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

Basic Information

ID: ALA4715707

Journal: ACS Med Chem Lett

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

Authors: Alverez C,Bulfer SL,Chakrasali R,Chimenti MS,Deshaies RJ,Green N,Kelly M,LaPorte MG,Lewis TS,Liang M,Moore WJ,Neitz RJ,Peshkov VA,Walters MA,Zhang F,Arkin MR,Wipf P,Huryn DM

Abstract: 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.

CiteXplore: 26985295

DOI: 10.1021/acsmedchemlett.5b00396

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