期刊
CHEMISTRYSELECT
卷 6, 期 23, 页码 5729-5742出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/slct.202100406
关键词
drug design; inflammation; mitogen-activated protein kinase; p38 MAPK inhibition; protein structures
资金
- Coordination for the Improvement of Higher Education Personnel - Brasil (CAPES) [001]
- CNPQ (National Council of Research of Brazil)
The p38 family of mitogen-activated protein kinases is highly conserved and plays a key role in coordinating cellular responses to stressful stimuli. The alpha isoform, p38α, is particularly important in inflammatory responses and is a target for the treatment of various 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.
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