SNS-032

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

SNS-032 (BMS-387032) 是一种有效的选择性 CDK 2/7/9 抑制剂，IC50 分别为 48 nM/62 nM/4 nM。

SNS-032 (BMS-387032)?is a potent and selective inhibitor of CDK 2/7/9 with IC50 of 48 nM/62 nM/4 nM, respectively; displays 10- and 20-fold selective over CDK1/cycB and CDK4/cycD (IC50=480 and 925 nM) respectively, and a panel of unrelated kinases, respectively; blocks the cell cycle via inhibition of CDKs 2 and 7, and transcription via inhibition of CDKs 7 and 9, has an A2780 cellular cytotoxicity assay IC50 of 95 nM; exhibits a efficacy profile in A2780 human ovarian carcinoma xenograft model.Blood Cancer,Phase 2 Discontinued(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. 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. 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. 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.(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.

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. 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. 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. 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.

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.

BMS-387032

Cell Cycle/DNA Damage

CDK

CDK2/CyclinA|CDK2/CyclinE|CDK7/CyclinH|CDK9/CyclinT|GSK-3α

Cancer

Blood cancer

345627-80-7

380.528

C17H24N4O2S2

>98% (HPLC)

10 mM in DMSO

CC(C)(C)C1=CN=C(CSC2=CN=C(NC(=O)C3CCNCC3)S2)O1 |t:4,6,10,12|

4-Piperidinecarboxamide, N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-

(-20℃)

With Ice Pack

≥ 2 years