Design and synthesis of novel histone deacetylase inhibitor derived from nuclear localization signal peptide.

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Canzoneri JC, Chen PC, Oyelere AK

Design and synthesis of novel histone deacetylase inhibitor derived from nuclear localization signal peptide.

Bioorg Med Chem Lett. 2009 Dec 1;19(23):6588-90. doi: 10.1016/j.bmcl.2009.10.028. Epub 2009 Oct 13.

PubMed ID

19854643 [ View in PubMed

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Abstract

We describe herein the synthesis and characterization of a new class of histone deacetylase (HDAC) inhibitors derived from conjugation of a suberoylanilide hydroxamic acid-like aliphatic-hydroxamate pharmacophore to a nuclear localization signal peptide. We found that these conjugates inhibited the histone deacetylase activities of HDACs 1, 2, 6, and 8 in a manner similar to suberoylanilide hydroxamic acid (SAHA). Notably, compound 7b showed a threefold improvement in HDAC 1/2 inhibition, a threefold increase in HDAC 6 selectivity and a twofold increase in HDAC 8 selectivity when compared to SAHA.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Vorinostat	Histone deacetylase 6	IC 50 (nM)	800	N/A	N/A	Details