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New small-molecule inhibitors of mitogen-activated protein kinase kinase

Julie A Spicer1

  • 1University of Auckland, Faculty of Medical and Health Sciences, Auckland Cancer Society Research Centre, Private Bag 92019, Auckland 1142, New Zealand +64 9 3737599, ext. 86149 ; +64 9 3737502 ; j.spicer@auckland.ac.nz.

Expert Opinion on Drug Discovery
|March 19, 2013
PubMed
Abstract

Insights

Mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitors show promise for cancer therapy. Recent advancements in selective MEK1/2 inhibitors, including allosteric compounds, are paving the way for combination treatments and targeted therapies.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Oncology

Background:

  • The Ras/Raf/MEK/ERK pathway is crucial for tumor growth and survival.
  • This pathway is also implicated in inflammatory and developmental disorders.
  • Inhibition of mitogen-activated protein kinase kinase 1/2 (MEK1/2) is a key therapeutic strategy.

Purpose of the Study:

  • To discuss the significance of the mitogen-activated protein kinase (MAPK) pathway.
  • To highlight MEK1/2 as a therapeutic target.
  • To review recent patent activity concerning MEK1/2 inhibitors.

Main Methods:

  • Searched patent literature for MEK1/2 inhibitors within the last three years.
  • Included relevant publications on compound discovery and development.

Main Results:

  • Crystal structure determination enabled the design of selective and potent MEK1/2 inhibitors.
  • Several allosteric MEK1/2 inhibitors have entered clinical trials.
  • These inhibitors demonstrated some efficacy as single agents in cancer treatment.

Conclusions:

  • Future applications of MEK1/2 inhibitors likely involve combination therapies.
  • MEK1/2 inhibitors may be effective in genetically defined disorders dependent on the MAPK pathway.

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