BMS-582949 hydrochloride

"目录号: HY-14305A

MAPK/ERK Pathway-

BMS-582949盐酸盐是一种新型的选择性p38α MAPK抑制剂, IC50值为13 nM。

p38 MAPK

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生物活性

Description

BMS-582949 hydrochloride is a novel highly selective p38α MAPK inhibitor, inhibits p38α with IC50 of 13 nM. IC50 value: 13 nM[1]Target: p38αin vitro: BMS-582949 does not significantly inhibit cytochrome P450 isozymes 1A2, 2C9, 2C19, and 2D6 with IC50values >40 μM. It is a weak inhibitor of CYP3A4, with an IC50 value ranging from 18 to 40 μM based in multiple tests. BMS-582949 displays >2000-fold selectivity for p38α over a diverse panel of 57 kinases that include serine kinases, nonreceptor tyrosine kinases, receptor tyrosine kinases, and the p38γ and δ isoforms. BMS-582949 is also 450-fold selective over Jnk2, a MAP kinase involved in inflammation, and 190-fold selective over Raf[1].BMS-582949 is a novel highly selective p38α MAPK inhibitor [2]. in vivo: The mouse clearance rate for BMS-582949 is 4.4 mL/min/kg. And, at an oral dose of 10 mg/kg, the mouse AUC0?8 h for BMS-582949 is 75.5 μM·h. BMS-582949 exhibited oral bioavailability values of 90% and 60% in mice and rats, respectively[1].

Clinical Trial

NCT00162292

Bristol-Myers Squibb

Rheumatoid Arthritis

November 2005

Phase 1

NCT00399906

Bristol-Myers Squibb

Psoriasis

August 2007

Phase 2

NCT00605735

Bristol-Myers Squibb

Rheumatoid Arthritis, NOS

March 2008

Phase 2

NCT00570752

Bristol-Myers Squibb

Vascular Diseases

December 2008

Phase 2

NCT00162292

Bristol-Myers Squibb

Rheumatoid Arthritis

November 2005

Phase 1

NCT00399906

Bristol-Myers Squibb

Psoriasis

August 2007

Phase 2

NCT00605735

Bristol-Myers Squibb

Rheumatoid Arthritis, NOS

March 2008

Phase 2

NCT00570752

Bristol-Myers Squibb

Vascular Diseases

December 2008

Phase 2

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References

[1].Liu C, et al. 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. J Med Chem. 2010 Sep 23

[2].Emami H,  et al. The effect of BMS-582949, a P38 mitogen-activated protein kinase (P38 MAPK) inhibitor on arterial inflammation: a multicenter FDG-PET trial. Atherosclerosis. 2015 Jun;240(2):490-6.