In an effort to search for potential small-molecule drugs targeting epigenetic modifiers including histone demethylases for CRC treatment, we identified GSK-J4, a potent cell-permeable inhibitor blocking the catalytic site of both KDM6A and KDM6B, effectively suppressed the proliferation of CRC cells from various origins (IC50 ranging from 0.75 μm to 21.41 μm with a median of 6.20 to 6.35 μm) according to data from PharmacoDB database 21 (Figure 1A). Here, KDM6B is linked to colorectal carcinoma.