作为RNA最常见的表观遗传调控形式,N6甲基腺苷(m6A)修饰与生理过程密切相关,比如成长和发展,干细胞更新和分化,和DNA损伤反应。同时,其在癌组织中的异常表达促进恶性肿瘤的发展,以及在扩散中发挥重要作用,转移,耐药性,免疫和预后。近年来,m6A与癌症之间的紧密联系引起了广泛关注。越来越多的小分子已经成为靶向m6A调节因子用于癌症治疗的潜在试剂。这些分子靶向表观遗传水平,能够精确干预RNA修饰并有效破坏肿瘤细胞的生存机制,从而为癌症治疗的新方法铺平了道路。然而,目前缺乏针对靶向m6A调节因子的小分子抗肿瘤的全面综述.这里,我们全面总结了M6A调节器的分类和功能,阐明它们与增殖的相互作用,转移,耐药性,和常见癌症的免疫反应。此外,我们提供了有关发展的全面概述,行动模式,靶向m6A调节剂的小分子的药理学和结构-活性关系。我们的目标是为后续药物设计和优化提供见解,同时也对靶向M6A的小分子开发的未来前景进行了展望。
As the most common form of epigenetic regulation by RNA, N6 methyladenosine (m6A) modification is closely involved in physiological processes, such as growth and development, stem cell renewal and differentiation, and DNA damage response. Meanwhile, its aberrant expression in cancer tissues promotes the development of malignant tumors, as well as plays important roles in proliferation, metastasis, drug resistance, immunity and prognosis. This close association between m6A and cancers has garnered substantial attention in recent years. An increasing number of small molecules have emerged as potential agents to target m6A regulators for cancer treatment. These molecules target the epigenetic level, enabling precise intervention in RNA modifications and efficiently disrupting the survival mechanisms of tumor cells, thus paving the way for novel approaches in cancer treatment. However, there is currently a lack of a comprehensive review on small molecules targeting m6A regulators for anti-tumor. Here, we have comprehensively summarized the classification and functions of m6A regulators, elucidating their interactions with the proliferation, metastasis, drug resistance, and immune responses in common cancers. Furthermore, we have provided a comprehensive overview on the development, mode of action, pharmacology and structure-activity relationships of small molecules targeting m6A regulators. Our aim is to offer insights for subsequent drug design and optimization, while also providing an outlook on future prospects for small molecule development targeting m6A.