Recent progress of METTL3 inhibitors for cancer therapeutics: design, optimization and potential applications

Abstract

Acute myeloid leukaemia (AML) is a clonal proliferative malignant hematologic disease of hematopoietic stem cells, characterized by the accumulation of immature progenitor cells and the inhibition of hematopoietic function due to blocked differentiation, which is a genetically heterogeneous and dynamic disease and the most common type of leukemia in adults. Studies have shown that methyltransferase-like protein 3 (METTL3) is highly expressed in AML cells, regulating methylation modifications that drive the development of leukemia. This discovery has become a major breakthrough in the treatment of AML, as it is possible to address common issues in current chemotherapy, such as drug resistance, by developing METTL3 inhibitors. This review summarizes the strategies for discovering and optimizing the medicinal chemistry of METTL3 inhibitors, provides a reference for future drug development, and looks forward to the potential application prospects of METTL3 inhibitors in clinical practice.