EPZ004777, DOT1L inhibitor

EPZ004777 is a potent, selective inhibitor of DOT1L. Treatment of mixed lineage leukemia (MLL) cells with EPZ004777 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.

Product information

CAS Number: 1338466-77-5

Molecular Weight: 539.67

Formula: C28H41N7O4

Synonym:

EPZ 004777

EPZ-004777

Related CAS Number:

1380316-03-9 (HCl)

Chemical Name: 3-[3-({[(2R,3S,4R,5R)-5-{4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-3,4-dihydroxyoxolan-2-yl]methyl}(propan-2-yl)amino)propyl]-1-(4-tert-butylphenyl)urea

Smiles: CC(C)N(C[C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C=CC2=C1N=CN=C2N)CCCNC(=O)NC1C=CC(=CC=1)C(C)(C)C

InChiKey: WXRGFPHDRFQODR-ICLZECGLSA-N

InChi: InChI=1S/C28H41N7O4/c1-17(2)34(13-6-12-30-27(38)33-19-9-7-18(8-10-19)28(3,4)5)15-21-22(36)23(37)26(39-21)35-14-11-20-24(29)31-16-32-25(20)35/h7-11,14,16-17,21-23,26,36-37H,6,12-13,15H2,1-5H3,(H2,29,31,32)(H2,30,33,38)/t21-,22-,23-,26-/m1/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Solubility (25°C) DMSO: 100 mg/mL(185.29 mM). Water: Insoluble.

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: ≥360 days 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

In Vitro:

EPZ004777 selectively inhibits cellular H3K79 methylation and inhibits expression of key MLL fusion target genes. Following DOT1L inhibition, EPZ004777 selectively inhibits proliferation of MLL-Rearranged cell lines and MLL-AF9-transformed murine hematopoietic cells. In addition, EPZ004777 also induces differentiation and apoptosis in MLL-rearranged cells. EPZ004777 selectively inhibits proliferation of MLL–AF10 and CALM–AF10-transformed murine bone marrow cells. DOT1L inhibition by EPZ004777 results in significantly decreased proliferation, decreased expression of MLL-AF6 target genes, and cell cycle arrest of MLL-AF6-transformed cells.

In Vivo:

EPZ004777 produces potent antitumor efficacy, and significantly increases median survival in a mouse xenograft model of MLL leukemia.

References:

1. Deshpande AJ, et al. Blood. 2013, 121(13), 2533-2541.
2. Chen L, et al. Leukemia. 2013, 27(4), 813-822.
3. Daigle SR, et al. Cancer Cell. 2011, 20(1), 53-65.

Products are for research use only. Not for human use.