The structural requirements of histone deacetylase inhibitors: suberoylanilide hydroxamic acid analogs modified at the C6 position.

Article Details

Citation

Choi SE, Pflum MK

The structural requirements of histone deacetylase inhibitors: suberoylanilide hydroxamic acid analogs modified at the C6 position.

Bioorg Med Chem Lett. 2012 Dec 1;22(23):7084-6. doi: 10.1016/j.bmcl.2012.09.093. Epub 2012 Oct 2.

PubMed ID
23089527 [ View in PubMed
]
Abstract

Suberoylanilide hydroxamic acid (SAHA, Vorinostat), the first FDA-approved histone deacetylase (HDAC) inhibitor drug, was modified at the C6 position to study the structural requirements for high potency and selectivity. Substituents on the C6 position only modestly influenced inhibitor potency, with poorer activity observed as substituent size increased. Interestingly, C6 substituents also modestly influenced selectivity compared to the parent compound, SAHA. This systematic study documenting the influence of substituents on the SAHA linker region will aid development of anti-cancer drugs targeting HDAC proteins.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
VorinostatHistone deacetylase 1IC 50 (nM)96N/AN/ADetails
VorinostatHistone deacetylase 3IC 50 (nM)136N/AN/ADetails
VorinostatHistone deacetylase 6IC 50 (nM)74N/AN/ADetails