|SNS-032 (BMS-387032)CDK inhibitor|
Sample solution is provided at 25 µL, 10mM.
Publications citing ApexBio Products
|Description||SNS-032 is a selective inhibitor of CDK2 with IC50 of 48 nM.|
|IC50||48 nM||62 nM||4 nM|
|Cas No.||345627-80-7||SDF||Download SDF|
|Solubility||Soluble in DMSO > 10 mM||Storage||Store at -20°C|
|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.|
|Shipping Condition||Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request
SNS-032, a CDK inhibitor, exhibited modest to high anti-neuroblastoma activity against a panel of 109 neuroblastoma cell lines in the range of the therapeutic plasma levels reported for SNS-032 through a mechanism involving CDK7 and CDK9 inhibition-mediated down-regulation of XIAP, Mcl-1, BIRC2, cIAP-1 and surviving.
The anti-AML mechanism of SNS-032, a cyclin-dependent kinase inhibitor, has been identified though characterizing in vitro effects of SNS-032 alone or in combination with perifosine.
Although it induces apoptosis in cancer cells, SNS-032 has no significant effects on normal HSC and HPC in terms of self-renewal inhibition, differentiation suppression and apoptosis induction.
The CDK7/9 inhibitor SNS-032-induced down-regulation of FIP1L1-PDGFRα and Bcr-Abl has the potential to be used to decrease the acquired resistant to imatinib.
SNS-032, a CDK inhibitor, alone or in combination with Ara-C exhibited potent anti-AML activity, where down-regulation of antiapoptotic genes, cluding BCL2, XIAP amd MCL1, was associated with the synergistic anti-AML effect of the combination treatment.
SNS-032 (BMS-387032) is a potent and selective inhibitor of cyclin-dependent kinases (CDKs) 2, 7, and 9 , with IC50 values of 38 nM, 62 nM and 4 nM, respectively .
CDKs mean a family of serine/threonine kinases regulating cell cycle process. Some CDKs are related to transcription control and are often perturbed in cancer cells .
Decrease in the phosphorylation at Ser5 and Ser2 in the C-terminal domain (CTD) of RNA Pol II can indicate the inhibition to CDK9 and CDK7 . Chronic lymphocytic leukemia (CLL) cells treated with SNS-032 for 6 or 24 hours showed a decrease in the phosphorylation of Ser2 and Ser5 of the CTD of RNA Pol II, this appeared to be both time- and concentration- dependent, and remarkably consistent among samples. For the phosphorylation of Ser2, the inhibition of SNS-032 was greater than that for the phosphorylation of Ser5, this was consistent with the fact that IC50 for the inhibition of CDK9 was lower compared with that for the inhibition of CDK7 (4 nM vs 62 nM). After 6 hours of SNS-032 exposure, protein levels of CDK7 and CDK9 were stable, but declined at 24 hours .
In patients with chronic lymphocytic leukemia (CLL), infusion of SNS-032 in a total dose of 75 mg/m2 resulted in a decrease in the phosphorylation at Ser5 and Ser2 in the C-terminal domain of RNA Pol II. This indicated the inhibition to Cdk9 and Cdk7 by SNS-032. This inhibition was first seen 2 hours after the beginning of the infusion with SNS-032, was pronounced after 6 hours and returned to baseline after 24 hours .
. Tong W.G., Chen R., Plunkett W., et al. Phase I and Pharmacologic Study of SNS-032, a Potent and Selective Cdk2, 7, and 9 Inhibitor, in Patients With Advanced Chronic Lymphocytic Leukemia and Multiple Myeloma. Journal of Clinical Oncology, 2010, 28(18):3015- 3022.
. Chipumuro E., Marco E., Christensen C.L., et al. CDK7 Inhibition Suppresses Super-Enhancer-Linked Oncogenic Transcription in MYCN-Driven Cancer. Cell, 2014, 159:1-14.
. Meng H., Jin Y.M., Liu H., et al. SNS-032 inhibits mTORC1/mTORC2 activity in acute myeloid leukemia cells and has synergistic activity with perifosine against Akt. Journal of Hematology & Oncology, 2013, 6:18.
. Chen R., Wierda W.G., Chubb S., et al. Mechanism of action of SNS032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. Blood, 2009, 113(19):4637-4645.