Identification of potent and selective TACE inhibitors via the S1 pocket

Bioorg Med Chem Lett. 2007 Jan 1;17(1):34-9. doi: 10.1016/j.bmcl.2006.10.004. Epub 2006 Oct 5.

Abstract

By focusing on the P1 portion of the piperidine beta-sulfone ligands we identified a motif that induces selectivity and resulted in a series of TACE inhibitors that demonstrated excellent in vitro potency against isolated TACE enzyme and excellent selectivity over MMPs 1, 2, 9, 13, and 14.

MeSH terms

  • ADAM Proteins / antagonists & inhibitors*
  • ADAM Proteins / chemistry*
  • ADAM17 Protein
  • Crystallography, X-Ray
  • Ligands
  • Metalloendopeptidases / antagonists & inhibitors
  • Piperidines / chemistry
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / isolation & purification*
  • Protease Inhibitors / pharmacology
  • Sulfones / chemistry

Substances

  • Ligands
  • Piperidines
  • Protease Inhibitors
  • Sulfones
  • ADAM Proteins
  • Metalloendopeptidases
  • ADAM17 Protein