Figure 1.

In vitro profiling of HDAC6is. Panel (A) Formulas of compounds tested in this study. Five currently used inhibitors are considered HDAC6-specific, TSA as a control pan-specific HDAC inhibitor, and compound 6 synthesized specifically for this comparison. Compound 7 is an analog of 6 having an oxadiazole zinc-binding group (ZBG), as compared to remaining inhibitors that utilize a hydroxamate ZBG. Panel (B) Purified recombinant human HDACs were used to determine the potency of studied inhibitors in activity assays in vitro. IC₅₀ values were calculated from fitted data and plotted in the color-coded table. For exact underlying values, refer to Supplementary Materials Table S2. While hydroxamate-based compounds show off-target inhibition (primarily against HDAC10), the oxadiazole-based compound 7 is highly selective for HDAC6.