Design, synthesis, and activity of HDAC inhibitors with a N-formyl hydroxylamine head group.

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Wu TY, Hassig C, Wu Y, Ding S, Schultz PG

Design, synthesis, and activity of HDAC inhibitors with a N-formyl hydroxylamine head group.

Bioorg Med Chem Lett. 2004 Jan 19;14(2):449-53.

PubMed ID
14698179 [ View in PubMed
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Abstract

Histone deacetylases (HDAC) are promising targets for cancer chemotherapy. HDAC inhibitors are thought to act in part by disrupting normal cell cycle regulation, resulting in apoptosis and/or differentiation of transformed cells. Several HDAC inhibitors, which contain hydrophobic tails and the Zn(2+) chelator hydroxyamic acid as a head group, are potent inhibitors of HDACs both in vitro and in vivo. In this study, a related class of compounds with a N-formyl hydroxylamino head group has been synthesized and their ability to inhibit HDACs have been assayed in biochemical and cellular assays. These compounds were found to have comparable activities to suberoylanilide hydroxyamic acid (SAHA) in HDAC enzymatic assays and histone hyperacetylation cellular assays.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
VorinostatHistone deacetylase 1IC 50 (nM)480N/AN/ADetails
VorinostatHistone deacetylase 2IC 50 (nM)73N/AN/ADetails
VorinostatHistone deacetylase 6IC 50 (nM)100N/AN/ADetails