A metal-based inhibitor of tumor necrosis factor-α

Angew Chem Int Ed Engl. 2012 Sep 3;51(36):9010-4. doi: 10.1002/anie.201202937. Epub 2012 Jul 13.

Abstract

Staying in the pocket: A cyclometalated iridium(III) biquinoline complex targets the protein-protein interface (see picture; C yellow, N blue, Ir dark green) of the tumor necrosis factor-α (TNF-α) trimer. Molecular-modeling studies confirm the nature of this interaction. Both enantiomers of the iridium complex display comparable in vitro potency to the strongest small-molecule inhibitor of TNF-α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Coordination Complexes / chemistry*
  • Crystallography, X-Ray
  • Hep G2 Cells
  • Humans
  • Immobilized Proteins / antagonists & inhibitors
  • Immobilized Proteins / metabolism
  • Iridium / chemistry*
  • Protein Interaction Maps
  • Protein Structure, Tertiary
  • Receptors, Tumor Necrosis Factor, Type I / antagonists & inhibitors
  • Receptors, Tumor Necrosis Factor, Type I / metabolism
  • Stereoisomerism
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Coordination Complexes
  • Immobilized Proteins
  • Receptors, Tumor Necrosis Factor, Type I
  • Tumor Necrosis Factor-alpha
  • Iridium