Development of the first non-hydroxamate selective HDAC6 degraders

  • Chem Commun (Camb). 2022 Oct 4;58(79):11087-11090. doi: 10.1039/d2cc03712b.
Tim Keuler  1 ,  Beate König  1 ,  Nico Bückreiß  1 ,  Fabian B Kraft  1 ,  Philipp König  1 ,  Linda Schäker-Hübner  1 ,  Christian Steinebach  1 ,  Gerd Bendas  1 ,  Michael Gütschow  1 ,  Finn K Hansen  1
Affiliations
  • 1. Pharmaceutical Institute, University of Bonn, An der Immenburg 4, 53121, Bonn, Germany. [email protected].
PMID: 36098075 DOI: 10.1039/d2cc03712b
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 warhead as ZBG.

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