EP102

EP102 is an orally active, selective inhibitor of the METTL3/METTL14 complex with an IC₅₀ of 2 nM. EP102 reduces intracellular N6-methyladenosine levels, inhibits cancer cell proliferation, and thereby suppresses tumor growth in mouse models. EP102 is applicable for the research of acute myeloid leukemia, ovarian solid tumors and advanced solid tumors ^[1].

In Vivo, EP102 (20-47 mg/kg; p.o.; QD, TIW; 4 weeks) inhibits AML tumor growth in a disseminated mouse xenograft model, with superior efficacy observed with a 47 mg/kg oral three-times-weekly dose compared to a 20 mg/kg oral daily dose^[1]. EP102 (47 mg/kg; p.o.; TIW; 32 days) achieves >90% tumor growth inhibition and reduces metastasis in an intraovarian mouse xenograft model of ovarian cancer when dosed orally at 47 mg/kg three times weekly^[1].

In Vitro, EP102 (72 h) inhibits the viability of Kasumi-1, MV-4-11, Calu-6, A549, FaDu, SK-OV-3, and Caov-3 human cancer cell lines with IC₅₀ values ranging from 31 nM to 225 nM^[1]. EP102 inhibits intracellular m6A levels in Kasumi-1, MV-4-11, Calu-6, A549, FaDu, and SK-OV-3 human cancer cell lines with IC₅₀ values ranging from 6 nM to 19 nM^[1]. EP102 exhibits metabolic stability in rat, minipig, and human liver microsomes with half-lives of 149 min, 44 min, and 53 min, respectively^[1]. EP102 selectively inhibits human CYP3A4 with an IC₅₀ of 0.9 μM and CYP3A5 with an IC₅₀ of 16 μM, while not significantly inhibiting the other 8 tested major human CYPs^[1].

References:
[1]. Dutheuil G, et al. Optimization of METTL3 Inhibitors for the Treatment of Solid Tumors and AML. J Med Chem. 2026;69(8):9585-9602.