BMS-582949 hydrochloride |
| Catalog No.GC10593 |
Le chlorhydrate de BMS-582949 est un inhibiteur de p38α MAPK actif par voie orale et hautement sélectif, avec une IC50 de 13 nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 912806-16-7
Sample solution is provided at 25 µL, 10mM.
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BMS-582949 hydrochloride is a novel, potent and highly selective p38α mitogen-activated protein kinase (p38α MAPK) inhibitor [1].
The p38α MAP kinase plays a critical role in regulating the production of many inflammatory cytokines, including TNF-α and IL-1β. Excessive production of TNF-α and IL-1β has been implicated in many inflammatory diseases [1].
BMS-582949 hydrochloride potently inhibited the activity of p38α MAPK with the IC50 value of 13 nM [1]. BMS-582949 showed no significant effects on cytochrome P450 isozymes 1A2, 2C9, 2C19, and 2D6 with the IC50 values of >40 μM. BMS-582949 weakly inhibited the activity of CYP3A4, with the IC50 value of 18-40 μM. BMS-582949 displayed >2000-fold selectivity for p38α over a diverse panel of 57 kinases, include serine kinases, receptor tyrosine kinases, nonreceptor tyrosine kinases, and the p38γ and δ isoforms. BMS-582949 showed 450-fold selectivity over Jnk2, a MAP kinase involved in inflammation, and 190-fold selective over Raf [1]. In mice, after oral administration of BMS-582949 (10 mg/kg), the clearance rate for BMS-582949 is 4.4 mL/min/kg. BMS-582949 exhibited oral bioavailability values of 90% and 60% in mice and rats, respectively [1].
BMS-582949 is currently under Phase II clinical trials for the treatment of inflammatory diseases. In stable atherosclerosis, treatment with BMS-582949 for 12 weeks did not reduce arterial inflammation or hs-CRP compared to placebo whereas intensification of statin therapy significantly decreased arterial inflammation [2].
References:
[1] Liu C, Lin J, Wrobleski S T, 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]. Journal of medicinal chemistry, 2010, 53(18): 6629-6639.
[2] Emami H, Vucic E, Subramanian S, et al. The effect of BMS-582949, a P38 mitogen-activated protein kinase (P38 MAPK) inhibitor on arterial inflammation: a multicenter FDG-PET trial[J]. Atherosclerosis, 2015, 240(2): 490-496.
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