Abstract
Mitogen-activated protein kinases (MAP kinases) are a family of kinases that regulates a range of biological processes implicated in the response to growth factors like latelet-derived growth factor (PDGF), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and stress, such as ultraviolet irradiation, heat shock, and osmotic shock. The MAP kinase family consists of four major subfamilies of related proteins (extracellular regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), p38, and extracellular regulated kinase 5 (ERK5)) and regulates numerous cellular activities, such as apoptosis, gene expression, mitosis, differentiation, and immune responses. The deregulation of these kinases is shown to be involved in human diseases, such as cancer, immune diseases, inflammation, and neurodegenerative disorders. The awareness of the therapeutic potential of the inhibition of MAP kinases led to a thorough search for small-molecule inhibitors. Here, we discuss some of the most well-known MAP kinase inhibitors and their use in cancer research.
Highlights
Protein kinases are a family of enzymes that phosphorylate proteins on serine, threonine, or tyrosine
In the past couple of decades, developments in the small-molecule mitogen-activated protein (MAP) kinase inhibitor field have led to quite a number of marketed products with a diverse range of the inhibited targets
Clinical studies with MAP kinase inhibitors ought to determine which MAP kinase inhibitors are most effective for anticancer therapy
Summary
Protein kinases are a family of enzymes that phosphorylate proteins on serine, threonine, or tyrosine. The first MAP kinase network to be discovered was the GTPase Ras-RAF proto-oncogene serine/threonine-protein kinase-extracellular regulated kinase (RAS-RAF-ERK) signal transduction cascade (Figure 1), defined by ERK1 and ERK2 [10,11]. There are three differently spliced genes in the Aberrant activation of JNKs is found in many cancers, as well as inflammatory and neurodegenerative subfamily, namely, JNK1, JNK2, and JNK3. Pathogens or inflammatory stimuli initiate a cascade mediated by p38 kinases and abnormal activity consisting of four isoforms: α, β, γ, and δ [15]. Of the major substrates diseases and further mediated p38 kinases and abnormaldiseases activity ofand these kinasesOne is observed in inflammatory cancers. 5extracellular regulated kinase kinase 5- extracellular regulated kinase 5 (MEK5-ERK5) cascade (Figure 1)
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