AMG-548 is 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 and is also extremely potent in the inhibition of whole blood LPS stimulated TNFα (IC50=3 nM)[1]. AMG-548 inhibits Wnt signaling by directly inhibiting Casein kinase 1 isoforms δ and ε[2].

p38α:0.5 nM （ki）, p38δ:2600 nM （ki）, p38γ:4100 nM （ki）, JNK1:11480 nM （ki）, JNK2:39 nM （ki）, p38α (dog):5.0 nM （ki）, p38β:3.6 nM （ki）, JNK3:61 nM （ki）, CK1:

AMG-548 (10 μM) inhibits the hDvl2 shift[2]. AMG-548 is extremely potent in the inhibition of whole blood LPS stimulated TNFa (IC50=3 nM) and IL1b (IC50=7 nM) as well as TNFa induced IL-8 (IC50=0.7 nM) and IL-1b induced IL-6 (IC5050=1.3 nM) in human whole blood[1]. AMG-548 shows >1000 fold selective against p38γ (Ki=2600 nM) and p38δ (ki=4100 nM). AMG-548 has an modest selectivity against JNK2 (ki=39 nM) and JNK3 (ki=61 nM).

The t1/2 is 4.6 hours in rats and 7.3 hours in dogs[1]. AMG-548 has rat F of 62% and dog F of 47%.