2518299-32-4

AMG-548 dihydrochloride, an orally active and selective p38α inhibitor (Ki=0.5 nM), shows slightly selective over p38β (Ki=36 nM) and >1000 fold selective against p38γ and p38δ. AMG-548 dihydrochloride is also extremely potent in the inhibition of whole blood LPS stimulated TNFα (IC50=3 nM)[1]. AMG-548 dihydrochloride inhibits Wnt signaling by directly inhibiting Casein kinase 1 isoforms δ and ε[2].

p38α: 0.5 nM (Ki); p38β: 3.6 nM (Ki); p38δ: 2600 nM (Ki); p38γ: 4100 nM (Ki); dog p38α: 5.0 nM (Ki); JNK 1: 11480 nM (Ki); JNK 2: 39 nM (Ki); JNK 3: 61 nM (Ki); CK1

[1] Lee MR, et al. MAP kinase p38 inhibitors: clinical results and an intimate look at their interactions with p38alphaprotein. Curr Med Chem. 2005;12(25):2979-94. DOI:10.2174/092986705774462914
[2] Verkaar F, 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 Apr 22;18(4):485-94. DOI:10.1016/j.chembiol.2011.01.015