Assessing Efficacy of HDAC Inhibitors

For irradiation, a Cs-137 source (Gammacell 3000; Nordion, Ottawa, ON, Canada) was used. Vorinostat and entinostat were obtained from Sigma Aldrich GmbH (Taufkirchen, Germany). The compound library of hydroxamic acid- and benzamide-type HDACi derivatives was provided by T. Kurz and F. K. Hansen (Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Duesseldorf, Düsseldorf, Germany). Synthesis and biological activities of the HDAC inhibitory compounds KSK64 [30 (link)] and DDK137 [79 (link)] were already described. More detailed information regarding the synthesis of the various HDACi is also provided by Pflieger et al. [80 (link)], Mackwitz et al. [81 (link)], and Krieger et al. [82 (link)]. Chemical structures of the HDACi tested are summarized in Supplementary Figure S1. HDAC inhibitory activity of the compounds was confirmed by analyses of hyperacetylation of histones as concluded from enzyme assays and cellular HDAC pan assays [20 (link),30 (link),33 (link),79 (link),82 (link)].