Use of the nitrile oxide cycloaddition (NOC) reaction for molecular probe generation: a new class of enzyme selective histone deacetylase inhibitors (HDACIs) showing picomolar activity at HDAC6.

Article Details

Citation

Kozikowski AP, Tapadar S, Luchini DN, Kim KH, Billadeau DD

Use of the nitrile oxide cycloaddition (NOC) reaction for molecular probe generation: a new class of enzyme selective histone deacetylase inhibitors (HDACIs) showing picomolar activity at HDAC6.

J Med Chem. 2008 Aug 14;51(15):4370-3. doi: 10.1021/jm8002894. Epub 2008 Jul 22.

PubMed ID
18642892 [ View in PubMed
]
Abstract

A series of hydroxamate based HDAC inhibitors containing a phenylisoxazole as the CAP group has been synthesized using nitrile oxide cycloaddition chemistry. An HDAC6 selective inhibitor having a potency of approximately 2 picomolar was identified. Some of the compounds were examined for their ability to block pancreatic cancer cell growth and found to be about 10-fold more potent than SAHA. This research provides valuable, new molecular probes for use in exploring HDAC biology.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
VorinostatHistone deacetylase 1IC 50 (nM)96N/AN/ADetails
VorinostatHistone deacetylase 2IC 50 (nM)282N/AN/ADetails
VorinostatHistone deacetylase 3IC 50 (nM)17N/AN/ADetails
VorinostatHistone deacetylase 6IC 50 (nM)14N/AN/ADetails