Allosteric Indole Amide Inhibitors of p97: Identification of a Novel Probe of the Ubiquitin Pathway

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• 作者：Celeste Alverez ; Stacie L. Bulfer ; Ramappa Chakrasali ; Michael. S. Chimenti ; Raymond J. Deshaies ; Neal Green ; Mark Kelly ; Matthew G. LaPorte ; Taber S. Lewis ; Mary Liang ; William J. Moore ; R. Jeffrey Neitz ; Vsevolod A. Peshkov ; Michael A. Walters ; Feng Zhang ; Michelle R. Arkin ; Peter Wipf ; Donna M. Huryn
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：February 11, 2016
• 年：2016
• 卷：7
• 期：2
• 页码：182-187
• 全文大小：437K
• ISSN：1948-5875

文摘

A high-throughput screen to discover inhibitors of p97 ATPase activity identified an indole amide that bound to an allosteric site of the protein. Medicinal chemistry optimization led to improvements in potency and solubility. Indole amide 3 represents a novel uncompetitive inhibitor with excellent physical and pharmaceutical properties that can be used as a starting point for drug discovery efforts.