Li Jiaxing, Sun Chengliang, Zhang Ying, Ding Jiayu, Yao Peng, Shen Hao, Shi Zhongrui, Wang Wenmu, Zhu Yasheng, Kuang Wenbin, Tavus Annayeva, Wang Liping, Yuan Kai, Wang Xiao, Yang Peng
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
J Med Chem. 2025 Apr 24;68(8):8244-8268. doi: 10.1021/acs.jmedchem.4c02978. Epub 2025 Apr 14.
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, , which was obtained through structural optimization and exhibited potent anti-PCa efficacy in vitro and in vivo. significantly inhibited the proliferation, colony formation, migration, and invasion of PCa cells and induced substantial cell cycle arrest and apoptosis. Mechanistically, 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, 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.
前列腺癌（PCa）仍是男性中一种常见的恶性肿瘤，需要新的有效治疗方法。蛋白质精氨酸甲基转移酶7（PRMT7）最近被确定为前列腺癌治疗的一个有前景的靶点，然而，有效的PRMT7抑制剂的开发却很有限。在此，我们报道了一种有效且具有选择性的PRMT7抑制剂， ，它是通过结构优化获得的，在体外和体内均表现出强大的抗前列腺癌疗效。 显著抑制前列腺癌细胞的增殖、集落形成、迁移和侵袭，并诱导大量细胞周期停滞和凋亡。从机制上讲， 降低了前列腺癌细胞中的单甲基精氨酸水平，调节了与肿瘤转移、增殖和凋亡相关的蛋白质，并通过靶向PRMT7增强了抗肿瘤固有免疫。更重要的是， 在DU-145异种移植肿瘤模型中表现出低毒性，并有效抑制了前列腺癌肿瘤的生长。总的来说，这项研究为进一步发现抗前列腺癌药物提供了一种新型强效PRMT7抑制剂。
