Inhibition of Histone Demethylases by 4‐Carboxy‐2,2′‐Bipyridyl Compounds

Abstract

Exploiting epigenetics: 2-Oxoglutarate (2OG)-dependent histone lysine demethylases, such as JMJD2E, are potential therapeutic targets in a range of diseases. Through structure–activity relationship studies and analyses, we identified a potent 4-carboxy-2,2′-bipyridyl compound, which inhibits JMJD2E with an IC50 value of 110 nM, representing a 66-fold improvement over the lead compound. These bipyridyl derivatives bind in the 2-oxoglutarate binding site.