SNS-032

SNS-032 (BMS-387032) is a potent and selective inhibitor of CDK2, CDK7, and CDK9 with IC50s of 38 nM, 62 nM and 4 nM, respectively. SNS-032 has antitumor effect.

Product information

CAS Number: 345627-80-7

Molecular Weight: 380.53

Formula: C17H24N4O2S2

Synonym:

SNS 032

SNS032

BMS387032

BMS 387032

BMS-387032

Related CAS Number:

345627-90-9 (SNS-032 hydrochloride)

Chemical Name: N-(5-{[(5-tert-butyl-1, 3-oxazol-2-yl)methyl]sulfanyl}-1, 3-thiazol-2-yl)piperidine-4-carboxamide

Smiles: CC(C)(C)C1=CN=C(CSC2=CN=C(NC(=O)C3CCNCC3)S2)O1

InChiKey: OUSFTKFNBAZUKL-UHFFFAOYSA-N

InChi: InChI=1S/C17H24N4O2S2/c1-17(2,3)12-8-19-13(23-12)10-24-14-9-20-16(25-14)21-15(22)11-4-6-18-7-5-11/h8-9,11,18H,4-7,10H2,1-3H3,(H,20,21,22)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO: 76 mg/mL(199.72 mM). Water: Insoluble.

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

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 prevents tumor cell-induced VEGF secretion in a tumor coculture model. SNS-032, a new CDK inhibitor, is more selective and less cytotoxic and has been shown to prolong stable disease in solid tumors.

References:

1. Conroy A, et al. Cancer Chemother Pharmacol, 2009, 64(4), 723-32.
2. Ali MA, et al. Neoplasia, 2007, 9(5), 370-81.
3. Chen R, et al. Blood, 2009, 113(19): 4637-45.

Products are for research use only. Not for human use.