For research use only. Not for therapeutic Use.
AMG-548 dihydrochloride, 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 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 (Ki=2600 nM) and p38δ (ki=4100 nM). AMG-548 dihydrochloride has an modest selectivity against JNK2 (ki=39 nM) and JNK3 (ki=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].
AMG-548 dihydrochloride 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].
| Catalog Number | I046086 |
| CAS Number | 2518299-32-4 |
| Synonyms | 2-[[(2S)-2-amino-3-phenylpropyl]amino]-3-methyl-5-naphthalen-2-yl-6-pyridin-4-ylpyrimidin-4-one;dihydrochloride |
| Molecular Formula | C29H29Cl2N5O |
| Purity | ≥95% |
| InChI | InChI=1S/C29H27N5O.2ClH/c1-34-28(35)26(24-12-11-21-9-5-6-10-23(21)18-24)27(22-13-15-31-16-14-22)33-29(34)32-19-25(30)17-20-7-3-2-4-8-20;;/h2-16,18,25H,17,19,30H2,1H3,(H,32,33);2*1H/t25-;;/m0../s1 |
| InChIKey | WQZUYJOJJJERDI-WLOLSGMKSA-N |
| SMILES | CN1C(=O)C(=C(N=C1NCC(CC2=CC=CC=C2)N)C3=CC=NC=C3)C4=CC5=CC=CC=C5C=C4.Cl.Cl |
| 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. |
