Optimization of Phenyl Indole Inhibitors of the AAA+ ATPase p97.
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ABSTRACT:
SUBMITTER: LaPorte MG
PROVIDER: S-EPMC6231190 | biostudies-literature | 2018 Nov
REPOSITORIES: biostudies-literature
Publications
Optimization of Phenyl Indole Inhibitors of the AAA+ ATPase p97.
LaPorte Matthew G MG Burnett James C JC Colombo Raffaele R Bulfer Stacie L SL Alverez Celeste C Chou Tsui-Fen TF Neitz R Jeffrey RJ Green Neal N Moore William J WJ Yue Zhizhou Z Li Shan S Arkin Michelle R MR Wipf Peter P Huryn Donna M DM
ACS medicinal chemistry letters 20180918 11
Optimization of the side-chain of a phenyl indole scaffold identified from a high-throughput screening campaign for inhibitors of the AAA+ ATPase p97 is reported. The addition of an <i>N</i>-alkyl piperazine led to high potency of this series in a biochemical assay, activity in cell-based assays, and excellent pharmaceutical properties. Molecular modeling based on a subsequently obtained cryo-EM structure of p97 in complex with a phenyl indole was used to rationalize the potency of these alloste ...[more]
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