Development of Novel PRMT7 Inhibitors for the Treatment of Prostate Cancer.

Prostate cancer (PCa) remains a prevalent malignancy in men and warrants novel and efficacious therapy. Protein arginine methyltransferase 7 (PRMT7) has been recently identified as a promising target for PCa treatment, however, the development of efficacious PRMT7 inhibitors is limited. Herein, we reported an effective and selective PRMT7 inhibitor, A33, which was obtained through structural optimization and exhibited potent anti-PCa efficacy in vitro and in vivo. A33 significantly inhibited the proliferation, colony formation, migration, and invasion of PCa cells and induced substantial cell cycle arrest and apoptosis. Mechanistically, A33 decreased the monomethylarginine level in PCa cells, regulated tumor metastasis-, proliferation-, and apoptosis-associated proteins, and enhanced antitumor innate immunity by targeting PRMT7. More importantly, A33 exhibited low toxicity and effectively suppressed PCa tumor growth in the DU-145 xenograft tumor model. Collectively, this study provides a novel potent PRMT7 inhibitor for further anti-PCa drug discovery.