Identification of protein arginine methyltransferase 7 (PRMT7) inhibitor by virtual screening and biological evaluation in vitro

Although protein arginine methyltransferase 7 (PRMT7) is an important mediator in various biological processes, its specific inhibitors remain to be identified. To identify novel inhibitors of PRMT7, we utilized high-throughput virtual screening of the ChemDiv database for novel PRMT7 inhibitors. Eight compounds were identified, and among them, compound V009-0749 exhibited potent anticancer activity against the HepG2 hepatocellular carcinoma cell line in a dose-dependent manner. It inhibited the activity of PRMT7 by decreasing the histone H4 Arg 3 symmetric dimethylation (H4R3me2s) modification level in the HepG2 and Hep3B carcinoma cell lines. Furthermore, compound V009-0749 led to HepG2 and Hep3B cell cycle G1 phase arrest and cell apoptosis. Molecular modeling studies also suggested that compound V009-0749 had strong affinity for the binding site of PRMT7 by forming six hydrogen bonds and significant hydrophobic interactions. Compound V009-0749 could serve as a lead compound targeting PRMT7 activity, and lay the foundation for investigating the role of PRMT7 in hepatocellular carcinoma and other diseases.