Progress Towards Therapeutic Small Molecule MEK Inhibitors for Use in Cancer Therapy

Title: Progress Towards Therapeutic Small Molecule MEK Inhibitors for Use in Cancer Therapy

Volume: 5 Issue: 2

Author(s): Eli M. Wallace, Joseph P. Lyssikatos, Tammie Yeh, James D. Winkler and Kevin Koch

Affiliation:

Keywords: mek inhibitor, erk, arry-142886 (azd 6244), pd 0325901, ci-1040, cancer, map kinase, kinase inhibitor

Abstract: This paper reviews recent progress in the design and evaluation of MEK inhibitors as cancer therapeutics. Activation of the Ras / Raf / MEK / MAP kinase pathway has been implicated in uncontrolled cell proliferation and tumor growth. Mutated, oncogenic forms of Ras are found in 50% of colon, 90% of pancreatic and 30% of lung cancers. Recently, B-Raf mutations have been identified in more than 60% of malignant melanomas and from 40-70% of papillary thyroid cancers. MEK, a dual specificity kinase, is a key player in this pathway; it is downstream of both Ras and Raf and activates ERK1/2 through phosphorylation of key tyrosine and threonine residues. Representative examples of both ATP competitive and non-competitive inhibitors as well as natural product based inhibitors will be discussed.

Cite this article as:

Wallace M. Eli, Lyssikatos P. Joseph, Yeh Tammie, Winkler D. James and Koch Kevin, Progress Towards Therapeutic Small Molecule MEK Inhibitors for Use in Cancer Therapy, Current Topics in Medicinal Chemistry 2005; 5 (2) . https://dx.doi.org/10.2174/1568026053507723