SNS-032 (BMS-387032)

For research use only.

Catalog No.S1145

60 publications

SNS-032 (BMS-387032) Chemical Structure

CAS No. 345627-80-7

SNS-032 (BMS-387032) has firstly been described as a selective inhibitor of CDK2 with IC50 of 48 nM in cell-free assays and is 10- and 20-fold selective over CDK1/CDK4. It is also found to be sensitive to CDK7/9 with IC50 of 62 nM/4 nM, with little effect on CDK6. SNS-032 (BMS-387032) induces apoptosis. Phase 1.

Selleck's SNS-032 (BMS-387032) has been cited by 60 publications

Purity & Quality Control

Choose Selective CDK Inhibitors

Biological Activity

Description SNS-032 (BMS-387032) has firstly been described as a selective inhibitor of CDK2 with IC50 of 48 nM in cell-free assays and is 10- and 20-fold selective over CDK1/CDK4. It is also found to be sensitive to CDK7/9 with IC50 of 62 nM/4 nM, with little effect on CDK6. SNS-032 (BMS-387032) induces apoptosis. Phase 1.
Targets
CDK9/CyclinT [3]
(Cell-free assay)
CDK2/CyclinA [3]
(Cell-free assay)
CDK2/CyclinE [1]
(Cell-free assay)
CDK7/CyclinH [3]
(Cell-free assay)
GSK-3α [3]
(Cell-free assay)
4 nM 38 nM 48 nM 62 nM 230 nM
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. [4]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human A2780 cell line NF;MPXdRem:uaX\ldoF1cW:wIHHzd4F6 M4DTfVczKGh? MnrKRY51cXC{b3zp[oVz[XSrdnWg[YZn\WO2IHHnZYlve3RiaIXtZY4hSTJ5OECgZ4VtdCCuaX7lJJdieyCmZYTldo1qdmWmIHnuJIEhf2ixbHWgZ4VtdCB5MjDodkBkgXSxdH;4bYNqfHliYYPzZZktKEmFNUC9PVUhdk1? MofTQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTVyMke4OlMoRjF3MEK3PFY{RC:jPh?=
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Rh41 NVzGN|F[eUiWUzDhd5NigQ>? NFf0WZByUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBTcDRzIHPlcIx{ NIfZUVA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
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... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
p-RNA PolII / RNA Pol II / CDK7 / CDK9 ; 

PubMed: 31526394     


SNS-032 inhibited CTD phosphorylation of RNA Pol II in UM cells. Cells were treated with increasing concentration of SNS-032 for 48 h, Western blot analysis with the indicated antibodies was performed.

YAP / p-YAP / CTGF / CYR61 ; 

PubMed: 31526394     


SNS-032 blocked YAP signaling in UM cells. Mel270 and Omm2.3 cells were treated with SNS-032 for 48 h, the protein levels of YAP, phospho-YAP (S127) and its downstream targets CTGF and CYR61 were examined by Western blot analysis. 

p-ROCK / ROCK / p-LIMK1/2 / LIMK1/2 / p-Cofilin / Cofilin ; 

PubMed: 31526394     


SNS-032 inhibited the RhoA-ROCK-LIMK1/2-cofilin pathway. Mel270 and Omm2.3 cells were treated with increasing concentrations of SNS-032 for 48 h, and then subjected to Western blot analysis with the indicated antibodies.

Mcl-1 / Cyclin D1 / Bcl-2 / PARP ; 

PubMed: 20663900     


SNS-032 reduced the protein levels of Mcl-1 and cyclin D1 and induced apoptosis.

31526394 20663900
Growth inhibition assay
Cell viability; 

PubMed: 20663900     


SNS-032 inhibited proliferation of the four MCL cell lines. MCL cells were seeded on 24 well plates, SNS-032 at concentrations of 0 (○), 0.03, (●), 0.1 (◆), 0.3 (▼), 1 (▲) and 3 (■) μM were added the next day. Cell concentrations were measured at 24, 48 and 72 h after addition of SNS-032. Data (mean +/− SD) represent percentage of cell growth compared to day 1 of three independent experiments.

20663900
In vivo SNS-032 prevents tumor cell-induced VEGF secretion in a tumor coculture model. [2] SNS-032, a new CDK inhibitor, is more selective and less cytotoxic and has been shown to prolong stable disease in solid tumors. [4]

Protocol

Cell Research:[2]
- Collapse
  • Cell lines: HUVECs and U87MG cells
  • Concentrations: 0–0.5 mM
  • Incubation Time: 24, 48, or 72 hours
  • Method: Cell Titer-Glo (CTG) luminescent assay is performed to measure the growth curves of both HUVECs and U87MG cells. U87MG cells and HUVECs (2×103 cells/well) are seeded in a 96-well microplate in a final volume of 100 ml. After 24 hours, cells are treated with various doses of SNS-032 (0–0.5 mM) for 24, 48, or 72 hours. After completion of the treatment, 100 ml of CTG solution is added to each well and incubated for 20 minutes at room temperature in the dark. Lysate (50 ml) is transferred to a 96-well white plate, and luminescence is measured by POLARstar OPTIMA. Percent cell growth is calculated by considering 100% growth at the time of SNS-032 addition.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 76 mg/mL (199.72 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
30% PEG400+0.5% Tween80+5% propylene glycol
For best results, use promptly after mixing.
30 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 380.53
Formula

C17H24N4O2S2

CAS No. 345627-80-7
Storage powder
in solvent
Synonyms N/A
Smiles CC(C)(C)C1=CN=C(O1)CSC2=CN=C(S2)NC(=O)C3CCNCC3

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
Dosage mg/kg Average weight of animals g Dosing volume per animal ul Number of animals
Step 2: Enter the in vivo formulation ()
% DMSO % % Tween 80 % ddH2O
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Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

  • Mass
    Concentration
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    Molecular Weight

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and SDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

  • C1
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    C2
    V2

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / COA (available online).

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
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    C8=C7/X C8: LOG(C8):
Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT00446342 Completed Drug: SNS-032 Injection B-lymphoid Malignancies|Chronic Lymphocytic Leukemia|Mantle Cell Lymphoma|Multiple Myeloma Sunesis Pharmaceuticals February 2007 Phase 1

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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CDK Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID