Development of the first non-hydroxamate selective HDAC6 degraders

04 July 2022, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

The targeted degradation of histone deacetylase 6 (HDAC6) by heterobifunctional degraders constitutes a promising approach to treat HDAC6-driven diseases. Previous HDAC6 selective degraders utilised a hydroxamic acid as a zinc-binding group (ZBG) which features mutagenic and genotoxic potential. Here we report the development of a new class of selective HDAC6 degraders based on a difluoromethyl-1,3,4-oxadiazole (DFMO) warhead as ZBG.

Keywords

PROTAC
HDAC
Degrader
cancer

Supplementary materials

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Description
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Supplementary Information
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Supplementary Figures, Schemes and Tables, experimental procedures, 1H NMR, 13C NMR and MS data, docking protocols
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