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

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.