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

Alan P. Kozikowski; Subhasish Tapadar; Doris N. Luchini; Hwan Kim Ki; Daniel D. Billadeau

doi:10.1021/jm8002894

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

Alan P. Kozikowski, Subhasish Tapadar, Doris N. Luchini, Hwan Kim Ki, Daniel D. Billadeau

Research output: Contribution to journal › Article › peer-review

153 Scopus citations

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 ∼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.

Original language	English (US)
Pages (from-to)	4370-4373
Number of pages	4
Journal	Journal of medicinal chemistry
Volume	51
Issue number	15
DOIs	https://doi.org/10.1021/jm8002894
State	Published - Aug 14 2008
Externally published	Yes

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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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. / Kozikowski, Alan P.; Tapadar, Subhasish; Luchini, Doris N. et al.
In: Journal of medicinal chemistry, Vol. 51, No. 15, 14.08.2008, p. 4370-4373.

Research output: Contribution to journal › Article › peer-review

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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

Abstract

ASJC Scopus subject areas

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