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MEK Inhibitor Mechanism of Action, Side Effects, and Uses
Metastatic melanoma is a deadly cancer for which conventional chemotherapy provides little benefit. However, newer therapies involving a pathway called the mitogen-activated protein kinase (MAPK) pathway have demonstrated success in inducing remission.

The MAPK pathway is more accurately termed the RAS-RAF-MEK-ERK pathway, and involves the regulation of cell proliferation and survival. It is constitutionally overactive in 30% of cancers. Two enzymes in this pathway, namely, BRAF and MEK, are target kinases which play crucial roles in the cell cycle.

The first therapies to target this pathway were BRAF inhibitors, but intrinsic and acquired tumor resistance quickly led to treatment failure by reactivation of the MAPK pathway. MEK inhibitors have emerged to partially overcome these resistance mechanisms and are now used in combination with BRAF inhibitors to extend the time to resistance.

MEK is a dual specificity threonine/tyrosine kinase, so called from the term MAPK/ERK kinase. It is a key effector of the three-layered RAS/RAF/MEK/ERK signaling cascade, expressed by seven genes from MAPK1 to MAPK7.

MEK inhibitors bind to and inhibit MEK, inhibiting MEK-dependent cell signaling. This inhibition leads to cell death and the inhibition of tumor growth. These are allosteric binding inhibitors of MEK which inhibit either MEK1 alone, or both MEK1 and MEK2.

What is the mechanism of action of MEK inhibitors?
http://www.medchemhub.com/mek-inhibitors/mek-inhibitor-selumetinib.html