AMG-548

AMG-548, an orally active and selective p38α inhibitor (K_i=0.5 nM), shows slightly selective over p38β (K_i=36 nM) and >1000 fold selective against p38γ and p38δ. AMG 548 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]. In Vitro: AMG-548 shows >1000 fold selective against p38γ (K_i=2600 nM) and p38δ (k_i=4100 nM). AMG-548 has an modest selectivity against JNK2 (k_i=39 nM) and JNK3 (k_i=61 nM). AMG-548 is also 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 (10 μM) inhibits the hDvl2 shift^[2].
In Vivo: AMG-548 has rat F of 62% and dog F of 47%. The t_1/2 is 4.6 hours in rats and 7.3 hours in dogs^[1].