BMS-582949

Investigational

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 Search

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19505194 | https://www.ncbi.nlm.nih.gov/pubmed/20804198

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

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
MAP kinase p38 alpha 35 Target ID: CHEMBL260 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20804198	Inhibitor 8297		13.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Rheumatoid arthritis 316 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19505194	Primary		Phase II 1132	Unknown Approved Use Unknown
Psoriasis 84 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19505194	Primary		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
15.3 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20804198	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

Value	Dose	Co-administered	Analyte	Population
75.5 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20804198	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20804198	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
14% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20804198	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

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2C19 1478

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20804198/	likely [IC50 >40 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20804198/	likely [IC50 >40 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20804198/	likely [IC50 >40 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20804198/	likely [IC50 >40 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20804198/	weak [IC50 18 uM]

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/20804198/

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00EJGL	https://www.1pchem.com/search?query=1P00EJGL
1PlusChem LLC	1P00GURD	https://www.1pchem.com/search?query=1P00GURD
AChemBlock	O32836	http://www.achemblock.com/catalogsearch/result/?q=O32836
ApexBio Technology	B6187	https://www.apexbt.com/catalogsearch/result/?q=B6187
ApexBio Technology	B7850	https://www.apexbt.com/catalogsearch/result/?q=B7850
AstaTech	44151	http://astatechinc.com/CPSResult.php?CRNO=44151
Axon MedChem	2856	https://www.axonmedchem.com/product/2856
BLD Pharm	BD630997	http://www.bldpharm.com/search/Search.html?keyword=BD630997
BLD Pharm	BD689149	http://www.bldpharm.com/search/Search.html?keyword=BD689149
Chem Scene	CS-5621	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-5621
ChemShuttle	152163	https://www.chemshuttle.com/catalogsearch/result/?q=152163
Excenen	EX-A1265	http://www.excenen.com/searchresultlist.php?id=EX-A1265
KeyOrganics	AS-35330	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-35330
MedChem Express	HY-14305A	https://www.medchemexpress.com/search.html?q=HY-14305A&ft=&fa=&fp=
MolPort	MolPort-044-560-326	https://www.molport.com/shop/molecule-link/MolPort-044-560-326
MolPort	MolPort-044-567-613	https://www.molport.com/shop/molecule-link/MolPort-044-567-613
Molnova	M17555	https://www.molnova.com/en/serch-list.html?keywords=M17555
Molnova	M17654	https://www.molnova.com/en/serch-list.html?keywords=M17654
MuseChem	I004531	https://www.musechem.com/product/I004531.html
MuseChem	M019910	https://www.musechem.com/product/M019910.html
Selleck Chemicals	S8124	http://www.selleckchem.com/search.html?searchDTO.searchParam=S8124
ShangHai Biochempartner	BCP14356	http://www.biochempartner.com/search_BCP14356
ShangHai Biochempartner	BCP17651	http://www.biochempartner.com/search_BCP17651
TargetMol	T3462	https://www.targetmol.com/search?keyword=T3462
TargetMol	T6789	https://www.targetmol.com/search?keyword=T6789
eMolecules	303200575	https://orderbb.emolecules.com/search/#?query=303200575
eMolecules	84836389	https://orderbb.emolecules.com/search/#?query=84836389
eMolecules	95536284	https://orderbb.emolecules.com/search/#?query=95536284
mcule	MCULE-4210521566	https://mcule.com/MCULE-4210521566/
mcule	MCULE-6708639941	https://mcule.com/MCULE-6708639941/

PubMed

Title	Date	PubMed
BMS-582949: crystalline form of a p38alpha inhibitor? WO2008079857.	2009 Aug	19505194
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	20804198
The effect of BMS-582949, a P38 mitogen-activated protein kinase (P38 MAPK) inhibitor on arterial inflammation: a multicenter FDG-PET trial.	2015 Jun	25913664

Patents

Sample Use Guides

In Vivo Use Guide

300 mg, once daily, 12 weeks

Route of Administration: Oral

In Vitro Use Guide

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