Uses
AMG 548 is a selective and efficacious p38 mitogen-activated protein (MAP) kinase inhibitor, which are a class of inhibitors that are investigated towards treating inflammatory diseases.
Biological Activity
amg 548 is a potent and selective inhibitor of p38α with ic50 values of 0.5, 3.6, 2600 and 4100 nm for p38α, p38β, p38γ and p38δ, respectively.p38 mitogen-activated protein kinase (p38) is a serine/threonine kinase and is responsive to a variety of cellular stresses including inflammatory cytokines, osmotic shock, ultraviolet light, lipopolysaccharides (lps) and growth factors. p38α kinase involved in the biosynthesis of tnfα and il-1β at the transcriptional and translational level [1][2].amg 548 is a potent and selective p38α inhibitor. in the antagonistic enzyme fragment complementation (efc) and β-catenin-driven luciferase (supertopflash) reporter gene assays, amg 548 inhibited wnt/β-catenin signaling, which was due to cross-reactivity with another kinase. amg 548 inhibited 17 kinases by more than 80%. in u2os-efc cells, amg 548 inhibited ckiδ and ckiε, which played an important role in the activation of wnt/b-catenin signaling. also, the concentration of amg 548 needed to inhibit ckiδ/ε in cells was closely approximate that required to inhibit wnt/b-catenin signaling in the efc and topflash assays, which suggested amg 548 inhibited wnt/b-catenin signaling mediated by the inhibition of ckiδ/ε [3].
References
[1]. dominguez c, powers da, tamayo n. p38 map kinase inhibitors: many are made, but few are chosen. curr opin drug discov devel, 2005, 8(4): 421-430.
[2]. lee mr, dominguez c. map kinase p38 inhibitors: clinical results and an intimate look at their interactions with p38alpha protein. curr med chem, 2005, 12(25): 2979-2994.
[3]. verkaar f, van der doelen aa, smits jf, et al. inhibition of wnt/β-catenin signaling by p38 map kinase inhibitors is explained by cross-reactivity with casein kinase iδ/?. chem biol, 2011, 18(4): 485-494.
