Development of Noviomimetics as C-Terminal Hsp90 Inhibitors

详细信息    查看全文

• 作者：Mercy Anyika ; Mason McMullen ; Leah K. Forsberg ; Rick T. Dobrowsky ; Brian S. J. Blagg
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：January 14, 2016
• 年：2016
• 卷：7
• 期：1
• 页码：67-71
• 全文大小：391K
• ISSN：1948-5875

文摘

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.