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.
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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
Drug Target Property Measurement pH Temperature (°C) Vorinostat Histone deacetylase 1 IC 50 (nM) 96 N/A N/A Details Vorinostat Histone deacetylase 2 IC 50 (nM) 282 N/A N/A Details Vorinostat Histone deacetylase 3 IC 50 (nM) 17 N/A N/A Details Vorinostat Histone deacetylase 6 IC 50 (nM) 14 N/A N/A Details