Size | Price | Stock | Qty |
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1mg |
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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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1g |
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Other Sizes |
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Purity: ≥98%
Targets |
p38α (IC50 = 26 nM); p38α (Ki = 5.8 nM); p38β (Ki = 40 nM)
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ln Vitro |
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. At concentrations up to 1 μM, PH-797804 has no inhibitory impact on the JNK pathway (c-Jun phosphorylation) or ERK pathway (ERK phosphorylation) in U937 cells. With an IC50 of 3 nM in primary rat bone marrow cells, PH-797804 inhibits RANKL- and M-CSF-induced osteoclast formation in a concentration-dependent manner.[1] The activity of PH-797804 is specific because the IC50 values for it against the following targets have been found to be higher than 200 μM (unless otherwise noted): CDK2, ERK2, IKK1, IKK2, IKKi, MAPKAP2, MAPKAP3, MKK7 (>100 μM), MNK, MSK (>164 μM), PRAK, RSK2, and TBK1.[2]
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ln Vivo |
In both rats and cynomolgus monkeys, oral administration of PH-797804 effectively reduces the acute inflammatory reactions brought on by systemically administered endotoxin. In chronic disease models, PH-797804 treatment for 10 days shows strong anti-inflammatory activity, significantly lowering joint inflammation and related bone loss in rats with streptococcal cell wall-induced arthritis and mice with collagen-induced arthritis. In rats and cynomolgus monkeys, the ED50 values were 0.07 mg/kg and 0.095 mg/kg, respectively, according to dose-response analysis. In a human endotoxin challenge model, PH-797804 inhibits LPS-induced TNF-α, IL-6, and MK-2 activity in a dose- and concentration-dependent manner.[1]
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Enzyme Assay |
The phosphorylation of GST-c-Jun or the epidermal growth factor receptor peptide (EGFRP) by p38 kinases is assessed using a resin capture assay method. 25 mM HEPES, pH 7.5, 10 mM magnesium acetate, 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 p38 kinase reactions are included in reaction mixtures. To begin the reaction, 25 nM p38α kinase is added, resulting in a final volume of 50 μl. For 30 minutes, the p38α kinase reactions are incubated at 25 °C. Under these circumstances, both p38 kinase's product formation is time-dependently linear. The addition of 150 μl of AG 1 × 8 ion exchange resin in 900 mM sodium formate, pH 3.0, stops the reaction and removes the unreacted [γ-33P]ATP. Solutions are thoroughly combined and then left to stand for 5 minutes. The phosphorylated substrate is extracted from the mixture in a 50-μl aliquot, which is then transferred to a 96-well plate. A TopCount NXT microplate scintillation and luminescence counter is used to add 150 μL of the MicroScint-40 scintillation cocktail to each well and measure the radioactivity levels.
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Cell Assay |
The 3-(4,5-dimethylthiazol-2-yl)-) diphenyl tetrazolium bromide assay is used to measure cell viability. With a reference wavelength of 630 nm and a test wavelength of 570 nm, absorbance is measured on an ELISA plate reader.
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Animal Protocol |
LPS-induced chronic inflammation rat model
0.001-1 mg/kg Oral gavage 4 hours before LPS administration |
References |
Molecular Formula |
C22H19BRF2N2O3
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Molecular Weight |
477.3
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Exact Mass |
477.300
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Elemental Analysis |
C, 55.36; H, 4.01; Br, 16.74; F, 7.96; N, 5.87; O, 10.06
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CAS # |
586379-66-0
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Related CAS # |
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Appearance |
Solid powder
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SMILES |
CC1=C(C=C(C=C1)C(=O)NC)N2C(=CC(=C(C2=O)Br)OCC3=C(C=C(C=C3)F)F)C
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InChi Key |
KCAJXIDMCNPGHZ-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C22H19BrF2N2O3/c1-12-4-5-14(21(28)26-3)9-18(12)27-13(2)8-19(20(23)22(27)29)30-11-15-6-7-16(24)10-17(15)25/h4-10H,11H2,1-3H3,(H,26,28)
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Chemical Name |
3-[3-bromo-4-[(2,4-difluorophenyl)methoxy]-6-methyl-2-oxopyridin-1-yl]-N,4-dimethylbenzamide
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Synonyms |
PH 797804; PH797804; PH-797804
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3 mg/mL (6.29 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.24 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: 2% DMSO+30% PEG 300+5% Tween 80+ddH2O: 5mg/mL |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.0951 mL | 10.4756 mL | 20.9512 mL | |
5 mM | 0.4190 mL | 2.0951 mL | 4.1902 mL | |
10 mM | 0.2095 mL | 1.0476 mL | 2.0951 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT00383188 | Completed | Drug: placebo Drug: PH-797804 |
Arthritis, Rheumatoid | Pfizer | December 15, 2006 | Phase 2 |
NCT01102660 | Completed | Drug: PH-797804 Drug: Placebo |
Osteoarthritis | Pfizer | May 2010 | Phase 2 |
NCT01479647 | Completed | Drug: PH-797804 | Healthy Volunteers | Pfizer | December 2011 | Phase 1 |
NCT01217918 | Completed | Drug: 1 mg Drug: 5 mg |
Healthy | Pfizer | October 2010 | Phase 1 |
NCT02084485 | Completed | Drug: PH-797804 Drug: Placebo |
Healthy | Pfizer | September 2006 | Phase 1 |