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

作者：Alverez Celeste; Bulfer Stacie L; Chakrasali Ramappa; Chimenti Michael S; Deshaies Raymond J; Green Neal; Kelly Mark; LaPorte Matthew G; Lewis Taber S; Liang Mary; Moore William J; Neitz R Jeffrey; Peshkov Vsevolod A; Walters Michael A; Zhang Feng; Arkin Michelle R^*; Wipf Peter^*; Huryn Donna M^*

来源：ACS Medicinal Chemistry Letters, 2016, 7(2): 182-187.

DOI：10.1021/acsmedchemlett.5b00396

• AAA ATPase
• p97 inhibitor
• allosteric inhibitor
• indole amide
• protein homeostasis
• ubiquitin pathway modulator

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.

• 出版日期2016-2