Home Cell Cycle CDK inhibitor SNS-032 (BMS-387032)

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SNS-032 (BMS-387032) CDK inhibitor

Cat.No.S1145

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. This compound induces apoptosis.
SNS-032 (BMS-387032) CDK inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 380.53

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Quality Control

Batch: Purity: 99.75%
99.75

Cell Culture, Treatment & Working Concentration

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human A2780 cell line Proliferation assay 72 h Antiproliferative effect against human A2780 cell line was determined in a whole cell 72 hr cytotoxicity assay, IC50=95 nM 15027863
Sf21 Function assay Inhibition of recombinant human full length C-terminal His6-tagged CDK9/cyclin T1 expressed in baculovirus infected Sf21 insect cells using PDKtide as substrate, IC50=0.004μM 27171036
Sf21 Function assay Inhibition of human full length C-terminal His6-tagged CDK2/N-terminal GST-tagged cyclin A expressed in baculovirus infected Sf21 insect cells using histone H1 as substrate, IC50=0.038μM 27171036
Sf21 Function assay Inhibition of recombinant human full length C-terminal His6-tagged CDK2/N-terminal GST-tagged cyclin E expressed in baculovirus infected Sf21 insect cells using histone H1 as substrate, IC50=0.048μM 27171036
Sf21 Function assay Inhibition of recombinant human full length C-terminal His6-tagged CDK7/cyclin H/N-terminal GST-tagged MAT1 expressed in baculovirus infected Sf21 insect cells using cdk7 substrate peptide, IC50=0.062μM 27171036
Sf21 Function assay Inhibition of recombinant human full length N-terminal His6-tagged CDK5/N-terminal GST-tagged p25 expressed in baculovirus infected Sf21 insect cells using histone H1 as substrate, IC50=0.34μM 27171036
HCT116 Function assay 16 hrs Inhibition of CDK9 in human HCT116 cells assessed as phosphor-ser2 level of RNA polymerase 2 after 16 hrs by high content cellular assay, IC50=0.458μM 18842409
Sf21 Function assay Inhibition of human full length C-terminal His6-tagged CDK1/N-terminal GST-tagged cyclin B expressed in baculovirus infected Sf21 insect cells using histone H1 as substrate, IC50=0.48μM 27171036
HCT116 Function assay 16 hrs Inhibition of CDK9-mediated RNA pol 2 phosphorylation at ser2 in human HCT116 cells after 16 hrs by HCS assay, IC50=0.55μM 18926699
HCT116 Antiproliferative assay 24 hrs Antiproliferative activity against human HCT116 cells after 24 hrs by MTT assay, IC50=0.7μM 30197029
Sf cells Function assay Inhibition of recombinant human N-terminal GST-tagged CDK4/cyclin D1 expressed in baculovirus infected sf cells, IC50=0.925μM 27171036
MCF7 Antiproliferative assay 24 hrs Antiproliferative activity against human MCF7 cells after 24 hrs by MTT assay, IC50=1μM 30197029
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells) 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells 29435139
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for LAN-5 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells 29435139
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells 29435139
U-2 OS qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for OHS-50 cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells 29435139
Click to View More Cell Line Experimental Data

Solubility

In vitro
Batch:

DMSO : 76 mg/mL (199.72 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 30 mg/mL

Water : Insoluble

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Mass Concentration Volume Molecular Weight
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In vivo
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In vivo Formulation Calculator (Clear solution)

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Working concentration: mg/ml;

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Chemical Information, Storage & Stability

Molecular Weight 380.53 Formula

C17H24N4O2S2

 Storage (From the date of receipt)
CAS No. 345627-80-7 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles CC(C)(C)C1=CN=C(O1)CSC2=CN=C(S2)NC(=O)C3CCNCC3

Mechanism of Action

Targets/IC50/Ki
CDK9/CyclinT
(Cell-free assay)
4 nM
CDK2/CyclinA
(Cell-free assay)
38 nM
CDK2/CyclinE
(Cell-free assay)
48 nM
CDK7/CyclinH
(Cell-free assay)
62 nM
GSK-3α
(Cell-free assay)
230 nM
CDK5/p35
(Cell-free assay)
340 nM
In vitro

SNS-032 (BMS-387032) has low sensitivity to CDK1 and CDK4 with IC50 of 480 nM and 925 nM, respectively. This compound effectively kills chronic lymphocytic leukemia cells in vitro regardless of prognostic indicators and treatment history. Compared with flavopiridol and roscovitine, this agent is more potent, both in inhibition of RNA synthesis and at induction of apoptosis. Its activity is readily reversible; removal of this compound reactivates RNA polymerase II, which led to resynthesis of Mcl-1 and cell survival.

This inhibitor inhibits three dimensional capillary network formations of endothelial cells. It completely prevents U87MG cell–mediated capillary formation of HUVECs. In addition, this chemical significantly prevents the production of VEGF in both cell lines, it prevents in vitro angiogenesis, and this action is attributable to blocking of VEGF. Preclinical studies have shown that this compound induces cell cycle arrest and apoptosis across multiple cell lines.

This agent blocks the cell cycle via inhibition of CDKs 2 and 7, and transcription via inhibition of CDKs 7 and 9. Its activity is unaffected by human serum.

This compound induces a dose-dependent increase in annexin V staining and caspase-3 activation. At the molecular level, it 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 (BMS-387032) prevents tumor cell-induced VEGF secretion in a tumor coculture model.

This compound, a new CDK inhibitor, is more selective and less cytotoxic and has been shown to prolong stable disease in solid tumors.

References
  • [4] https://pubmed.ncbi.nlm.nih.gov/21212792/
  • [5] https://pubmed.ncbi.nlm.nih.gov/22447844/

Applications

Methods Biomarkers Images PMID
Western blot p-RNA PolII / RNA Pol II / CDK7 / CDK9 YAP / p-YAP / CTGF / CYR61 p-ROCK / ROCK / p-LIMK1/2 / LIMK1/2 / p-Cofilin / Cofilin Mcl-1 / Cyclin D1 / Bcl-2 / PARP
S1145-WB1
31526394
Growth inhibition assay Cell viability
S1145-viability1
20663900

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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

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