SB-242235

A selective p38 MAPK inhibitor; inhibits IL-1 beta induction of p38 MAPK in primary human chondrocytes with IC50 of 1 uM; inhibits LPS-stimulated serum levels of TNFalpha in normal rats with mean ED50 of 3.99 mg/kg.Rheumatoid Arthritis Discontinued(In Vitro):SB 242235 (0-10 μM) dose-dependently inhibits the activation of MAPKAP K2 with an IC50 of 1.0 μM in human chondrocytes stimulated with IL-1β.SB 242235 inhibits intracellular p38 activity, MAPKAP K2 was then isolated from these cells and assayed using HSP27 as a substrate.(In Vivo):SB242235 (100 mg/kg; p.o.) abolishes MAP-KAPK-2 activity and HSP27 phosphorylation.SB242235 inhibits expression of the pro-inflammatory cytokines interleukin (IL)-6 and KC (murine IL-8) and COX-2.SB-242235 is demonstrated non-linear elimination kinetics that manifested as a decrease in clearance with increasing dose and apparent oral bioavailability > 100% at high oral doses in rat and monkey.