SNS-032(BMS-387032)

Cas No.:	345627-80-7
Chemical Name:	N-(5-((5-tert-butyloxazol-2-yl)methylthio)thiazol-2-yl)piperidine-4-carboxamide
Synonyms:	BMS-387032; SNS 032; SNS032; BMS 387032; BMS387032
SMILES:	N1CCC(C(NC2=NC=C(SCC3=NC=C(C(C)(C)C)O3)S2)=O)CC1
Formula:	C17H24N4O2S2
M.Wt:	380.53
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	SNS-032 (BMS-387032) is a selective inhibitor of?CDK2, CDK7, and CDK9 with?IC50s?of 38 nM, 62 nM and 4 nM, respectively.
In Vivo:	SNS-032 (15 mg/kg, i.p.) inhibits both xenografted BaF3-T674I cells and KBM5-T315I cells in vivo. SNS-032 abrogates the growth of tumors transplanted in nude mice with downregulation of T674I PDGFRα and T315I-Bcr-Abl[4].
In Vitro:	SNS-032 has low sensitivity to CDK1 and CDK4 with IC50 of 480 nM and 925 nM, respectively. SNS-032 effectively kills chronic lymphocytic leukemia cells in vitro regardless of prognostic indicators and treatment history. Compared with flavopiridol and roscovitine, SNS-032 is more potent, both in inhibition of RNA synthesis and at induction of apoptosis. SNS-032 activity is readily reversible; removal of SNS-032 reactivates RNA polymerase II, which led to resynthesis of Mcl-1 and cell survival[1]. SNS-032 inhibits three dimensional capillary network formations of endothelial cells. SNS-032 completely prevents U87MG cell–mediated capillary formation of HUVECs. In addition, SNS-032 significantly prevents the production of VEGF in both cell lines, SNS-032 prevents in vitro angiogenesis, and this action is attributable to blocking of VEGF. Preclinical studies have shown that SNS-032 induces cell cycle arrest and apoptosis across multiple cell lines[2]. SNS-032 blocks the cell cycle via inhibition of CDKs 2 and 7, and transcription via inhibition of CDKs 7 and 9. SNS-032 activity is unaffected by human serum[3]. SNS-032 induces a dose-dependent increase in annexin V staining and caspase-3 activation. At the molecular level, SNS-032 induces a marked dephosphorylation of serine 2 and 5 of RNA polymerase (RNA Pol) II and inhibits the expression of CDK2 and CDK9 and dephosphorylated CDK7[5].