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
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.
Topics & Concepts
HDAC6ChemistryHydroxamic acidBiochemistryHistone deacetylaseCombinatorial chemistryHistoneStereochemistryDNAHistone Deacetylase Inhibitors ResearchSynthetic Organic Chemistry MethodsPeptidase Inhibition and Analysis