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Updated: Mar 26, 2026

Malachite Green Assay for the Discovery of Heat-Shock Protein 90 Inhibitors
Published on: January 20, 2023
Development of Noviomimetics as C-Terminal Hsp90 Inhibitors
Mercy Anyika1, Mason McMullen2, Leah K Forsberg1
1Department of Medicinal Chemistry, The University of Kansas , 1251 Wescoe Hall Drive, Malott 4070, Lawrence, Kansas 66045-7563, United States.
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.
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