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METTL3 inhibitors target methyltransferase-like 3 (METTL3), the catalytic RNA methyltransferase subunit. METTL3 forms a heterodimer with methyltransferase-like 14 (METTL14), in which METTL3 binds the methyl donor S-adenosylmethionine (SAM). The complex deposits N6-methyladenosine (m6A), the most abundant internal modification of messenger RNA (mRNA). These m6A marks influence mRNA splicing, export, translation and decay through dedicated reader proteins. Selective inhibition of METTL3 slowed the growth of acute myeloid leukemia (AML) models, which drew wide interest to the enzyme. STM2457 and UZH2 bind the SAM pocket of METTL3, and STC-15 is a further METTL3 inhibitor. S-adenosylhomocysteine (SAH), the product of the methyl transfer reaction, is also listed. Readers and erasers of the mark have their own categories, YTHDF and FTO.
