Potent and selective inhibition of histone deacetylase 6 (HDAC6) does not require a surface-binding motif.

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Wagner FF, Olson DE, Gale JP, Kaya T, Weiwer M, Aidoud N, Thomas M, Davoine EL, Lemercier BC, Zhang YL, Holson EB

Potent and selective inhibition of histone deacetylase 6 (HDAC6) does not require a surface-binding motif.

J Med Chem. 2013 Feb 28;56(4):1772-6. doi: 10.1021/jm301355j. Epub 2013 Feb 18.

PubMed ID
23368884 [ View in PubMed
]
Abstract

Hydroxamic acids were designed, synthesized, and evaluated for their ability to selectively inhibit human histone deacetylase 6 (HDAC6). Several inhibitors, including compound 14 (BRD9757), exhibited excellent potency and selectivity despite the absence of a surface-binding motif. The binding of these highly efficient ligands for HDAC6 is rationalized via structure-activity relationships. These results demonstrate that high selectivity and potent inhibition of HDAC6 can be achieved through careful choice of linker element only.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
VorinostatHistone deacetylase 1IC 50 (nM)4N/AN/ADetails
VorinostatHistone deacetylase 2IC 50 (nM)11N/AN/ADetails
VorinostatHistone deacetylase 3IC 50 (nM)3N/AN/ADetails
VorinostatHistone deacetylase 6IC 50 (nM)2N/AN/ADetails