[CAS NO. 586379-66-0] PH-797804

Name: PH-797804
Brand: Arctom Scientific
SKU: SLK-S2726

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PRODUCTS SPECIFICATIONS [586379-66-0]

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Catalog

SLK-S2726

Brand

Selleck

CAS

586379-66-0

DESCRIPTION [586379-66-0]

Overview

MDL	MFCD18251426
Molecular Weight	477.3
Molecular Formula	C22H19BrF2N2O3
SMILES	O=C1N(C(C)=CC(OCC2=C(F)C=C(F)C=C2)=C1Br)C3=CC(C(NC)=O)=CC=C3C

For research use only.

Storage

3 years,-20°C,powder
1 years,-80°C,in solvent

Shipping

Room temperature shipping(Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Concentration Volume Mass	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
50 mM	0.0419 mL	0.2095 mL	0.4190 mL

Description

PH-797804 is a novel pyridinone inhibitor of with 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. 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.

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.

References

[1] Hope HR, et al, J Pharmacol Exp Ther, 2009, 331(3), 882-895.
[2] Xing L, et al. Biochemistry, 2009, 48(27), 6402-6411.

Synonyms

Benzamide, 3-[3-bromo-4-[(2,4-difluorophenyl)methoxy]-6-methyl-2-oxo-1(2H)-pyridinyl]-N,4-dimethyl-

3-[3-Bromo-4-[(2,4-difluorophenyl)methoxy]-6-methyl-2-oxo-1(2H)-pyridinyl]-N,4-dimethylbenzamide

3-Bromo-4-[(2,4-difluorobenzyl)oxy]-1-[5-[(methylamino)carbonyl]-2-methylphenyl]-6-methylpyridin-2(1H)-one

PH 797804