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, <b>A33</b>, which was obtained through structural optimization and exhibited potent anti-PCa efficacy in vitro and in vivo. <b>A33</b> significantly inhibited the proliferation, colony formation, migration, and invasion of PCa cells and induced substantial cell cycle arrest and apoptosis. Mechanistically, <b>A33</b> 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, <b>A33</b> 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.
Authors
- Wenbin Kuang
- Wenmu Wang
- Jiayu Ding (ORCID: https://orcid.org/0000-0001-9264-218X)
- Zhongrui Shi (ORCID: https://orcid.org/0000-0001-7630-3268)
- Peng Yang (ORCID: https://orcid.org/0000-0002-2613-941X)
- Kai Yuan (ORCID: https://orcid.org/0000-0002-3030-6460)
- Ying Zhang (ORCID: https://orcid.org/0000-0001-9804-2986)
- Liping Wang (ORCID: https://orcid.org/0000-0002-9282-2751)
- Jiaxing Li (ORCID: https://orcid.org/0000-0001-5550-9259)
- Hao Shen (ORCID: https://orcid.org/0000-0003-3994-6680)
- Xiao Wang (ORCID: https://orcid.org/0000-0002-6217-4941)
- Yao Peng (ORCID: https://orcid.org/0000-0001-8992-8814)
- Yasheng Zhu (ORCID: https://orcid.org/0000-0002-1397-2517)
- Chengliang Sun (ORCID: https://orcid.org/0000-0002-8428-0091)
- Annayeva Tavus
Institutions
- China Pharmaceutical University (CN)
- Medicina (PL)
- State Key Laboratory of Natural Medicine
Publication Details
- Journal
- Journal of Medicinal Chemistry
- Published
- 2025-04-14
- DOI
- https://doi.org/10.1021/acs.jmedchem.4c02978
- Citations
- 2
- Primary Topic
- Cancer-related gene regulation
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Jiangsu Province
- National Key Research and Development Program of China
- Fundamental Research Funds for the Central Universities