Pursuing Aldose Reductase Inhibitors through in Situ Cross-Docking and Similarity-Based Virtual Screening

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• 作者：Sandro Cosconati ; Luciana Marinelli ; Concettina La Motta ; Stefania Sartini ; Federico Da Settimo ; Arthur J. Olson ; Ettore Novellino
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：September 24, 2009
• 年：2009
• 卷：52
• 期：18
• 页码：5578-5581
• 全文大小：805K
• 年卷期：v.52,no.18(September 24, 2009)
• ISSN：1520-4804

文摘

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 IC₅₀ below 3 μM. Six new compounds, structurally unrelated to the known ARIs, have been identified, opening up opportunity for lead optimization.