A-395 is an inhibitor of the interaction between embryonic ectoderm development (EED) and histone H3 lysine 27 (H3K27) that binds to the EED subunit of polycomb repressor complex 2 (PRC2) and inhibits H3K27 methylation (Ki = 0.4 nM).1 It inhibits H3K27 di- and trimethylation in RD rhabdoid tumor cells (IC50s = 390 and 90 nM, respectively). In vivo, A-395 (200 mg/kg) reduces tumor volume and intratumor H3K27 trimethylation in a Pfeiffer diffuse large B cell lymphoma (DLBCL) mouse xenograft model.
|1. Hey, Y., Selvaraju, S., Curtin, M.L., et al. The EED protein-protein interaction inhibitor A-395 inactivates the PRC2 complex. Nat. Chem. Biol. 13(4), 389-395 (2017).