2. Academic Validation
  3. Development of Novel PRMT7 Inhibitors for the Treatment of Prostate Cancer

Development of Novel PRMT7 Inhibitors for the Treatment of Prostate Cancer

  • J Med Chem. 2025 Apr 24;68(8):8244-8268. doi: 10.1021/acs.jmedchem.4c02978.
Jiaxing Li 1 2,  Chengliang Sun 1 2,  Ying Zhang 1 2,  Jiayu Ding 1 2,  Peng Yao 1 2,  Hao Shen 1 2,  Zhongrui Shi 1 2,  Wenmu Wang 1 2,  Yasheng Zhu 1 2,  Wenbin Kuang 1 2,  Annayeva Tavus 1 2,  Liping Wang 1 2,  Kai Yuan 1 2,  Xiao Wang 1 2 3,  Peng Yang 1 2 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
  • 2 Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
  • 3 Institute of Innovative Drug Discovery and Development, China Pharmaceutical University, Nanjing 211198, China.
PMID: 40223545 DOI: 10.1021/acs.jmedchem.4c02978
Abstract

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.

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