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

Oncology

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

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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10.1021/jm8002894

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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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