In vitro activity: SB-242235 is a potent and selective p38 MAP kinase inhibitor with IC50 of 1.0 uM and has the potential for treatment of cytokine-mediated diseases like autoimmune or inflammatory diseases. SB-242235 showed favorable pharmacokinetic properties. Systemic plasma clearance was high in rat, but in the non-rodent species SB-242235 demonstrated low to moderate clearance with plasma half-lives> 4h. Oral bioavailability in each preclinical species was high. In rat and monkey, SB-242235 demonstrated non-linear elimination kinetics that manifested as a decrease in clearance with increasing dose and apparent oral bioavailability> 100% at high oral doses.

Kinase Assay: SB 242235 inhibited intracellular p38 activity, human chondrocytes were treated with different doses of SB 242235 prior to stimulation with IL-1_ for 15 min. MAPKAP K2 was then isolated from these cells and assayed using HSP27 as a substrate. SB 242235 dose-dependently inhibited the activation of MAPKAP K2 with an IC50 of 1.0 uM

Cell Assay: SB 242235 inhibited intracellular p38 activity, human chondrocytes were treated with different doses of SB 242235 prior to stimulation with IL-1_ for 15 min. MAPKAP K2 was then isolated from these cells and assayed using HSP27 as a substrate. SB 242235 dose-dependently inhibited the activation of MAPKAP K2 with an IC50 of 1.0 uM.