MAP Kinase-MEK Inhibitors
Mitogen-activated protein kinases (MAP kinases) are Serine/Threonine phosphorylating enzymes which function in a cascade typically involving at least 3 enzymes which get activated in a series by sequential phosphorylation events. These enzymes collectively coordinate cellular responses to various stimuli (growth factors or mitogens, cytokines, hormones, osmotic stress, heat-shock, viral infections) resulting in gene regulation (mRNA transcription and protein translation), immune reactions, cell division, differentiation, migration and programmed cell-death. This is why they are also called Extracellular signal-regulated kinases (ERKs). Any extracellular signal binding to the concomitant membrane receptor (typically a G-protein coupled receptor) is transduced via a GTPase resulting in activation of MAP3K (e.g. Raf), which in turn activates MAP2K (e.g. MEK1 and MEK2), which activates MAPK (e.g. ERK1, ERK2, p38 kinases, ERK5 etc.). Activated MAPK can relay the signal to a large array of downstream effector molecules including transcription factors. This can ultimately result in regulation of gene expression. Aberrant signaling through the MAPK pathway results in many of the hallmarks of cancer, including abnormal cellular proliferation, impaired apoptosis, increased angiogenesis, metastasis and the development of drug resistance. Thus participants in this pathway are appealing candidates for the development of new therapies to treat various malignancies. BioVision offers a collection of inhibitors targeting various steps of the MAPK pathway.
