However, because of the large differences between the anti-proliferation activity (EC50: 35-480 nM) and H3K27 methylation inhibition (IC50 >6 μM) for 4, our results supported that DOT1L/H3K79 methylation inhibition (with IC50 ~50 nM, Fig. 4b) is mainly responsible for the activity of compound 4 against these breast cancer cells. Here, DOT1L is linked to breast cancer.