| Bioactivity | AMG-548 hydrochloride, 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 hydrochloride is also extremely potent in the inhibition of whole blood LPS stimulated TNFα (IC50=3 nM)[1]. AMG-548 hydrochloride inhibits Wnt signaling by directly inhibiting Casein kinase 1 isoforms δ and ε[2]. |
| Invitro | AMG-548 hydrochloride shows >1000 fold selective against p38γ (Ki=2600 nM) and p38δ (ki=4100 nM). AMG-548 hydrochloride has an modest selectivity against JNK2 (ki=39 nM) and JNK3 (ki=61 nM). AMG-548 hydrochloride 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 hydrochloride (10 μM) inhibits the hDvl2 shift[2]. |
| In Vivo | AMG-548 hydrochloride 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 hydrochloride |
| Formula | C29H28ClN5O |
| Molar Mass | 498.02 |
| Transport | Room temperature in continental US; may vary elsewhere. |
| Storage | Please store the product under the recommended conditions in the Certificate of Analysis. |
| 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. |