Mitogen-activated Protein Kinases (MAPK)
Mitogen-activated protein kinases [(MAPKs), also referred to as extracellular signal-regulated kinases (ERKs)] are a family of serine/threonine protein kinases that mediate fundamental biological processes and cellular responses to external stress signals.  MAPK signaling cascades control complex programs, such as homeostasis and acute hormonal responses, embryogenesis, differentiation, proliferation and cell death.  MAPKs lie within protein kinase cascades and each cascade consists of more than three enzymes that are activated in series: a MAPK kinase kinase kinase (MAPKKK, MAP3K), a MAPK kinase kinase (MAPKK, MAP2K, MEK) and a MAP kinase (MAPK). Raf-1 is a member of the MAP3K family. Raf-1 inhibitors are currently under development, including, for example, BAY 439006 and sorafenib. MEK inhibitors including MEK1 and MEK2 inhibitors, are being developed as therapeutic agents for the treatment of cancer. MAPK inhibitors are a potential new therapy for Rheumatoid Arthritis.  In mammalian cells, three MAPK families have been clearly characterized: namely classical MAPK (ERK), C-Jun N-terminal kinse/ stress-activated protein kinase (JNK/SAPK) and p38 kinase. Selective inhibition of ERK represents a potential approach for the treatment of cancer and other diseases. JNK activation is associated with transformation in many oncogene and growth factor-mediated pathways.  p38 is involved in various vertebrate cell differentiation processes. Pyridinylimidazole compounds are selective inhibitors of p38 MAPK, inhibiting the catalytic activity of the kinase by competitive binding in its ATP pocket.
Reference Learn More
 Seger R, et al. The MAK signaling cascade. The FASEB journal. 1995, 9, 9: 726-735.
 Ohori M, et al. ERK inhibitors as a potential new therapy for Rheumatoid Arthritis. Drug New & Perspectives. 2008, 21(5): 245.
 Ohori M, et al. Identification of a selective ERK inhibitor and structural determination of the inhibitor-ERK2 complex. Biochemical and Biophysical Research Communications. 2005, 336: 357-363.
 Zhang W, et al. MAPK signal pathways in the regulation of cell proliferation in mammalian cells. Cell Res. 2002, 12(1): 9-18.
 Kaminska B, et al. MAPK signalling pathways as molecular targets for anti-inflammatory therapy-from molecular mechanisms to therapeutic benefits. Biochim Biophys Acta. 2005.1754(1-2): 253-262.
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