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 journalArticle

137 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)4370-4373
Number of pages4
JournalJournal of Medicinal Chemistry
Volume51
Issue number15
DOIs
StatePublished - Aug 14 2008

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Molecular Probes
Nitriles
Histone Deacetylase Inhibitors
Cycloaddition
Cycloaddition Reaction
Cell growth
Pancreatic Neoplasms
Oxides
Enzymes
Growth
Research

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

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.; Ki, Hwan Kim; Billadeau, Daniel D.

In: Journal of Medicinal Chemistry, Vol. 51, No. 15, 14.08.2008, p. 4370-4373.

Research output: Contribution to journalArticle

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