BAY 11-7082 Is a Broad-Spectrum Inhibitor With Anti-Inflammatory Activity Against Multiple Targets

Mediators Inflamm. 2012;2012:416036. doi: 10.1155/2012/416036. Epub 2012 Jun 15.

Abstract

BAY 11-7082 (BAY) is an inhibitor of κB kinase (IKK) that has pharmacological activities that include anticancer, neuroprotective, and anti-inflammatory effects. In this study, BAY-pharmacological target pathways were further characterized to determine how this compound simultaneously suppresses various responses. Primary and cancerous (RAW264.7 cells) macrophages were activated by lipopolysaccharide, a ligand of toll-like receptor 4. As reported previously, BAY strongly suppressed the production of nitric oxide, prostaglandin E(2), and tumor necrosis factor-α and reduced the translocation of p65, major subunit of nuclear factor-κB, and its upstream signaling events such as phosphorylation of IκBα, IKK, and Akt. In addition, BAY also suppressed the translocation and activation of activator protein-1, interferon regulatory factor-3, and signal transducer and activator of transcription-1 by inhibiting the phosphorylation or activation of extracellular signal-related kinase, p38, TANK-binding protein, and Janus kinase-2. These data strongly suggest that BAY is an inhibitor with multiple targets and could serve as a lead compound in developing strong anti-inflammatory drugs with multiple targets in inflammatory responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Dinoprostone / genetics
  • Dinoprostone / metabolism
  • Humans
  • Immunoblotting
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Nitriles / pharmacology*
  • Sulfones / pharmacology*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • 3-(4-methylphenylsulfonyl)-2-propenenitrile
  • Anti-Inflammatory Agents
  • NF-kappa B
  • Nitriles
  • Sulfones
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Dinoprostone