| Identification | Back Directory | [Name]
4(3H)-Pyrimidinone, 2-[[(2S)-2-amino-3-phenylpropyl]amino]-3-methyl-5-(2-naphthalenyl)-6-(4-pyridinyl)-, hydrochloride (1:2) | [CAS]
2518299-32-4 | [Synonyms]
4(3H)-Pyrimidinone, 2-[[(2S)-2-amino-3-phenylpropyl]amino]-3-methyl-5-(2-naphthalenyl)-6-(4-pyridinyl)-, hydrochloride (1:2) | [Molecular Formula]
C29H28ClN5O | [MOL File]
2518299-32-4.mol | [Molecular Weight]
498.03 |
| Hazard Information | Back Directory | [Uses]
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]. | [in vivo]
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]. | [IC 50]
p38α: 0.5 nM (Ki); p38β: 3.6 nM (Ki); p38δ: 2600 nM (Ki); p38γ: 4100 nM (Ki); dog p38α: 5.0 nM (Ki); JNK 1: 11480 nM (Ki); JNK 2: 39 nM (Ki); JNK 3: 61 nM (Ki); CK1 | [References]
[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. DOI:10.2174/092986705774462914
[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/?. Chem Biol. 2011 Apr 22;18(4):485-94. DOI:10.1016/j.chembiol.2011.01.015 |
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