title: Pursuing aldose reductase inhibitors through in situ cross-docking and similarity-based virtual screening.
abstract: 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.
authors.affiliation: Dipartimento di Chimica Farmaceutica e Tossicologica, Universita di Napoli "Federico II", Via D. Montesano 49, 80131 Napoli, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Cosconati
authors.forename: Luciana
authors.initials: L
authors.lastname: Marinelli
authors.forename: Concettina
authors.initials: C
authors.lastname: La Motta
authors.forename: Stefania
authors.initials: S
authors.lastname: Sartini
authors.forename: Federico
authors.initials: F
authors.lastname: Da Settimo
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Olson
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D008958:Models, Molecular; D011487:Protein Conformation; D014584:User-Computer Interface
chemical_list: D004791:Enzyme Inhibitors; D008024:Ligands; D000449:Aldehyde Reductase