Pursuing aldose reductase inhibitors through in situ cross-docking and similarity-based virtual screening

J Med Chem. 2009 Sep 24;52(18):5578-81. doi: 10.1021/jm901045w.


Aldose reductase (ALR2) is a critical enzyme in the development of the major complications of diabetes mellitus. Herein, new molecular entities active against ALR2 were discovered through an integrated receptor- and ligand-based virtual screening campaign. Twelve candidates were found to inhibit this enzyme in the micromolar range including two ligands having an IC(50) below 3 muM. Six new compounds, structurally unrelated to the known ARIs, have been identified, opening up opportunity for lead optimization.

MeSH terms

  • Aldehyde Reductase / antagonists & inhibitors*
  • Aldehyde Reductase / chemistry
  • Drug Evaluation, Preclinical / methods*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Ligands
  • Models, Molecular
  • Protein Conformation
  • User-Computer Interface


  • Enzyme Inhibitors
  • Ligands
  • Aldehyde Reductase