PH-797804

Name: PH-797804
Brand: Selleck Chemicals
SKU: S2726
Rating: 5 (19 reviews)

For research use only. Not for use in humans.

Catalog No.S2726

19 publications

Molecular Weight(MW): 477.3

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.

Selleck's PH-797804 has been cited by 19 publications

Cell Metab, 2019, 29(1):141-155

PubMed: 30174305 ( click the link to review the publication )

Nat Med, 2018, 24(3):271-281

PubMed: 29400712 ( click the link to review the publication )

Cancer Cell, 2018, 33(6):1094-1110

PubMed: 29805078 ( click the link to review the publication )

Nat Commun, 2019, 10(1):448

PubMed: 30683885 ( click the link to review the publication )

Nat Commun, 2019, 10(1):3071

PubMed: 31296856 ( click the link to review the publication )

Oncogene, 2019, 38(49):7433-7446

PubMed: 31427736 ( click the link to review the publication )

Cell Death Dis, 2019, 10(6):376

PubMed: 31092814 ( click the link to review the publication )

Nanomedicine (Lond), 2019, 14(18):2409-2422

PubMed: 31456488 ( click the link to review the publication )

Invest Ophthalmol Vis Sci, 2018, 59(10):4218-4227

PubMed: 30128493 ( click the link to review the publication )

Biochemistry, 2018, 57(48):6715-6725

PubMed: 30418016 ( click the link to review the publication )

Nat Cell Biol, 2017, 19(8):996-1002

PubMed: 28752853 ( click the link to review the publication )

Nat Chem Biol, 2017, 13(1):38-45

PubMed: 27820799 ( click the link to review the publication )

Pharmacol Res, 2016, 113(Pt A):216-227

PubMed: 27543462 ( click the link to review the publication )

J Oral Pathol Med, 2016, 45(8):605-12

PubMed: 26775638 ( click the link to review the publication )

J Biol Chem, 2015, 290(17):10791-803

PubMed: 25752609 ( click the link to review the publication )

Oncotarget, 2015, 6(11):8539-51

PubMed: 25890501 ( click the link to review the publication )

Nat Cell Biol, 2014, 16(7):685-94

PubMed: 24880666 ( click the link to review the publication )

EMBO Mol Med, 2014, 5(11):1759-74

PubMed: 24115572 ( click the link to review the publication )

Oncotarget, 2014, 5(10):3145-58

PubMed: 24762669 ( click the link to review the publication )

Purity & Quality Control

Choose Selective p38 MAPK Inhibitors

Biological Activity

Description

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.

Targets

p38α ^[1] (Cell-free assay)	p38β ^[1] (Cell-free assay)
26 nM	102 nM

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]

Cell Data

Cell Lines	Assay Type	Activity Description	PMID
human U937 cells	NH\HfVVHfW6ldHnvckBie3OjeR?=	M33kUGlvcGmkaYTpc44hd2ZicEO4ZYxxcGFia3nuZZNmNWSncHXu[IVvfCCKU2CtNlcheGixc4Doc5J6dGG2aX;uJIlvKGi3bXHuJHU6OzdiY3XscJMtKEmFNUC9NE4xODFyNTFOwG0>	MVGyNVYzODZ7OR?=
human monocytes	NFv2O2lHfW6ldHnvckBie3OjeR?=	NH[0S\|RCdnSraX7mcIFudWG2b4L5JIFkfGm4aYT5JIlvKGi3bXHuJI1wdm:leYTld{Bie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJGxRWy2rbnT1Z4VlKFSQRnHsdIhiKHC{b3T1Z5Rqd25uIFnDOVA:OC5yMEO0JO69VQ>?	NXLDb3JOOjF4MkC2PVk>
human PBMC	NHrrTYVHfW6ldHnvckBie3OjeR?=	M1j1OGFvfGmrbn\sZY1u[XSxcomgZYN1cX[rdImgbY4hcHWvYX6gVGJOSyCjc4Pld5Nm\CCjczDpcohq[mm2aX;uJI9nKEySUz3pcoR2[2WmIGTOSoFteGijIILlcIVie2VicILleJJm[XSnZDDmc5IhOSCqcjDi[YZwemViTGDTJJRz\WG2bXXueEBu\WG\|dYLl[EBi\nSncjCxPEBpenNuIFnDOVA:OC5yMUWg{txO	MkXaNlE3PDF{MUG=

... Click to View More Cell Line Experimental Data

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]

Protocol

Kinase Assay: ^[1]	- Collapse 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.
Cell Research: ^[1]	- Collapse Cell lines: Rheumatoid arthritis synovial fibroblast(s) Concentrations: -- Incubation Time: -- Method: 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. (Only for Reference)
Animal Research: ^[1]	- Collapse Animal Models: LPS-induced chronic inflammation rat model Formulation: PH-797804 is prepared as a suspension in a vehicle consisting of 0.5% methylcellulose and 0.025% Tween 20. Dosages: 0.001-1 mg/kg Administration: Oral gavage 4 hours before LPS administration (Only for Reference)

References

Solubility (25°C)

In vitro	DMSO	96 mg/mL (201.13 mM)
	Ethanol	7 mg/mL (14.66 mM)
	Water	Insoluble
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 2% DMSO+30% PEG 300+5% Tween 80+ddH2O For best results, use promptly after mixing.	5mg/mL

* 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.

Chemical Information Download PH-797804 SDF

Molecular Weight	477.3
Formula	C₂₂H₁₉BrF₂N₂O₃
CAS No.	586379-66-0
Storage	3 years -20°C powder
Storage	2 years -80°C in solvent
Synonyms	N/A
Smiles	CNC(=O)C1=CC(=C(C)C=C1)N2C(=CC(=C(Br)C2=O)OCC3=CC=C(F)C=C3F)C

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p38 MAPK Signaling Pathway Map

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PH-797804