PH-797804

製品コードS2726 バッチS272602

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₂H₁₉BrF₂N₂O₃
	分子量	477.3	CAS No.	586379-66-0
Solubility (25°C)*	体外	DMSO	96 mg/mL (201.13 mM)
		Ethanol	20 mg/mL (41.9 mM)
		Water	Insoluble
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	PH-797804 is a novel pyridinone inhibitor of p38α with IC50 of 26 nM in a cell-free assay; 4-fold more selective versus p38β and does not inhibit JNK2. Phase 2.
in 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. 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	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]

プロトコル(参考用のみ)

キナーゼアッセイ	P38 kinase assay
キナーゼアッセイ	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	細胞株	Rheumatoid arthritis synovial fibroblast(s)
	濃度	--
	反応時間	--
	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	動物モデル	LPS-induced chronic inflammation rat model
	投薬量	0.001-1 mg/kg
	投与方法	Oral gavage 4 hours before LPS administration

参考

カスタマーフィードバック

: Data independently produced by , , Dr.Wang from Southern Medical Hospital

: ,

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Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

SARS-CoV-2 spike protein-ACE2 interaction increases carbohydrate sulfotransferases and reduces N-acetylgalactosamine-4-sulfatase by p38 MAPK [ Signal Transduct Target Ther, 2024, 9(1):39]	PubMed: 38355690
Mitocurcumin utilizes oxidative stress to upregulate JNK/p38 signaling and overcomes Cytarabine resistance in acute myeloid leukemia [ Cell Signal, 2024, 114:111004]	PubMed: 38048856
Coadaptation fostered by the SLIT2-ROBO1 axis facilitates liver metastasis of pancreatic ductal adenocarcinoma [ Nat Commun, 2023, 14(1):861]	PubMed: 36792623
HUWE1 controls tristetraprolin proteasomal degradation by regulating its phosphorylation [ Elife, 2023, 12e83159]	PubMed: 36961408
HUWE1 controls tristetraprolin proteasomal degradation by regulating its phosphorylation [ Cell Biology, 2023, 10.7554/eLife.83159]	PubMed: None
Synthesis and Biological Activity of a VHL-Based PROTAC Specific for p38α [ Cancers (Basel), 2023, 15(3)611]	PubMed: 36765568
Integrative analysis of drug response and clinical outcome in acute myeloid leukemia [ Cancer Cell, 2022, S1535-6108(22)00312-9]	PubMed: 35868306
Distinct histopathological phenotypes of severe alcoholic hepatitis suggest different mechanisms driving liver injury and failure [ J Clin Invest, 2022, 132(14)e157780]	PubMed: 35838051
P38α MAPK is a gatekeeper of uterine progesterone responsiveness at peri-implantation via Ube3c-mediated PGR degradation [ Proc Natl Acad Sci U S A, 2022, 119(32):e2206000119]	PubMed: 35914132
Hyperphosphorylated tau mediates neuronal death by inducing necroptosis and inflammation in Alzheimer's disease [ J Neuroinflammation, 2022, 19(1):205]	PubMed: 35971179

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人間や獣医の診断であるか治療的な使用のためにでない。

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