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A MEK inhibitor is a chemical or drug that inhibits the mitogen-activated protein kinase kinase enzymes MEK1 and/or MEK2. They can be used to affect the MAPK/ERK pathway which is often overactive in some cancers.
A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of serine/threonine-specific protein kinases involved in directing cellular responses to a diverse array of stimuli, such as mitogens, osmotic stress, heat shock and proinflammatory cytokines.
Oxidative stress is the most powerfully specific stress activating p38 MAPK. [7] Abnormal activity (higher or lower than physiological) of p38 has been implicated in pathological stresses in several tissues, that include neuronal, [8] [9] [10] bone, [11] lung, [12] cardiac and skeletal muscle, [13] [14] red blood cells, [15] and fetal tissues. [16]
Binimetinib is an orally available inhibitor of mitogen-activated protein kinase kinase (MEK), or more specifically, a MAP2K inhibitor. [9] MEK is part of the RAS pathway, which is involved in cell proliferation and survival. MEK is upregulated in many forms of cancer. [10]
The first drug licensed to act on this pathway is sorafenib — a Raf kinase inhibitor. Other Raf inhibitors include SB590885, PLX4720, XL281, RAF265, encorafenib , dabrafenib , and vemurafenib . [ 18 ]
Selumetinib is a kinase inhibitor, more specifically a selective inhibitor of the enzyme mitogen-activated protein kinase kinase (MAPK kinase or MEK) subtypes 1 and 2. These enzymes are part of the MAPK/ERK pathway, which regulates cell proliferation (i.e., growth and division) and is overly active in many types of cancer. [18]
It is a highly selective inhibitor of both MEK1 and MEK2, a type of MAPK/ERK kinase. [ 10 ] [ 11 ] U0126 was found to functionally antagonize AP-1 transcriptional activity via noncompetitive inhibition of the dual specificity kinase MEK with IC 50 of 72 nM for MEK1 and 58 nM for MEK2.
A protein kinase inhibitor (PKI) is a type of enzyme inhibitor that blocks the action of one or more protein kinases. Protein kinases are enzymes that phosphorylate (add a phosphate , or PO 4 , group) to a protein and can modulate its function.
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