AMG-548 hydrochloride是一种口服有效的，选择性p38α抑制剂 (Ki=0.5 nM)，对p38β略有选择性 (Ki=36 nM) 并且对 p38γ 和 p38δ 具有 >1000 倍的选择性。AMG 548 hydrochloride也有效抑制全血 LPS 刺激的TNFα(IC50=3 nM)。AMG-548 hydrochloride通过直接抑制酪蛋白激酶 1 (Casein Kinase 1) 同种型 δ 和 ε 来抑制 Wnt 信号传导。

AMG-548 hydrochloride, an orally active and selective p38α inhibitor ( K i =0.5 nM), shows slightly selective over p38β ( K i =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 ( IC 50 =3 nM) [1]. AMG-548 hydrochloride inhibits Wnt signaling by directly inhibiting Casein kinase 1 isoforms δ and ε [2].

AMG-548 hydrochloride shows >1000 fold selective against p38γ (K i =2600 nM) and p38δ (k i =4100 nM). AMG-548 hydrochloride has an modest selectivity against JNK2 (k i =39 nM) and JNK3 (k i =61 nM). AMG-548 hydrochloride is also extremely potent in the inhibition of whole blood LPS stimulated TNFa (IC 50 =3 nM) and IL1b (IC 50 =7 nM) as well as TNFa induced IL-8 (IC 50 =0.7 nM) and IL-1b induced IL-6 (IC50 50 =1.3 nM) in human whole blood [1]. AMG-548 hydrochloride (10 μM) inhibits the hDvl2 shift [2].

AMG-548 hydrochloride 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 [1].

C29H28ClN5O

498.02

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years