PROTAC-mediated degradation of class I histone deacetylase enzymes in corepressor complexes.
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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Antiviral Agents, Cell Line, Tumor, Drug Design, Drug Resistance, Viral, Gene Knockdown Techniques, HEK293 Cells, Hepacivirus, Hepatitis C, Humans, Intracellular Signaling Peptides and Proteins, Ligands, Models, Molecular, Oligopeptides, Proof of Concept Study, Protease Inhibitors, Proteolysis, Ubiquitin-Protein Ligases, Viral Nonstructural Proteins
Adaptor Proteins, Signal Transducing, Antiviral Agents, Cell Line, Tumor, Drug Design, Drug Resistance, Viral, Gene Knockdown Techniques, HEK293 Cells, Hepacivirus, Hepatitis C, Humans, Intracellular Signaling Peptides and Proteins, Ligands, Models, Molecular, Oligopeptides, Proof of Concept Study, Protease Inhibitors, Proteolysis, Ubiquitin-Protein Ligases, Viral Nonstructural Proteins
Chem. Commun. (Camb.)
Date: Apr. 21, 2020
PubMed ID: 32201871
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