EPZ004777 (formate)

EPZ004777 is a potent inhibitor of DOT1L (IC₅₀ = 400 pM) that selectively kills mixed lineage leukemia (MLL) cells in vitro and prolongs survival in an MLL xenograft mouse model.^1,2,3,4 It displays >1,000-fold selectivity for DOT1L relative to a panel of histone methyltransferases.¹ DOT1L inhibition by EPZ004777 has also been shown to accelerate the reprogramming of somatic cells into induced pluripotent stem cells.⁵

1.Daigle, S.R., Olhava, E.J., Therkelsen, C.A., et al.Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitorCancer Cell.20(1)53-65(2011) 2.Chen, L., Deshpande, A.J., Banka, D., et al.Abrogation of MLL-AF10 and CALM-AF10-mediated transformation through genetic inactivation or pharmacological inhibition of the H3K79 methyltransferase Dot1lLeukemia27(4)813-822(2013) 3.Deshpande, A.J., Chen, L., Fazio, M., et al.Leukemic transformation by the MLL-AF6 fusion oncogene requires the H3K79 methyltransferase Dot1lBlood121(13)2533-2541(2013) 4.Yu, W., Chory, E.J., Wernimont, A.K., et al.Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitorsNat. Commun.31288(2012) 5.Ye, J., Ge, J., Zhang, X., et al.Pluripotent stem cells induced from mouse neural stem cells and small intestinal epithelial cells by small molecule compoundsCell Res.26(1)34-45(2016)