Xinyue Wang, Xuetao Chen, Shuai Wen, Yi Mou, Xiaoke Guo, Zhengyu Jiang
N 6 -methyladenosine (m 6 A) represents the most abundant and functionally significant RNA modification implicated in epigenetic regulation, significantly impacting gene expression through the selective recognition by m 6 A reader proteins. Aberrant expression of m 6 A readers has been associated with cancer progression, contributing to tumor growth, metastasis, drug resistance, and immune evasion. With the increasing research on m 6 A readers, the discovery of small-molecule inhibitors targeting these proteins has emerged as a promising avenue for cancer therapy. This review delineates the classification and functional roles of m 6 A readers across various cancers. Furthermore, we summarize and discuss the recent progress in the development of small-molecule inhibitors, with a focus on the medicinal chemistry perspectives. We hope to provide valuable insights to guide future efforts in drug discovery and rational design targeting m 6 A readers for innovative cancer therapeutics. This review describes the structure and biological functions of m 6 A readers and summarizes the latest research on m 6 A readers, discussing recent advances in small molecule inhibitors of m 6 A readers from a medicinal chemistry perspective.