Carbamate Prodrug Concept for Hydroxamate HDAC Inhibitors

Virtual screening efforts have identified several novel HDAC6 inhibitors with cellular isoform selectivity. In particular, a carbamate-protected hydroxamic acid exhibited improved effects with respect to protein hyperacetylation compared with the parent hydroxamate, possibly because of improved cell permeability. The carbamate structure therefore represents a potential prodrug concept for hydroxamic acid-containing HDAC inhibitors.