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Discovery of histone deacetylase 8 selective inhibitors.

ABSTRACT: We have developed an efficient method for synthesizing candidate histone deacetylase (HDAC) inhibitors in 96-well plates, which are used directly in high-throughput screening. We selected building blocks having hydrazide, aldehyde and hydroxamic acid functionalities. The hydrazides were coupled with different aldehydes in DMSO. The resulting products have the previously identified 'cap/linker/biasing element' structure known to favor inhibition of HDACs. These compounds were assayed without further purification. HDAC8-selective inhibitors were discovered from this novel collection of compounds.

SUBMITTER: Tang W

PROVIDER: S-EPMC3403710 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Discovery of histone deacetylase 8 selective inhibitors.

Tang Weiping W Luo Tuoping T Greenberg Edward F EF Bradner James E JE Schreiber Stuart L SL

Bioorganic & medicinal chemistry letters 20110202 9

We have developed an efficient method for synthesizing candidate histone deacetylase (HDAC) inhibitors in 96-well plates, which are used directly in high-throughput screening. We selected building blocks having hydrazide, aldehyde and hydroxamic acid functionalities. The hydrazides were coupled with different aldehydes in DMSO. The resulting products have the previously identified 'cap/linker/biasing element' structure known to favor inhibition of HDACs. These compounds were assayed without furt ...[more]

PMID: 21334896

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