Selective benzimidazole inhibitors of the antigen receptor-mediated NF-kappaB activation pathway

Bioorg Med Chem. 2010 Mar 1;18(5):1918-24. doi: 10.1016/j.bmc.2010.01.039. Epub 2010 Jan 25.

Abstract

Dysregulated antigen receptor-mediated NF-kappaB activation can contribute to development of autoimmunity, chronic inflammation, and malignancy. A chemical biology screening strategy has identified a substituted benzimidazole that selectively inhibits antigen receptor-mediated NF-kappaB activation without blocking other NF-kappaB activation pathways. A library of analogs was synthesized and the structure-activity relationship and metabolic stability for the series is presented.

Publication types

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

MeSH terms

  • Benzimidazoles / chemical synthesis
  • Benzimidazoles / chemistry*
  • Benzimidazoles / pharmacology
  • Humans
  • Microsomes, Liver / metabolism
  • NF-kappa B / metabolism*
  • Receptors, Antigen / antagonists & inhibitors*
  • Receptors, Antigen / metabolism
  • Signal Transduction
  • Structure-Activity Relationship
  • Transcriptional Activation

Substances

  • Benzimidazoles
  • NF-kappa B
  • Receptors, Antigen