Table 2:

Focused SAR highlights the substitution of the PFB ring with TFB analogs showing improvements in selectivity for HDAC6. We have also shown that TFB analogs have superior metabolic profiles compared to their PFB isotypes. Substituent location on the cap group aromatic ring plays a significant role in targeted HDAC6 binding. The pyridine motifs displayed the most potent and discriminative activity against HDAC6. IC₅₀ values were determined as described in Table 1 caption and supplementary procedures. IC₅₀ values are an average of duplicate experiments and are reported in μM, and their 95% confidence interval is italicized and reported in brackets under each IC₅₀ value. Full IC₅₀ curves are shown in supplementary data.