Application of virtual screening to the discovery of novel nicotinamide phosphoribosyltransferase (NAMPT) inhibitors with potential for the treatment of cancer and axonopathies

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• 作者：David E. Clark^a ; ^{david.clark@crl.com" class="auth_mail" title="E-mail the corresponding author} ; Bohdan Waszkowycz^a ; ^&dagger ; ; Melanie Wong^a ; Peter M. Lockey^a ; Robert Adalbert^c ; ^&Dagger ; ; Jonathan Gilley^c ; ^&Dagger ; ; Jonathan Clark^b ; Michael P. Coleman^c ; ^&Dagger ;
• 关键词：NAMPT ; Virtual screening ; Axon degeneration ; Molecular docking ; Similarity searching
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：15 June 2016
• 年：2016
• 卷：26
• 期：12
• 页码：2920-2926
• 全文大小：3052 K

文摘

NAMPT may represent a novel target for drug discovery in various therapeutic areas, including oncology and inflammation. Additionally, recent work has suggested that targeting NAMPT has potential in treating axon degeneration. In this work, publicly available X-ray co-crystal structures of NAMPT and the structures of two known NAMPT inhibitors were used as the basis for a structure- and ligand-based virtual screening campaign. From this, two novel series of NAMPT inhibitors were identified, one of which showed a statistically significant protective effect when tested in a cellular model of axon degeneration.