Development of the first non-hydroxamate selective HDAC6 degraders.

Tim Keuler,Beate König,Nico Bückreiß,Fabian B Kraft, Philipp König,Linda Schäker-Hübner,Christian Steinebach,Gerd Bendas,Michael Gütschow,Finn K Hansen

Chemical communications (Cambridge, England)（2022）

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摘要

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 warhead as ZBG.

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关键词

PROTAC,HDAC,Degrader,cancer

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