Discovery of covalent enzyme inhibitors using virtual docking of covalent fragments

Bioorg Med Chem Lett. 2019 Jan 1;29(1):36-39. doi: 10.1016/j.bmcl.2018.11.019. Epub 2018 Nov 9.

Abstract

Here we present a virtual docking screen of 1648 commercially available covalent fragments, and identified covalent inhibitors of cysteine protease cathepsin L. These inhibitors did not inhibit closely related protease cathepsin B. Thus, we have established virtual docking of covalent fragments as an approach to discover covalent enzyme inhibitors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cathepsin L / antagonists & inhibitors*
  • Cathepsin L / metabolism
  • Cysteine Proteinase Inhibitors / chemical synthesis
  • Cysteine Proteinase Inhibitors / chemistry
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Drug Evaluation, Preclinical
  • Humans
  • Molecular Docking Simulation*
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Cysteine Proteinase Inhibitors
  • CTSL protein, human
  • Cathepsin L