Pimelic Diphenylamide 106

Pimelic diphenylamide 106 is a slow, tight-binding inhibitor of class I histone deacetylases (HDACs).{16844} Unlike the HDAC inhibitor suberoylanilide hydroamic acid, which has a fast-on/fast-off HDAC binding rate, pimelic diphenylamide 106 progressively binds HDACs and remains bound after wash-out. As a result, the IC50 of pimelic diphenylamide 106 decreases over time. With prolonged preincubation (1-3 hours), pimelic diphenylamide inhibits the class I HDACs (IC50 = 150, 760, 370, and 5,000 nM for HDAC1, 2, 3, and 8, respectively) but not the class II HDACs (IC50 > 180 ?M for HDAC4, 5, and 7).{16844} Pimelic diphenylamide 106 and related benzamide HDAC inhibitors may have therapeutic value in Friedrich’s ataxia{16844,17391,17392} and Huntington’s disease,{17390} in part due to their low animal toxicity.