Effect of Inhibiting Histone Deacetylase with Short-Chain Carboxylic Acids and Their Hydroxamic Acid Analogs on Vertebrate Development and Neuronal Chromatin.

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Fass DM, Shah R, Ghosh B, Hennig K, Norton S, Zhao WN, Reis SA, Klein PS, Mazitschek R, Maglathlin RL, Lewis TA, Haggarty SJ

Effect of Inhibiting Histone Deacetylase with Short-Chain Carboxylic Acids and Their Hydroxamic Acid Analogs on Vertebrate Development and Neuronal Chromatin.

ACS Med Chem Lett. 2010 Oct 8;2(1):39-42.

PubMed ID
21874153 [ View in PubMed
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Abstract

Carboxylic acids with known central nervous system and histone deacetylase (HDAC) inhibitory activities were converted to hydroxamic acids and tested using a suite of in vitro biochemical assays with recombinant HDAC isoforms, cell based assays in human cervical carcinoma Hela cells and primary cultures from mouse forebrain, and a whole animal (Xenopus laevis) developmental assay. Relative to the parent carboxylic acids, two of these analogs exhibited enhanced potency, and one analog showed altered HDAC isoform selectivity and in vivo activity in the Xenopus assay. We discuss potential uses of these novel hydroxamic acids in studies aimed at determining the utility of HDAC inhibitors as memory enhancers and mood stabilizers.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
Valproic acidHistone deacetylase 2IC 50 (nM)62000N/AN/ADetails
Valproic acidHistone deacetylase 9IC 50 (nM)>2000000N/AN/ADetails