Epigenetic modulators such as Lysine-specific Demethylase 1 (LSD1) and Histone Deacetylases (HDACs), are drug targets for cancer, neuropsychatric disease or inflammation but inhibitors of these enzymes exhibit considerable side effects. For a potential local treatment with reduced systemic toxicity, we present here soft drugs as new LSD1 and HDAC inhibitors. A soft drug is a compound that is degraded in vivo to less active metabolites, after having achieved its therapeutic function. This has been successfully applied for corticosteroids in the clinic but soft drugs targeting epigenetic enzymes are scarce, with the HDAC inhibitor remetinostat being the only example. We have developed new methyl ester containing inhibitors targeting LSD1 respectively HDACs and compared their biological activity to the one of their respective carboxylic acids cleavage products. In vitro activity assays, cellular experiments, and a stability assay identified potent HDAC and LSD1 soft drugs that are superior to their corresponding carboxylic acids as potential candidates for local therapy with minimized side effects.