhibited dissociation of pRb from E2F1 in a time-dependant way. Also, SU 9516 decreased Cyclin D1 and CDK2 by 10-60% . In human leukemia cells, SU 9516 (5 μM) induced Bax mitochondrial translocation, cytochrome c release and apoptosis, which were associated with down-regulation of the antiapoptotic protein Mcl-1. Also, SU 9516 induced activation of caspase-3 and -8 .
. 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.
. 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.
. 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.
|Storage||Store at 4°C|
|Solubility||Soluble in DMSO|
|Shipping Condition||Evaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request|
|General tips||For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.|