| Bioactivity | AMG-548, 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 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]. | |||||||||
| Invitro | 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). 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 t1/2 is 4.6 hours in rats and 7.3 hours in dogs[1]. | |||||||||
| Name | AMG-548 | |||||||||
| CAS | 864249-60-5 | |||||||||
| Formula | C29H27N5O | |||||||||
| Molar Mass | 461.56 | |||||||||
| Appearance | Solid | |||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | |||||||||
| Storage |
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| Reference | [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. [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. |