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

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.

doi:10.1021/acsmedchemlett.5b00396.s001

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

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posted on 2016-02-05, 14:58 authored by 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

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.

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PathwayA Novel Probe Identification protein p 97 ATPase activity drug discovery efforts indole amide Indole amide 3 Medicinal chemistry optimization solubility Allosteric Indole Amide Inhibitors potency inhibitor allosteric site Ubiquitin

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

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