Histone-lysine N-methyltransferase SET7 emerged as a potential target for multiple cancers. In a virtual screening program used to explore new and potent inhibitors of SET7, compound 16 was discovered as a top hit with an IC<sub>50</sub> value of 6.02 μM. A further similarity search afforded a new compound 23, which exhibited better activity against SET7 with an IC<sub>50</sub> value of 1.96 μM. Importantly, compound 23 selectively inhibited the proliferation of MV4-11 cells. Comprehensively, compound 23 can serve as a lead for further identification and development of more potent SET7 inhibitors.