The p38 MAPK Inhibitors and Their Role in Inflammatory Diseases

The p38 family is a highly evolutionarily conserved group of mitogen-activated protein kinases (MAPKs) that is involved in and helps co-ordinate cellular responses to nearly all stressful stimuli. Four isoforms of the p38 MAPK family (alpha, beta, gamma, delta) have been identified. p38 alpha is activated by many inflammatory stimuli, and it plays a key role in regulating the biosynthesis of proinflammatory cytokines like interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha). For this reason, p38 MAPK is an important target to be studied for the treatment of chronic airway inflammatory diseases, rheumatoid arthritis, inflammatory bowel disease, Alzheimer's disease, atherosclerosis, COVID-19 and acute coronary syndrome. The characteristics of p38 MAPK, the different modes of inhibition, and its involvement in inflammatory diseases are summarized in this review. We then discuss the p38 MAPK inhibitors that have been used in the in vitro systems as well as in the clinical trials.