Biological Activity
CP-863187 is a potent p38α (p38α) inhibitor (IC50 = 5.8 nM) with 44-fold selectivity over p38β (p38β) and no inhibitory potency against p38γ (p38γ) and p38δ (p38δ) isoforms. CP-863187 effectively inhibits LPS-stimulated cellular TNF-α production in vitro (IC50 = 259 and 25 nM, using human whole blood and isolated mononuclear cells, respectively) and in rats in vivo (ED50 = 0.3 mg/kg p.o.) with good pharmacokinetic profile and oral availability (F = 87%/dog, 40%/monkey, 30%/r at with 5 mg/kg oral dosage; F = 66%/r at with 50 mg/kg oral dosage).
