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

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.