Identification of benzimidazole-based inhibitors of the mitogen activated kinase-5 signaling pathway

Bioorg Med Chem Lett. 2010 May 1;20(9):2892-6. doi: 10.1016/j.bmcl.2010.03.033. Epub 2010 Mar 10.

Abstract

The MEK-signaling pathways are complex but critical signaling cascades that correlate an extracellular signaling event with internal cell processes. To date at least seven MEK isozymes have been identified. MEK5, in particular, is upregulated in multiple forms of tumors. Analysis of the EGF-induced MEK5 signaling cascade in cultured HEK cells has identified compounds that can inhibit MEK5 phosphorylation of ERK5; observed biological activity is dependent on chemical variation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Benzimidazoles / chemical synthesis
  • Benzimidazoles / chemistry*
  • Benzimidazoles / pharmacology
  • Cell Line
  • Epidermal Growth Factor / pharmacology
  • Humans
  • MAP Kinase Kinase 5 / antagonists & inhibitors*
  • MAP Kinase Kinase 5 / metabolism
  • Mitogen-Activated Protein Kinase 7 / metabolism
  • Phosphorylation
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology
  • Signal Transduction / drug effects*

Substances

  • Benzimidazoles
  • Protein Kinase Inhibitors
  • Epidermal Growth Factor
  • Mitogen-Activated Protein Kinase 7
  • MAP Kinase Kinase 5