METTL3-IN-11 is a highly selective METTL3 inhibitor (IC50 = 45.31 nM), demonstrating greater selectivity for METTL3 over DNMT1, EZH1, MLL1, and PRMT1. It reduces m6A levels in total RNA of MOLM-13 and SKOV3 cells, inducing apoptosis and inhibiting migration. METTL3-IN-11 also decreases expression of m6A downstream target genes (c-MYC and BCL2). It is applicable in ovarian cancer and acute myeloid leukemia research.

METTL3-IN-11 (Compound 30t) demonstrates significant antiproliferative activity in SKOV3 (IC 50 = 6.42 μM) and MOLM-13 (IC 50 = 12.34 μM) cells while exhibiting lower toxicity in LO2 and HK2 cells. At concentrations of 25 μM and 50 μM, HK2 cell viability is significantly higher than the positive control STM2457. METTL3-IN-11 (5-15 μM) reduces total RNA m6A levels in SKOV3 and MOLM-13 cells in a dose-dependent manner. Additionally, when administered at 10-25 μM for 48 hours, it markedly inhibits the migration of SKOV3 cells and induces apoptosis. Although METTL3-IN-11 (10-25 μM, 48 hours) does not affect the expression levels of the METTL3 protein, it downregulates the protein expression of m6A downstream target genes (such as c-MYC and BCL2) in SKOV3 and MOLM-13 cells in a dose-dependent fashion.

METTL3-IN-11 (Compound 30t), administered intraperitoneally at 50 mg/kg once daily for two weeks, significantly inhibits tumor growth in SKOV3 tumor-bearing mice while maintaining stable body weight and showing no evident toxic reactions.