Small-MoleculeInhibitors Targeting RNA m6A Modifiers for Cancer Therapeutics:Latest Advances and Future Perspectives

作者：Hairong Tang, Ruijia Zhang, Ao Zhang · 发表于：Journal of Medicinal Chemistry · 年份：2025 · DOI：10.1021/acs.jmedchem.5c01570 · 被引用次数：17 · 研究领域：RNA modifications and cancer、Cancer-related gene regulation、RNA Research and Splicing

Abstract As the most prevalent post-translational modification in eukaryotic RNA, N6-methyladenosine (m6A) modification is involved in RNA metabolism and protein expression and plays critical roles in various physiological and pathological processes, especially in cancer. Dysregulated m6A modifications caused by aberrant expression of m6A modifiers are closely associated with cancer initiation, progression, metastasis, metabolism, and immune evasion. Recently, the first-in-class METTL3 inhibitor STC-15 has been approved for a phase 1b/2 clinical study in cancer patients, rendering the pharmacological inhibition of dysregulated oncogenic m6A modifying proteins with small-molecule inhibitors a novel and effective cancer therapeutic strategy. In this perspective, we provide the latest advances in small molecular inhibitors targeting oncogenic m6A modifying proteins. Furthermore, limitations, challenges, and future development in the field of RNA m6A epigenetic drug discovery are discussed.