PROTAC-mediated degradation of class I histone deacetylase enzymes in corepressor complexes
journal contributionposted on 10.07.2020, 15:15 by Joshua P Smalley, Grace E Adams, Christopher J Millard, Yun Song, James KS Norris, John WR Schwabe, Shaun Michael Cowley, James T Hodgkinson
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.