Biological Activity
bms-582949 is a p38 mapk inhibitorp38r map kinase plays a key role in regulating the biosynthesis of various inflammatory cytokines, such as tumor necrosis factor alpha and interleukin-1β. thus, p38r inhibitors are considered as a promising therapy for inflammatory disease treatment.
in vitro
bms-582949 was found to be 450-fold selective over jnk2, a map kinase involved in inflammation, and 190-fold selective against raf. moreover, the binding mode of bms-582949 with p38r was further demonstrated by x-ray crystallographic analyses [1].
in vivo
in a pseudoestablished rat adjuvant arthritis model, bms-582949 at doses of 10 and 100 mg/kg was found to display dose-dependent reduction in paw swelling with qd dosing. in addition, with bid dosing at doses of 1 and 5 mg/kg, bms-582949 showed improved efficacy, resulting in great reduction in paw swelling. moreover, the statistically significant reduction in paw swelling was also observed with the treatment of bms-582949 at doses as low as 0.3 mg/kg bid [1].
target
| Target | Value |
p38 MAPK
(Cell-free assay) | < td style="border-bottom: 1px dotted #ccc;padding: 5px;"> 13 nM
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;53(18):6629-39.
[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.
