药物化学策略在METTL3抑制剂研发领域的最新进展
Recent Advances in Medicinal Chemistry Strategies for the Development of METTL3 Inhibitors
DOI: 10.12677/hjmce.2026.141008, PDF,   
作者: 蔡江涛：浙江师范大学化学与材料科学学院，浙江 金华
关键词: METTL3；前列腺癌；STM2457；PROTAC；METTL3； Prostate Cancer； STM2457； PROTAC
摘要: METTL3作为m6A RNA甲基化的关键催化酶，在多种疾病特别是肿瘤的发生发展中扮演重要角色。其通过介导RNA的m6A修饰，动态调控靶基因的剪接、稳定性、翻译及降解，从而影响细胞增殖、分化、代谢及肿瘤进展等生物学过程。在多种癌症中，METTL3的表达异常与肿瘤的发生、侵袭、转移及治疗抵抗密切相关，其作用具有高度的环境与细胞类型依赖性。在前列腺癌中，METTL3的作用日益受到关注。研究表明，METTL3可通过m6A修饰直接或间接调控雄激素受体(AR)信号通路，影响前列腺癌的进展及去势抵抗性的形成。针对METTL3的小分子抑制剂研发正处于探索阶段，旨在通过阻断其甲基转移酶活性，扰乱致癌的m6A修饰谱，为克服前列腺癌(尤其是mCRPC)的治疗耐药提供新的策略。然而，鉴于m6A修饰在正常生理中的广泛作用，开发高选择性、低毒性的METTL3抑制剂仍是重大挑战。未来的研究需进一步阐明METTL3在前列腺癌中的精确底物与作用网络，并探索其作为生物标志物或治疗靶点的临床转化潜力。
Abstract: METTL3, as a key catalytic enzyme for m6A RNA methylation, plays a crucial role in the development of various diseases, particularly tumors. By mediating m6A modifications on RNA, it dynamically regulates the splicing, stability, translation, and degradation of target genes, thereby influencing biological processes such as cell proliferation, differentiation, metabolism, and tumor progression. In multiple cancers, abnormal METTL3 expression is closely associated with tumorigenesis, invasion, metastasis, and treatment resistance, exhibiting high environmental and cell type dependency. Its role in prostate cancer is gaining increasing attention. Studies indicate that METTL3 directly or indirectly regulates the Androgen Receptor (AR) signaling pathway via m6A modification, influencing prostate cancer progression and the development of castration resistance. The development of small-molecule METTL3 inhibitors is currently in the exploratory phase, aiming to disrupt oncogenic m6A modification profiles by blocking its methyltransferase activity, thereby offering novel strategies to overcome treatment resistance in prostate cancer (particularly mCRPC). However, given the extensive roles of m6A modifications in normal physiology, developing highly selective, low-toxicity METTL3 inhibitors remains a significant challenge. Future research should further elucidate the precise substrates and functional networks of METTL3 in prostate cancer and explore its clinical translational potential as a biomarker or therapeutic target.
文章引用：蔡江涛. 药物化学策略在METTL3抑制剂研发领域的最新进展[J]. 药物化学, 2026, 14(1): 76-88. https://doi.org/10.12677/hjmce.2026.141008

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