PH-797804 是一种 ATP 竞争性的，选择性的p38α/p38β抑制剂，对 p38α 的IC50为 26 nM，Ki值为 5.8 nM，对 p38β 的Ki值为 40 nM。

PH-797804 is a pyridinone inhibitor of p38α (IC50: 26 nM, in a cell-free assay); 4-fold more selective versus p38β and does not inhibit JNK2.

PH-797804抗炎活性较强,治疗链球菌细胞壁诱导的关节炎及大小鼠胶原诱导的关节炎时,处理10天可使关节发炎和相关的骨质流失显著降低.在人类Endotoxin 挑战模型中,PH-797804剂量和浓度依赖性地抑制脂多糖诱导的 IL-6,TNF-α和MK-2活性.Endotoxin全身给药大鼠和食蟹猴可造成急性炎症反应,口服PH-797804可有效抑制该反应（ED50：0.07和0.095 mg/kg）.

PH-797804对下述靶点的IC50高于200 μM: CDK2,ERK2,IKK1/2,IKKi,MAPKAP2/3,MKK7 (>100 μM),MNK,MSK (>164 μM),PRAK,RSK2和 TBK1。在人类单核U937细胞系中,PH-797804对脂多糖诱导的TNF-α产生和p38 激酶活性起阻断作用（IC50：5.9/1.1 nM）。作用于U937 细胞时,PH-797804（1 μM）没有抑制JNK 通路(c-Jun 磷酸化)或ERK 通路(ERK 磷酸化)。在原代大鼠骨髓细胞中,PH-797804浓度依赖性地抑制RANKL-和M-CSF诱导的破骨细胞形成（IC50：3 nM）。

P38 kinase assay: A resin capture assay method is used to determine the phosphorylation of epidermal growth factor receptor peptide (EGFRP) or GST-c-Jun by p38 kinases. Reactions mixtures contain 25 mM HEPES, pH 7.5, 10 mM magnesium acetate, ATP (at the indicated concentration), 0.05 to 0.3 μCi of [γ-33P]ATP, 0.8 mM dithiothreitol, and either 200 μM EGFRP or 10 μM GST-c-Jun for p38α kinase reactions. The reaction is initiated by the addition of 25 nM p38α kinase to give a final volume of 50 μl. The p38αkinase reactions are incubated at 25 °C for 30 minutes. Under these conditions, the formation of product for both p38αkinase is linear with time. The reaction is stopped, and the unreacted [γ-33P]ATP is removed by the addition of 150 μl of AG 1 × 8 ion exchange resin in 900 mM sodium formate, pH 3.0. Once thoroughly mixed, solutions are allowed to stand for 5 minutes. A 50-μl aliquot of head volume containing the phosphorylated substrate is removed from the mixture and transferred to a 96-well plate. MicroScint-40 scintillation cocktail (150 μL) is added to each well and the radioactivity quantities using a TopCount NXT microplate scintillation and luminescence counter.

586379-66-0

C22H19BrF2N2O3

477.306

PH797804

DMSO:89 mg/mL (186.5 mM)
H2O:<1 mgml
Ethanol:7 mg/mL (14.66 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years