The discovery of novel tartrate-based TNF-alpha converting enzyme (TACE) inhibitors

Bioorg Med Chem Lett. 2010 Feb 1;20(3):1189-93. doi: 10.1016/j.bmcl.2009.12.004. Epub 2009 Dec 5.

Abstract

A novel series of TNF-alpha convertase (TACE) inhibitors which are non-hydroxamate have been discovered. These compounds are bis-amides of L-tartaric acid (tartrate) and coordinate to the active site zinc in a tridentate manner. They are selective for TACE over other MMP's. We report the first X-ray crystal structure for a tartrate-based TACE inhibitor.

Publication types

  • Comparative Study

MeSH terms

  • ADAM Proteins / antagonists & inhibitors*
  • ADAM Proteins / metabolism*
  • ADAM17 Protein
  • Binding Sites
  • Combinatorial Chemistry Techniques
  • Crystallography, X-Ray
  • Drug Discovery* / methods
  • Humans
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / metabolism
  • Protease Inhibitors / pharmacology
  • Tartrates / chemistry*
  • Tartrates / metabolism
  • Tartrates / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Protease Inhibitors
  • Tartrates
  • Tumor Necrosis Factor-alpha
  • ADAM Proteins
  • ADAM17 Protein
  • ADAM17 protein, human

Associated data

  • PDB/3KME