Biochem/physiol Actions
CP-9446219 is a potent p38alpha (p38α) inhibitor (IC50 = 1.8 nM) with no inhibitory potency against a panel of 26 other knases (IC50 >10 μM), including p38gamma (p38γ) and p38delta (p38δ), MKK1, MAPK2/ERK2, JNK, MAPKAP-K1a, and MAPKAP-K2. CP-944629 effectively inhibits LPS-stimulated cellular TNF-α production in vitro (IC50 = 63 and 8.3 nM, using human whole blood and isolated mononuclear cells, respectively) and in rats in vivo (ED50 = 0.1 mg/kg p.o.) with good pharmacokinetic profile and oral availability (F = 66%/monkey, 54%/rat).
