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AMG-548 dihydrochloride

產(chǎn)品活性：AMG-548 dihydrochloride 是一種口服有效的，選擇性 p38α 抑制劑 (K_i=0.5 nM)，對 p38β 略有選擇性 (K_i=36 nM) 并且對 p38γ 和 p38δ 具有 >1000 倍的選擇性。AMG-548 dihydrochloride 也有效抑制全血 LPS 刺激的 TNFα (IC₅₀=3 nM)。AMG-548 dihydrochloride 通過直接抑制酪蛋白激酶 1 (Casein kinase 1) 同種型 δ 和 ε 來抑制 Wnt 信號傳導。

研究領域：MAPK/ERK Pathway  |  Stem Cell/Wnt  |  Cell Cycle/DNA Damage

作用靶點：p38 MAPK  |  Casein Kinase

In Vitro: 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.
AMG-548 dihydrochloride (10 μM) inhibits the hDvl2 shift.

In Vivo: 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.

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