EP652 is a potent, selective and in vivo active inhibitor of RNA methyltransferase METTL3 with IC50 of 2 nM (METTL3/14) in SPA primary assays.
EP652 dispalys high selectivity (at 10 μM) against a panel of 40 methyltransferases, as well as in a standard safety screen panel (44 targets, including GPCRs, ion channels, and kinases).
EP652 exhibits m6A inhibition in mRNA from Calu-6 after 24 h treatment with IC50 of 8.6 nM.
EP652 demonstrates potent efficacy in cellulo across various cell lines in Kasumi-1 and MV-4–11 (AML cell lines), Caov-3 and SK-OV-3 (ovarian cancer cell lines), Calu-6 and A549 (lung cancer cell lines), and FaDu (Head and neck cancer cell line)) in cell viability experiments.
EP652 demonstrates dose-dependent decrease of the m6A cellular level in PBMC from rates, maximum m6A reduction (∼75%) at as low as 0.3 mg/kg.
EP652 (10 and 30 mg/kg ip, QD) effectively arrested cancer progression in MV-4-11 model (MV-4-11-Luc-mCh-Puro CDX model).