A selective p38 MAPK inhibitor
PH-797804 is a novel, potent, ATP-competitive and reversible inhibitor of human p38 MAP kinase. It specifically inhibits p38α with IC50?value of 26 nM and K(i) value of 5.8 nM.
PH-797804 inhibits LPS induced TNF-α and IL-1β?production in monocytes with a concentration-dependently manner. PH-797804 blocks RANKL and M-CSF induced osteoclast formation in primary rat bone marrow cells.
Orally administered PH-797804 suppresses TNF-α level in a dose-dependent manner in LPS induced Lewis rats and also in cynomolgus monkeys. Additionally, PH-797804 has been shown to inhibit chronic inflammation in arthritis models induced by mouse collagen-induced or rat streptococcal cell wall (SCW) extract.
参考文献:
[1] Hope HR1,?Anderson GD,?Burnette BL,?Compton RP,?Devraj RV,?Hirsch JL,?Keith RH,?Li X,?Mbalaviele G,?Messing DM,?Saabye MJ,Schindler JF,?Selness SR,?Stillwell LI,?Webb EG,?Zhang J,?Monahan JB. Anti-inflammatory properties of a novel N-phenyl pyridinone inhibitor of p38 mitogen-activated protein kinase: preclinical-to-clinical translation. J Pharmacol Exp Ther.?2009 Dec;331(3):882-95.
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