E67-2, a derivative of E67, is a low-toxicity, selective inhibitor of the KIAA1718 Jumonji domain. It has an IC 50 value of 3.4 μM. E67-2 specifically inhibits the Jumonji demethylase for histone H3 lysine 9 (H3K9) and histone H3 lysine 4 (H3K4) demethylase.

H3K9 Jumonji demethylase:3.4 μM (IC50)

E67-2, at concentrations ranging from 1 to 100 μM and with a 5-minute exposure, significantly diminishes the inhibitory effect on GLP, achieving an IC 50 of 75 μM, which represents a reduction in inhibitory capacity by approximately 1500-fold. Additionally, the compound demonstrates a markedly decreased inhibition of PHF8 activity on the H3(1-24)K4me3K9me2 peptide substrate, which is doubly methylated. Furthermore, in fibroblast cultures treated with E67-2 at concentrations between 100 and 100,000 nM for 24 hours, there is a notable decrease in cell toxicity[1].