AMG-548 is a selective and orally active p38α MAPK inhibitor (Ki = 0.5 nM), with higher selectivity than p38β, p38γ, and p38δ, and can also inhibit the TNFα, CK1δ/ε, and Wnt signalling pathways.

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

Methods: U2OS-EFC cells were treated with AMG-548 (0.01-0.1 μM) to investigate its ability to mediate Wnt-3a-induced hDvl2 mobility shift.
Results: AMG-548 inhibited hDvl2 displacement at micromolar concentrations. [2]

Experimental data showed that AMG-548 exhibited differentiated pharmacokinetic characteristics in different animal models: the elimination half-life (t1/2) in rats was 4.6 hours, while in canine models it was extended to 7.3 hours. In terms of bioavailability (F value), the compound reached 62% in rats, while it was relatively low at 47% in dogs. These Results indicate that AMG-548 has significant species differences, and its metabolic clearance rate and absorption efficiency vary significantly between different animal models. [1]