1-Methyl-2-nitroimidazole has been identified as a good masking group for NTR substrates, which is characterized by fast unmasking, and it has been further used as a prodrug moiety for the cell-specific delivery of several chemotherapeutic agents . Recently, the NTRactivated prodrug approach has been successfully applied for the design of different epigenetic inhibitors, such as the hydroxamate-based HDACi vorinostat (SAHA) and the lysine-specific histone demethylase 1 (LSD1) tranylcypromine . In the present study we used this system to develop a research tool to study the effects of class I selective HDAC inhibitors in targeted cells which, as non-cytotoxic agents, also allow the study of the effect of the Michael acceptor that is formed upon enzymatic uncaging. We developed different nitroaryl-based NTR prodrugs for class I HDAC inhibitors using previously developed aminobenzamide based HDAC inhibitors. Furthermore, the biological activity of the newly synthesized prodrugs is evaluated against acute myeloid leukemia (AML) cells using an NTR enzyme-prodrug system.