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.