PH-797804 化学構造
分子量: 477.3



Quality Control & MSDS


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製品説明 pH-797804は、26nMのIC50によるp38αへの新しいピリジンケトン阻害剤です。
ターゲット p38α
IC50 26 nM [1]
In vitro試験 PH-797804 blocks LPS-induced TNF-α production and p38 kinase activity in the human monocytic U937 cell line, with comparable IC50 of 5.9 nM and 1.1 nM. PH-797804 has no inhibitory effect on either the JNK pathway (c-Jun phosphorylation) or ERK pathway (ERK phosphorylation) in U937 cells at concentrations up to 1 μM. PH-797804 inhibits RANKL- and M-CSF-induced osteoclast formation in a concentration-dependent manner, with IC50 of 3 nM in primary rat bone marrow cells. [1] IC50 values for PH-797804 against the following targets have been determined to be greater than 200 μM (unless specified): CDK2, ERK2, IKK1, IKK2, IKKi, MAPKAP2, MAPKAP3, MKK7 (>100 μM), MNK, MSK (>164 μM), PRAK, RSK2, and TBK1, which means the activity of PH-797804 is specific. [2]
In vivo試験 Orally dosing of PH-797804 effectively inhibits acute inflammatory responses induced by systemically administered endotoxin in both rat and cynomolgus monkeys. PH-797804 treatment for 10 days demonstrates robust anti-inflammatory activity in chronic disease models, significantly reducing both joint inflammation and associated bone loss in streptococcal cell wall-induced arthritis in rats and mouse collagen-induced arthritis. Dose-response analysis resulted in ED50 values of 0.07 mg/kg and 0.095 mg/kg in rat and cynomolgus monkeys, respectively. PH-797804 inhibits LPS-induced TNF-α, IL-6, and MK-2 activity in a dose- and concentration-dependent manner in a human endotoxin challenge model. [1]
臨床試験 PH-797804 is now under the Phase II clinical trial to evaluate the efficacy and safety for 12 weeks in adults with moderate to severe chronic obstructive pulmonary disease (COPD).

プロトコル (参考用のみ)

キナーゼアッセイ: [1]

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.

細胞アッセイ: [1]

細胞株 Rheumatoid arthritis synovial fibroblast(s)
実験の流れ Cell viability is evaluated using the 3-(4,5-dimethylthiazol-2-yl)-) diphenyl tetrazolium bromide assay. Absorbance is measured on an ELISA plate reader with a test wavelength of 570 nm and a reference of 630 nm.

動物実験: [1]

動物モデル LPS-induced chronic inflammation rat model
製剤 PH-797804 is prepared as a suspension in a vehicle consisting of 0.5% methylcellulose and 0.025% Tween 20.
投薬量 0.001-1 mg/kg
投与方法 Oral gavage 4 hours before LPS administration

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)
Body Surface Area (m2)0.0070.0250.
Km factor361285201220
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)



Download PH-797804 SDF
分子量 477.3


CAS No. 586379-66-0
保管 2年-20℃
6月-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMSO 96 mg/mL (201.13 mM)
エタノール 7 mg/mL (14.66 mM)
<1 mg/mL (<1 mM)
In vivo 2% DMSO+30% PEG 300+5% Tween 80+ddH2O 5mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
化学名 3-(4-(2,4-difluorobenzyloxy)-3-bromo-6-methyl-2-oxopyridin-1(2H)-yl)-N,4-dimethylbenzamide

カスタマーフィードバック (4)

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Source Dr.Wang from Southern Medical Hospital . PH-797804 purchased from Selleck
Method Western blot
Cell Lines A549 cells
Concentrations 0-10 uM
Incubation Time 2 h
Results Effect of MEK inhibitor PH-797804 in A549 cells. A549 cells were incubated with increasing concentrations of PH-797804 for 2 h. The cell lysates were harvested and phosphorylation of indicated proteins was determined by Western blotting.

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Source PH-797804 purchased from Selleck
Method ELISA
Cell Lines Human peripheral blood mononuclear or U937 cells
Incubation Time 1 h
Results Human peripheral blood mononuclear cells (PBMC) or U937 cells (PMA-differentiated into macrophages) were pre-treated with PH-797804 for 1 hr before stimulating with 100 ng/ml LPS overnight. TNF-a was measured in the culture supernatant by ELISA. Calculated EC50s were 3.4 nM and 5.2 nM for PBMC and U937 macrophages, respectively.

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Source PH-797804 purchased from Selleck
Method ELISA
Cell Lines CD-1 mice
Concentrations 1 mg/kg
Incubation Time 0-8 h
Results CD-1 mice (n=3) were oral gavaged with vehicle or PH-797804 at t = -0.5 hr. At t = 0 hr, mice were challenged with 10 mg/kg LPS i.p. injection. Plasma at indicated time points were evaluated for TNF-a by ELISA.

Click to enlarge
Source PH-797804 purchased from Selleck
Method Western blot
Cell Lines HEK293 cells
Concentrations 10 -1000 nM
Incubation Time 1 h
Results PH797804 treatment resulted in a reduction of p38 phosphorylation in HEK293 cells.

文献中の引用 (4)



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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID