The p38 mitogen-activated protein kinase (MAPK) is considered as a key signal transduction pathway which is crucial for the induction and maintenance of chronic inflammation. The p38 MAPK covers a central role in the regulation of IL-1beta and TNF-alpha signalling network at both the transcriptional and translational level. Numerous inhibitors of p38 MAPK have been described in vitro in the last decade. Their discovery was facilitated by availability of crystallographic data. However, first generation p38 MAPK inhibitors suffered from side effects. Next generation projects selectively target the p38 alpha site and avoid docking at the ATP-binding site. A number of p38 MAPK are in active phase II studies, mainly in rheumatoid arthritis and psorariasis, but uses in chronic obstructive pulmonary disease, atherosclerosis, neuropathic pain and hematologic malignancies are also clinically evaluated. Among the clinical protagonists are Bristol-Myers Squibb, Roche, Pfizer, GlaxoSmithKline and Mitsubishi Tanabe Pharma.

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