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.
MeSH terms
-
Animals
-
Antineoplastic Agents / pharmacology
-
Cell Line, Tumor
-
Cell Survival / drug effects
-
Co-Repressor Proteins* / metabolism
-
Histone Deacetylase 1 / antagonists & inhibitors
-
Histone Deacetylase Inhibitors / chemistry
-
Histone Deacetylase Inhibitors / pharmacology
-
Histone Deacetylases* / metabolism
-
Histone Demethylases / antagonists & inhibitors
-
Humans
-
Mice
-
Proteolysis
Substances
-
Antineoplastic Agents
-
Co-Repressor Proteins
-
HDAC1 protein, human
-
Histone Deacetylase 1
-
Histone Deacetylase Inhibitors
-
Histone Deacetylases
-
Histone Demethylases
-
KDM1A protein, human