EPZ-5676 is a highly potent and selective inhibitor of DOT1L methyltransferase with Ki of 70 pM, selectively blocking the binding of the cofactor, S-adenosylmethionine. It inhibits proliferation of MLL-AF4 rearranged cell line MV4-11 with an IC50 of 9 nM. It reduces H3K79 dimethylation with a cellular IC50 of 2.6 nM in MV4-11 cells. EPZ-5676 has over 10, 000-fold selectivity against other HMTs. Its superior potency is associated with its increased enzyme residence time and prolonged cellular effects after washout. It can reduce H3K79 methylation in all cells, but only kill cells with MLL rearrangement, making it a good drug candidate for cancer therapy. Now EPZ-5676 is in phase I clinical trials for advanced hematologic malignancies, including acute Leukemia with rearrangement of the MLL gene.
CAS Number: 1380288-87-8
Molecular Weight: 562.71
Chemical Name: (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol
Appearance: Solid Power.
Purity: ≥98% (or refer to the Certificate of Analysis)
Solubility: DMSO up to 50 mM
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis
Storage Condition: Dry, dark and -20 oC for 1 year or refer to the Certificate of Analysis.
Shelf Life: ≥12 months if stored properly.
Stock Solution Storage: 0 - 4 oC for 1 month or refer to the Certificate of Analysis.
Drug Formulation: To be determined.
HS Tariff Code: 382200
How to use
EPZ-5676 was used at 1 µM final concentration in vitro and in cellular assays.
Continuous intravenous infusion of EPZ-5676 at 70.5 mg/kg once per day for 21 days achieved complete tumor regressions in a nude rat subcutaneous xenograft model of MLL-rearranged leukemia.
- Roy M Pollock. Preclinical Characterization of a Potent, Selective Inhibitor of the Protein Methyltransferase DOT1L for Use in the Treatment of MLL-Rearranged Leukemia. (2012) 54th ASH Annual Meeting and Exposition.
- Robert A Copeland. Protein methyltransferases in cancer. (2013) AACR Annual Meeting.
Products are for research use only. Not for human use.
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