U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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
Structure of SNS-032

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)

HIDE SMILES / InChI

Molecular Formula C17H24N4O2S2
Molecular Weight 380.528
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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.

CNS Activity

Curator's Comment: Brain penetration studies in mice showed brain levels of BMS-387032 (SNS-032) about 3.5-fold higher in P-glycoprotein knockout mice than in wildtype mice, providing evidence of BMS-387032 being a P-glycoprotein substrate. No human data available.

Originator

Curator's Comment: # Bristol-Myers Squibb

Approval Year

Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
0.017 μg/mL
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
0.052 μg × h/mL
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
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

T1/2

ValueDoseCo-administeredAnalytePopulation
8.5 h
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
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

Funbound

ValueDoseCo-administeredAnalytePopulation
37%
unknown, unknown
SNS-032 serum
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
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
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
SNS-032 prevents hypoxia-mediated glioblastoma cell invasion by inhibiting hypoxia inducible factor-1alpha expression.
2009 Apr
Responses in mantle cell lymphoma cells to SNS-032 depend on the biological context of each cell line.
2010 Aug 15
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

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
Treatment of RPMI-8226 MM cells with 300 nM SNS-032 (IC(90)) for 6 h was sufficient for commitment to apoptosis. Antiproliferative activity was established in an A2780 cellular cytotoxicity assay in which SNS-032 showed an IC(50) = 95 nM.
Substance Class Chemical
Created
by admin
on Fri Dec 15 19:22:14 GMT 2023
Edited
by admin
on Fri Dec 15 19:22:14 GMT 2023
Record UNII
9979I93686
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
SNS-032
Common Name English
BMS387032
Common Name English
N-(5-(((5-(1,1-DIMETHYLETHYL)-2-OXAZOLYL)METHYL)THIO)-2-THIAZOLYL)-4-PERIDINECARBOXAM
Common Name English
BMS-387032
Common Name English
SNS 032 [WHO-DD]
Common Name English
4-PIPERIDINECARBOXAMIDE, N-(5-(((5-(1,1-DIMETHYLETHYL)-2-OXAZOLYL)METHYL)THIO)-2-THIAZOLYL)-
Systematic Name English
Code System Code Type Description
FDA UNII
9979I93686
Created by admin on Fri Dec 15 19:22:14 GMT 2023 , Edited by admin on Fri Dec 15 19:22:14 GMT 2023
PRIMARY
DRUG BANK
DB05969
Created by admin on Fri Dec 15 19:22:14 GMT 2023 , Edited by admin on Fri Dec 15 19:22:14 GMT 2023
PRIMARY
CAS
345627-80-7
Created by admin on Fri Dec 15 19:22:14 GMT 2023 , Edited by admin on Fri Dec 15 19:22:14 GMT 2023
PRIMARY
ChEMBL
CHEMBL296468
Created by admin on Fri Dec 15 19:22:14 GMT 2023 , Edited by admin on Fri Dec 15 19:22:14 GMT 2023
PRIMARY
CHEBI
91399
Created by admin on Fri Dec 15 19:22:14 GMT 2023 , Edited by admin on Fri Dec 15 19:22:14 GMT 2023
PRIMARY
PUBCHEM
3025986
Created by admin on Fri Dec 15 19:22:14 GMT 2023 , Edited by admin on Fri Dec 15 19:22:14 GMT 2023
PRIMARY
EPA CompTox
DTXSID50188100
Created by admin on Fri Dec 15 19:22:14 GMT 2023 , Edited by admin on Fri Dec 15 19:22:14 GMT 2023
PRIMARY
NCI_THESAURUS
C62523
Created by admin on Fri Dec 15 19:22:14 GMT 2023 , Edited by admin on Fri Dec 15 19:22:14 GMT 2023
PRIMARY
Related Record Type Details
TARGET->WEAK INHIBITOR
IC50
TARGET -> INHIBITOR
IC50
TARGET -> INHIBITOR
IC50
TARGET -> INHIBITOR
IC50
TARGET->WEAK INHIBITOR
IC50
Related Record Type Details
ACTIVE MOIETY