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Development of Noviomimetics as C-Terminal Hsp90 Inhibitors.

ABSTRACT: KU-32 and KU-596 are novobiocin-derived, C-terminal heat shock protein 90 (Hsp90) modulators that induce Hsp70 levels and manifest neuroprotective activity. However, the synthetically complex noviose sugar requires 10 steps to prepare, which makes translational development difficult. In this study, we developed a series of "noviomimetic" analogues of KU-596, which contain noviose surrogates that can be easily prepared, while maintaining the ability to induce Hsp70 levels. Both sugar and sugar analogues were designed, synthesized, and evaluated in a luciferase reporter assay, which identified compound 37, a benzyl containing noviomimetic, as the most potent inducer of Hsp70.

SUBMITTER: Anyika M

PROVIDER: S-EPMC4716602 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Development of Noviomimetics as C-Terminal Hsp90 Inhibitors.

Anyika Mercy M McMullen Mason M Forsberg Leah K LK Dobrowsky Rick T RT Blagg Brian S J BS

ACS medicinal chemistry letters 20151209 1

KU-32 and KU-596 are novobiocin-derived, C-terminal heat shock protein 90 (Hsp90) modulators that induce Hsp70 levels and manifest neuroprotective activity. However, the synthetically complex noviose sugar requires 10 steps to prepare, which makes translational development difficult. In this study, we developed a series of "noviomimetic" analogues of KU-596, which contain noviose surrogates that can be easily prepared, while maintaining the ability to induce Hsp70 levels. Both sugar and sugar an ...[more]

PMID: 26819668

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