Patent landscape of small molecule inhibitors of METTL3 (2020-present)

Methyltransferase-like protein 3 (METTL3), in complex with METTL14, is the key 'writer' protein for RNA m⁶A methylation, accounting for almost all mRNA m⁶A modifications. Recent studies reveal that METTL3 is implicated in the development and progression of various types of cancers. Targeting METTL3 with small molecule inhibitors represents a promising therapeutic strategy for cancer.

This review provides an overview of the patent literature covering METTL3 inhibitors. A literature search was conducted in SciFinder by using 'METTL3 inhibitor' as a keyword and was refined by narrowing the criteria to patents.

Efforts to develop METTL3/METTL14 inhibitors have led to the advancement of the drug candidate STC-15 to clinical trials. Preclinical studies of STC-15 show promise in inhibiting tumor growth via direct anti-tumor effects and anti-cancer immune responses. The clinical trial outcomes of STC-15 will shape future METTL3/METTL14 inhibitor development. However, critical questions remain. The role of METTL3/METTL14 in m⁶A RNA methylation is essential for cellular activity, raising concerns about the potential adverse effects of targeting this complex. Furthermore, depending on the context, METTL3/METTL14 can function as a tumor suppressor. This underscores the need for a deeper understanding of the molecular mechanisms by which RNA modifications regulate cancer.