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.
|Autori:||COSCONATI SANDRO; MARINELLI LUCIANA; LA MOTTA CONCETTINA; SARTINI STEFANIA; DA SETTIMO PASSETTI F; OLSON ARTHUR J; NOVELLINO ETTORE|
|Titolo:||Pursuing Aldose Reductase Inhibitors through in Situ Cross-Docking and Similarity-Based Virtual Screening|
|Anno del prodotto:||2009|
|Digital Object Identifier (DOI):||10.1021/jm901045w|
|Appare nelle tipologie:||1.1 Articolo in rivista|