@article{HU2025, 
author = {Zheqi HU and Chunxiang YIN and Huihuan MAO and Yiqing CHANG and Qihua ZHU and Yungen XU and Guoqing GONG and Yi ZOU},
title = {Research progress on second-generation protein arginine methyltransferase 5 inhibitors},
year = {2025},
journal = {Journal of China Pharmaceutical University},
volume = {56},
number = {5},
pages = {548-556},
keywords = {protein arginine methyltransferase 5, methioadenosine phosphorylase, methylthioadenosine, synthetic lethal},
url = {https://www.sciopen.com/article/10.11665/j.issn.1000-5048.2025021201},
doi = {10.11665/j.issn.1000-5048.2025021201},
abstract = {Protein arginine methyltransferase 5 (PRMT5) exhibits elevated expression levels in a variety of cancers and has emerged as a critical target for cancer therapy in recent years. However, first-generation PRMT5 inhibitors have exhibited inadequate selectivity, leading to significant hematological toxicity, thus limiting their clinical utility. The second-generation PRMT5 inhibitors have shown marked improvement in safety and efficacy by selectively targeting MTAP-null tumor cells without impacting normal cells. This review systematically summarizes the biological and functional roles of PRMT5 in MTAP-deficient tumor cells, and comprehensively analyzes the research and development process, molecular binding mechanisms, and the latest advancements in clinical trials of the five second-generation PRMT5 inhibitors currently under investigation, aiming to provide valuable insights for further in-depth studies in this field.}
}