The structural requirements of histone deacetylase inhibitors: Suberoylanilide hydroxamic acid analogs modified at the C3 position display isoform selectivity.

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Choi SE, Weerasinghe SV, Pflum MK

The structural requirements of histone deacetylase inhibitors: Suberoylanilide hydroxamic acid analogs modified at the C3 position display isoform selectivity.

Bioorg Med Chem Lett. 2011 Oct 15;21(20):6139-42. doi: 10.1016/j.bmcl.2011.08.027. Epub 2011 Aug 12.

PubMed ID
21889343 [ View in PubMed
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Abstract

The FDA-approved drug suberoylanilide hydroxamic acid (SAHA, Vorinostat) was modified to improve its selectivity for a single histone deaetylase (HDAC) isoform. We show that attaching an ethyl group at the C3 position transforms SAHA from nonselective to an HDAC6-selective inhibitor. Theses results indicate that small structural changes in SAHA can significantly influence selectivity, which will lead future anti-cancer design efforts 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)146N/AN/ADetails
VorinostatHistone deacetylase 6IC 50 (nM)74N/AN/ADetails