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Chem Commun (Camb). 2020 Mar 23. doi: 10.1039/d0cc01485k. [Epub ahead of print]

PROTAC-mediated degradation of class I histone deacetylase enzymes in corepressor complexes.

Author information

1
Leicester Institute of Structural and Chemical Biology and Department of Chemistry, University of Leicester, University Road, Leicester, LE1 7RH, UK. JTHodgkinson@le.ac.uk.
2
Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 9HN, UK. smc57@leicester.ac.uk.
3
Leicester Institute of Structural and Chemical Biology and Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 9HN, UK. john.schwabe@le.ac.uk.

Abstract

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.

PMID:
32201871
DOI:
10.1039/d0cc01485k

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