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.5WARNING This product is not for human or veterinary use.

[1] R. POLLOCK. Selective Killing of Mixed Lineage Leukemia Cells by a Potent Small-Molecule DOT1L Inhibitor[J]. Blood, 2010, 116 1: 780-780. DOI: 10.1182/blood.v116.21.780.780
[2] LIYING CHEN. Abrogation of MLL-AF10 and CALM-AF10 Mediated Transformation Through Genetic Inactivation or Pharmacological Inhibition of the H3K79 Methyltransferase DOT1L.[J]. Blood, 2012, 120 1: 2384-2384. DOI: 10.1182/blood.v120.21.2384.2384
[3] ANIRUDDHA J DESHPANDE. Leukemic transformation by the MLL-AF6 fusion oncogene requires the H3K79 methyltransferase Dot1l.[J]. Blood, 2013, 121 13: 2533-2541. DOI: 10.1182/blood-2012-11-465120
[4] WENYU YU. Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitors.[J]. Nature Communications, 2012: 1288. DOI: 10.1038/ncomms2304
[5] JUNQING YE. Pluripotent stem cells induced from mouse neural stem cells and small intestinal epithelial cells by small molecule compounds[J]. Cell Research, 2015, 26 1: 34-45. DOI: 10.1038/cr.2015.142