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.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15338193
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15027863
Curator's Comment: # Bristol-Myers Squibb
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2094126 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15027863 |
48.0 nM [IC50] | ||
Target ID: CHEMBL2111389 |
5.0 nM [Ki] | ||
Target ID: CHEMBL3038469 |
70.0 nM [Ki] | ||
Target ID: CHEMBL2111288 |
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 |
---|---|---|
SNS-032 prevents tumor cell-induced angiogenesis by inhibiting vascular endothelial growth factor. | 2007 May |
|
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 |
|
Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. | 2009 May 7 |
|
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 |
|
Comprehensive analysis of kinase inhibitor selectivity. | 2011 Oct 30 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17938863
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
Name | Type | Language | ||
---|---|---|---|---|
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Systematic Name | English |
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
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 | |||
|
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 | |||
|
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 | |||
|
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 | |||
|
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 | |||
|
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 | |||
|
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 | |||
|
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 |
ACTIVE MOIETY