Discovery of inhibitors of the channel-activating protease prostasin (CAP1/PRSS8) utilizing structure-based design

Bioorg Med Chem Lett. 2008 Nov 15;18(22):5895-9. doi: 10.1016/j.bmcl.2008.08.029. Epub 2008 Aug 14.

Abstract

Structure-based design was utilized to guide the early stage optimization of a substrate-like inhibitor to afford potent peptidomimetic inhibitors of the channel-activating protease prostasin. The first X-ray crystal structures of prostasin with small molecule inhibitors bound to the active site are also reported.

MeSH terms

  • Combinatorial Chemistry Techniques
  • Crystallography, X-Ray
  • Molecular Mimicry
  • Molecular Structure
  • Protein Conformation
  • Serine Endopeptidases / drug effects*
  • Serine Proteinase Inhibitors / chemical synthesis*
  • Serine Proteinase Inhibitors / chemistry
  • Serine Proteinase Inhibitors / pharmacology*
  • Structure-Activity Relationship

Substances

  • Serine Proteinase Inhibitors
  • Serine Endopeptidases
  • prostasin