AMG-548 dihydrochloride 

AMG-548 dihydrochloride, 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 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].

AMG-548 dihydrochloride shows >1000 fold selective against p38γ (K_i=2600 nM) and p38δ (k_i=4100 nM). AMG-548 dihydrochloride has an modest selectivity against JNK2 (k_i=39 nM) and JNK3 (k_i=61 nM). AMG-548 dihydrochloride 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 dihydrochloride (10 μM) inhibits the hDvl2 shift^[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

AMG-548 dihydrochloride 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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

534.48

Solid

C₂₉H₂₉Cl₂N₅O

O=C1N(C)C(NCC(N)CC2=CC=CC=C2)=NC(C3=CC=NC=C3)=C1C4=CC=C5C=CC=CC5=C4.Cl.Cl

Room temperature in continental US; may vary elsewhere.

-20°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

• [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.  [Content Brief]

  [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/ɛ. Chem Biol. 2011 Apr 22;18(4):485-94.  [Content Brief]