CPI-455

CPI-455 is a potent and selective KDM5A inhibitor (IC₅₀ ~10 nM). It inhibits KDM5A, KDM5B and KDM5C to similar extents but shows substantially weaker potency toward KDM4C and KDM7B (~200- and 770-fold, respectively) and no detectable inhibition of KDM2B, KDM3B or KDM6A. It specifically alters H3K4 methylation in cells and binds at the demethylase active site. CPI-455-mediated KDM5 inhibition leads to a dose-dependent increase in global H3K4me3 in HeLa cells, and the removal of CPI-455 resulted in a rapid reversal of H3K4me3 increases in HeLa cells.