EPZ004777 Hydrochloride

EPZ004777 is a potent and selective inhibitor of DOT1L, a protein methyltransferase catalyzing the methylation of lysine 4 of histone H3 (H3K4), with the half maximal inhibition concentration IC50 value of 400 pM. EPZ004777 has been found to concentration-dependently inhibit the H3K79 methylation in a variety of mixed lineage leukemia (MLL) cells, including MLL-rearranged acute myeloid leukemia (MOLM-13 and MLL-AF9), MLL-rearranged biphenotypic leukemia (MV4-11 and MLL-AF4) and non-MLL-rearranged T cell acute leukemia cells. Additionally, EPZ004777 exhibits anti-proliferative activity against both MLL-rearranged and non-rearranged human leukemia cell lines, including RS4;11 (IC50: 6.47 μM), SEM (IC50: 1.72 μM), MV4-11 (IC50: 0.17 μM), THP-1 (IC50: 3.36 μM), MOLM-13 (IC50: 0.72 μM), KOPN-8 (IC50: 0.62 μM), REH (IC50: 13.9 μM), Kasumi-1 (IC50: 32.99 μM) and 697 (IC50: 36.57 μM).

Product information

CAS Number: 1380316-03-9

Molecular Weight: 576.13

Formula: C28H42ClN7O4

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 hydrochloride

Smiles: Cl.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: NPEPLDAFAVXSBD-XRJUUMFPSA-N

InChi: InChI=1S/C28H41N7O4.ClH/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);1H/t21-,22-,23-,26-;/m1./s1

Technical Data

Appearance: Solid Power

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

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

References:

1. 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. Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor. Cancer Cell. 2011 Jul 12;20(1):53-65. doi: 10.1016/j.ccr.2011.06.009.

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