p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK) (p38 MAPK and JNK)

p38 mitogen-activated protein kinases (p38 MAPK) and c-Jun N-terminal kinases (JNK) are two distinct subfamilies of the mitogen-activated protein kinase (MAPK) superfamily, collectively known as stress-activated protein kinases (SAPKs) [PMID: 10851172]. These kinases are activated by a variety of environmental stressors, such as UV radiation and oxidative stress, as well as pro-inflammatory cytokines like TNF-alpha and IL-1beta [PMID: 11527454]. p38 MAPK is a key regulator of the inflammatory response, primarily by controlling the production of cytokines, whereas JNK is heavily involved in regulating apoptosis, cell growth, and metabolic processes [PMID: 16446357]. Both pathways are significant therapeutic targets for chronic inflammatory conditions, including rheumatoid arthritis and Crohn's disease, and are also implicated in cancer and neurodegenerative disorders [PMID: 22414318]. Although many potent inhibitors have been developed, their clinical utility has been limited by significant toxicities, such as hepatotoxicity and CNS effects, and the inherent complexity of the MAPK signaling network [PMID: 19157854].

Other names

Stress-activated protein kinasesSAPKMAPK14MAPK11MAPK12MAPK13MAPK8MAPK9MAPK10p38-alphaJNK1JNK2JNK3

Small molecule inhibition of the ATP-binding pocket of p38 and JNK kinases, preventing the phosphorylation of downstream transcription factors and signaling proteins, which subsequently inhibits the production of pro-inflammatory cytokines and modulates stress-induced cellular responses [PMID: 11527454, PMID: 16446357].