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Ref Type Journal Article
PMID (21741596)
Authors Daigle SR, Olhava EJ, Therkelsen CA, Majer CR, Sneeringer CJ, Song J, Johnston LD, Scott MP, Smith JJ, Xiao Y, Jin L, Kuntz KW, Chesworth R, Moyer MP, Bernt KM, Tseng JC, Kung AL, Armstrong SA, Copeland RA, Richon VM, Pollock RM
Title Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor.
Journal Vol Issue Date Pages Journal Short Title
Cancer cell 20 1 2011 Jul 12 53-65 Cancer Cell
URL
Abstract Text Mislocated enzymatic activity of DOT1L has been proposed as a driver of leukemogenesis in mixed lineage leukemia (MLL). The characterization of EPZ004777, a potent, selective inhibitor of DOT1L is reported. Treatment of MLL cells with the compound selectively inhibits H3K79 methylation and blocks expression of leukemogenic genes. Exposure of leukemic cells to EPZ004777 results in selective killing of those cells bearing the MLL gene translocation, with little effect on non-MLL-translocated cells. Finally, in vivo administration of EPZ004777 leads to extension of survival in a mouse MLL xenograft model. These results provide compelling support for DOT1L inhibition as a basis for targeted therapeutics against MLL.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
EPZ004777 EPZ004777 0 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
EPZ004777 EPZ4777|EPZ-004777|EPZ 004777 DOT1L Inhibitor 3 EPZ004777 is a small molecule that inhibits DOT1L, which results in decreased histone H3 lysine 79 dimethylation, and potentially leads to decreased tumor cell proliferation (PMID: 21741596, PMID: 27535106, PMID: 31888761).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References