Structure-activity relationships of benzimidazole-based selective inhibitors of the mitogen activated kinase-5 signaling pathway

Bioorg Med Chem. 2010 Nov 15;18(22):8054-60. doi: 10.1016/j.bmc.2010.09.017. Epub 2010 Oct 19.


In a prior communication we identified a novel class of benzimidazole-based inhibitors of EGF-induced phosphorylation of ERK5. In this paper we examine the biological activity of several 1-isopropyl-4-amino-6-ether linked benzimidazole-based compounds for their ability to selectively inhibit EGF-mediated ERK5 phosphorylation; potential utility of variation at the 6-position was indicated by the initial structural feature survey. Modification of EGF-induced formation of pERK1/2 and pERK5 in HEK293 cells were analyzed by Western blot analysis. Subsequent analysis of selected compounds in a high-throughput multiple kinase scan and the NCI 60-cell-line screen is presented.

Publication types

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

MeSH terms

  • Benzimidazoles / chemical synthesis
  • Benzimidazoles / chemistry*
  • Benzimidazoles / pharmacology
  • Epidermal Growth Factor / metabolism
  • HEK293 Cells
  • Humans
  • Mitogen-Activated Protein Kinase 7 / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinase 7 / metabolism
  • Phosphorylation
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology
  • Signal Transduction
  • Structure-Activity Relationship


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