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Details

Stereochemistry ACHIRAL
Molecular Formula C22H26N6O2
Molecular Weight 406.4808
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BMS-582949

SMILES

CCCNC(=O)C1=CN2N=CN=C(NC3=CC(=CC=C3C)C(=O)NC4CC4)C2=C1C

InChI

InChIKey=GDTQLZHHDRRBEB-UHFFFAOYSA-N
InChI=1S/C22H26N6O2/c1-4-9-23-22(30)17-11-28-19(14(17)3)20(24-12-25-28)27-18-10-15(6-5-13(18)2)21(29)26-16-7-8-16/h5-6,10-12,16H,4,7-9H2,1-3H3,(H,23,30)(H,26,29)(H,24,25,27)

HIDE SMILES / InChI
BMS-582949 acts as a dual action kinase inhibitor. It inhibits both p38 mitogen-activated protein kinase (p38 MAPK) activity and activation of p38. As a blocking agent for activation of p38 kinase BMS-582949 appeared to be well suited to resist such cellular responses that would drive p38 activation more strongly. BMS-582949 is in Phase II clinical trials for the treatment of rheumatoid arthritis, psoriasis, and atherosclerosis.

Originator

Curator's Comment: # Bristol-Myers Squibb Research and Development

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
13.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
15.3 μM
5 mg/kg single, intravenous
dose: 5 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
BMS-582949 plasma
Mus musculus
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
75.5 μM × h
10 mg/kg single, oral
dose: 10 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
BMS-582949 plasma
Mus musculus
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.6 h
5 mg/kg single, intravenous
dose: 5 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
BMS-582949 plasma
Mus musculus
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
14%
5 mg/kg single, intravenous
dose: 5 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
BMS-582949 plasma
Mus musculus
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Overview

Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​

Drug as perpetrator​

Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
BMS-582949: crystalline form of a p38alpha inhibitor? WO2008079857.
2009 Aug
Discovery of 4-(5-(cyclopropylcarbamoyl)-2-methylphenylamino)-5-methyl-N-propylpyrrolo[1,2-f][1,2,4]triazine-6-carboxamide (BMS-582949), a clinical p38α MAP kinase inhibitor for the treatment of inflammatory diseases.
2010 Sep 23
The effect of BMS-582949, a P38 mitogen-activated protein kinase (P38 MAPK) inhibitor on arterial inflammation: a multicenter FDG-PET trial.
2015 Jun
Patents

Patents

Sample Use Guides

300 mg, once daily, 12 weeks
Route of Administration: Oral
BMS-582949 was found to inhibit p38 activation in cells, as measured by phosphorylation of p38. Furthermore, BMS-582949 treatment of cells in which p38 had been activated by LPS rapidly reversed p38 activation as shown by loss of phosphorylation of p38. BMS-582949 is therefore a dual action p38 kinase inhibitor, inhibiting both p38 kinase activity and p38 activation in cells. X-ray crystallography revealed that BMS-582949 binding to p38a results in a conformational change of the activation loop which is phosphorylated by upstream kinases, whereas SCIO-469 had little effect. BMS-582949 may therefore inhibit phosphorylation of p38 by upstream MKK by inducing a less accessible conformation of the activation loop.
Name Type Language
BMS-582949
Common Name English
PYRROLO(2,1-F)(1,2,4)TRIAZINE-6-CARBOXAMIDE, 4-((5-((CYCLOPROPYLAMINO)CARBONYL)-2-METHYLPHENYL)AMINO)-5-METHYL-N-PROPYL-
Systematic Name English
PS-540446
Code English
BMS 582949
Common Name English
Code System Code Type Description
ChEMBL
CHEMBL1230065
Created by admin on Fri Dec 15 18:14:25 GMT 2023 , Edited by admin on Fri Dec 15 18:14:25 GMT 2023
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CAS
623152-17-0
Created by admin on Fri Dec 15 18:14:25 GMT 2023 , Edited by admin on Fri Dec 15 18:14:25 GMT 2023
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SMS_ID
100000175606
Created by admin on Fri Dec 15 18:14:25 GMT 2023 , Edited by admin on Fri Dec 15 18:14:25 GMT 2023
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FDA UNII
CR743OME9E
Created by admin on Fri Dec 15 18:14:25 GMT 2023 , Edited by admin on Fri Dec 15 18:14:25 GMT 2023
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DRUG BANK
DB12696
Created by admin on Fri Dec 15 18:14:25 GMT 2023 , Edited by admin on Fri Dec 15 18:14:25 GMT 2023
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PUBCHEM
10409068
Created by admin on Fri Dec 15 18:14:25 GMT 2023 , Edited by admin on Fri Dec 15 18:14:25 GMT 2023
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EPA CompTox
DTXSID90211380
Created by admin on Fri Dec 15 18:14:25 GMT 2023 , Edited by admin on Fri Dec 15 18:14:25 GMT 2023
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