Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C17H24N4O2S2 |
| Molecular Weight | 380.528 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(C)(C)C1=CN=C(CSC2=CN=C(NC(=O)C3CCNCC3)S2)O1
InChI
InChIKey=OUSFTKFNBAZUKL-UHFFFAOYSA-N
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)
SNS-032 (formerly BMS-387032) is a potent, selective inhibitor of cyclin-dependent kinases (CDK). SNS-032 blocks the cell cycle via inhibition of CDKs 2 and 7, and transcription via inhibition of CDKs 7 and 9. SNS-032 was investigated for the treatment of solid tumors and hematologic malignancies (Phase I studies), however, its development was discontinued.
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL2094126 |
48.0 nM [IC50] | ||
Target ID: CHEMBL2111389 |
5.0 nM [Ki] | ||
Target ID: CHEMBL3038469 |
70.0 nM [Ki] | ||
| 60.0 nM [Ki] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Unknown Approved UseUnknown |
|||
| Primary | Unknown Approved UseUnknown |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
0.017 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17938863 |
16 mg/m² single, oral dose: 16 mg/m² route of administration: Oral experiment type: SINGLE co-administered: |
SNS-032 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
0.287 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17938863 |
16 mg/m² single, intravenous dose: 16 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
SNS-032 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
0.052 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17938863 |
16 mg/m² single, oral dose: 16 mg/m² route of administration: Oral experiment type: SINGLE co-administered: |
SNS-032 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
0.553 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17938863 |
16 mg/m² single, intravenous dose: 16 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
SNS-032 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
8.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17938863 |
16 mg/m² single, oral dose: 16 mg/m² route of administration: Oral experiment type: SINGLE co-administered: |
SNS-032 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
9.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17938863 |
16 mg/m² single, intravenous dose: 16 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
SNS-032 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
37% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15027863 |
unknown, unknown |
SNS-032 serum | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
PubMed
| Title | Date | PubMed |
|---|---|---|
| E2F4 deficiency promotes drug-induced apoptosis. | 2004 Dec |
|
| N-(cycloalkylamino)acyl-2-aminothiazole inhibitors of cyclin-dependent kinase 2. N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-4- piperidinecarboxamide (BMS-387032), a highly efficacious and selective antitumor agent. | 2004 Mar 25 |
|
| P-glycoprotein plays a role in the oral absorption of BMS-387032, a potent cyclin-dependent kinase 2 inhibitor, in rats. | 2005 Feb |
|
| Drugging cell cycle kinases in cancer therapy. | 2005 May |
|
| SNS-032 prevents tumor cell-induced angiogenesis by inhibiting vascular endothelial growth factor. | 2007 May |
|
| Transcriptional upregulation of p57 (Kip2) by the cyclin-dependent kinase inhibitor BMS-387032 is E2F dependent and serves as a negative feedback loop limiting cytotoxicity. | 2007 May 24 |
|
| Modifications of the isonipecotic acid fragment of SNS-032: analogs with improved permeability and lower efflux ratio. | 2008 Dec 1 |
|
| Transient treatment with CDK inhibitors eliminates proliferative potential even when their abilities to evoke apoptosis and DNA damage are blocked. | 2008 Dec 15 |
|
| A phase 1 study of SNS-032 (formerly BMS-387032), a potent inhibitor of cyclin-dependent kinases 2, 7 and 9 administered as a single oral dose and weekly infusion in patients with metastatic refractory solid tumors. | 2008 Feb |
|
| A diaminocyclohexyl analog of SNS-032 with improved permeability and bioavailability properties. | 2008 Nov 1 |
|
| SNS-032 prevents hypoxia-mediated glioblastoma cell invasion by inhibiting hypoxia inducible factor-1alpha expression. | 2009 Apr |
|
| Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. | 2009 May 7 |
|
| The small-molecule CDK inhibitor, SNS-032, enhances cellular radiosensitivity in quiescent and hypoxic non-small cell lung cancer cells. | 2009 Oct |
|
| SNS-032 is a potent and selective CDK 2, 7 and 9 inhibitor that drives target modulation in patient samples. | 2009 Sep |
|
| Responses in mantle cell lymphoma cells to SNS-032 depend on the biological context of each cell line. | 2010 Aug 15 |
|
| Phase I and pharmacologic study of SNS-032, a potent and selective Cdk2, 7, and 9 inhibitor, in patients with advanced chronic lymphocytic leukemia and multiple myeloma. | 2010 Jun 20 |
|
| Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. | 2010 Nov 24 |
|
| Comprehensive analysis of kinase inhibitor selectivity. | 2011 Oct 30 |
Patents
Sample Use Guides
Patients with metastatic solid tumors or refractory lymphoma were treated with a starting dose of 4 mg/m2 intravenously administered over 1-h with a cycle defined as 3 weekly doses of SNS-032 every 21 days. Three patient cohorts were utilized in the dose-escalation schema. Pharmacokinetic studies were performed. For the 13 and 16 mg/m2 dose cohorts, the first dose of cycle 2 was given as an oral solution to estimate the oral bioavailability of the drug in humans.
Route of Administration:
Other
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9979I93686
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DB05969
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345627-80-7
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CHEMBL296468
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91399
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3025986
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DTXSID50188100
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C62523
Created by
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ACTIVE MOIETY
