Histone deacetylase inhibitors with a primary amide zinc binding group display antitumor activity in xenograft model.

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Attenni B, Ontoria JM, Cruz JC, Rowley M, Schultz-Fademrecht C, Steinkuhler C, Jones P

Histone deacetylase inhibitors with a primary amide zinc binding group display antitumor activity in xenograft model.

Bioorg Med Chem Lett. 2009 Jun 1;19(11):3081-4. doi: 10.1016/j.bmcl.2009.04.011. Epub 2009 Apr 9.

PubMed ID
19410459 [ View in PubMed
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Abstract

Histone deacetylase (HDAC) inhibition causes hyperacetylation of histones leading to differentiation, growth arrest and apoptosis of malignant cells, representing a new strategy in cancer therapy. Many of the known HDAC inhibitors (HDACi) that are in clinical trials possess a hydroxamic acid, that is a strong Zn(2+) binding group, thereby inhibiting some of the class I and class II isoforms. Herein we describe the identification of a selective class I HDAC inhibitor bearing a primary carboxamide moiety as zinc binding group. This HDACi displays good antiproliferative activity against multiple cancer cell lines, and demonstrates efficacy in a xenograft model comparable to vorinostat.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
VorinostatHistone deacetylase 2IC 50 (nM)82N/AN/ADetails
VorinostatHistone deacetylase 3IC 50 (nM)57N/AN/ADetails
VorinostatHistone deacetylase 6IC 50 (nM)43N/AN/ADetails