Inhibitors of p38 mitogen-activated protein kinase for the treatment of rheumatoid arthritis.
The p38 mitogen-activated protein kinase pathway is involved in a number of cellular processes critical to the development of rheumatoid arthritis. The activation and infiltration of leukocytes as well as the production of inflammatory cytokines are p38-dependent processes. In addition, p38 regulates the differentiation of osteoclasts, which are directly involved in bone loss. Numerous inhibitors of p38 have demonstrated efficacy in animal models of arthritic disease and at least two p38 inhibitors are currently in phase II clinical trials for rheumatoid arthritis. Several other p38 inhibitors are currently undergoing phase I clinical trials.