Highly potent and selective H3K4 demethylase KDM5A (JARID1A) inhibitor that improves iPSC reprogramming efficiency of human fibroblasts via OCT4 induction.

O4I3 is a highly potent and KDM5A (JARID1A) subtype-selective H3K4 demethylase KDM5 inhibitor (KDM5A IC₅₀ = 0.15 nM vs KDM5B/C/D IC₅₀ = 125.2/9.76/4.7 nM, KDM4 IC₅₀ = 249 nM, LSD1 IC₅₀ >100 μM) that effectively induces OCT4 expresson and improves OSKM-induced pluripotent stem cell (iPSC) reprogramming efficiency of human primary fibroblasts (50 nM) by preventing KDM5A from interfering with H3K4Me3 enrichment at the OCT4 promoter. O4I3 promotes hPSC homeostasis and represses cellular differentiation, increasing hPSCs viability up to 4-fold at a low 10 nM concentration when compared with Rock inhibitor Y-27632 treatment at 10 μM.