PROTAC-mediated degradation of class I histone deacetylase enzymes in corepressor complexes.
Joshua P SmalleyGrace E AdamsChristopher J MillardYun SongJames K S NorrisJohn W R SchwabeShaun Michael CowleyJames T HodgkinsonPublished in: Chemical communications (Cambridge, England) (2020)
We have identified a proteolysis targeting chimera (PROTAC) of class I HDACs 1, 2 and 3. The most active degrader consists of a benzamide HDAC inhibitor, an alkyl linker, and the von Hippel-Lindau E3 ligand. Our PROTAC increased histone acetylation levels and compromised colon cancer HCT116 cell viability, establishing a degradation strategy as an alternative to class I HDAC inhibition.