PH-797804

586379-66-0

C22H19BrF2N2O3

DMSO : 50 mg/mL (104.76 mM; Need ultrasonic)

MAPK/ERK Pathway

PH-797804 is a novel pyridinone inhibitor of p38alpha with IC50 of 26 nM; 4-fold more selective versus p38beta and does not inhibit JNK2. IC50 value: 26 nM [1] Target: p38alphaMAPK in vitro: PH-797804 blocks LPS-induced TNF-alpha 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 uM. 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 uM (unless specified): CDK2, ERK2, IKK1, IKK2, IKKi, MAPKAP2, MAPKAP3, MKK7 (>100 uM), MNK, MSK (>164 uM), 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-alpha, IL-6, and MK-2 activity in a dose- and concentration-dependent manner in a human endotoxin challenge model [1].