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| 2mg |
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| 25mg |
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Purity: ≥98%
Description: EPZ004777 (EPZ-004777) is a potent and selective inhibitor of DOT1 Like Histone Lysine Methyltransferase (DOT1L) inhibitor with antineoplastic activity. It inhibits DOT1L with an IC50 of 0.4 nM in a cell-free assay. It shows potent in vitro antiproliferative activity and high in vivo antitumor efficacy. Exposure of leukemic cells to EPZ 004777 laed to selective killing of cells bearing MLL gene translocation, with little effect on non-MLL-translocated cells. In addition, EPZ004777 extended the survival of mice bearing a MLL xenograft model.
| ln Vitro |
EPZ004777 shows a strong, concentration-dependent inhibition of 400±100 pM of DOT1L enzyme activity. When compared to other HMTs (PRMT5, 521±137 nM; others, >50 μM), EPZ004777 shows a notable degree of selectivity for DOT1L inhibition. The effects of prolonged EPZ004777 therapy were notably unique to cell lines having MLL rearrangements. While Jurkat cell proliferation remained unaffected, EPZ004777 dramatically decreased the number of viable MV4-11 and MOLM-13 cells. While MV4-11 cells in the presence of EPZ004777 continued to divide, a small population of these cells remained viable; yet, when tracking their growth curve over time, their numbers remained constant. MLL-AF9 transformed cells are substantially inhibited from proliferating when exposed to doses of EPZ004777 of 3 μM or above [1]. MLL-AF10 and CALM-AF10-transformed mouse bone marrow cells are selectively inhibited from proliferating by EPZ004777 [2].
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| ln Vivo |
There is no obvious toxicity seen with EPZ004777, and it is well tolerated. Following a continuous 14-day exposure to EPZ004777, a complete blood count study demonstrated a statistically significant rise in the total white blood cell count, attributed to an increase in neutrophils, monocytes, and lymphocytes. Administration of EPZ004777 (50, 100, or 150 mg/mL) is well tolerated, and no appreciable weight loss is seen[1].
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| Animal Protocol |
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| References |
[1]. Daigle SR, et al. Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor. Cancer Cell. 2011 Jul 12;20(1):53-65.
[2]. Chen L, et al. Abrogation of MLL-AF10 and CALM-AF10-mediated transformation through genetic inactivation or pharmacological inhibition of the H3K79 methyltransferase Dot1l. Leukemia. 2013 Apr;27(4):813-22 |
| Molecular Formula |
C28H41N7O4
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| Molecular Weight |
539.67
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| CAS # |
1338466-77-5
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| Related CAS # |
EPZ004777 hydrochloride;1380316-03-9
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| SMILES |
O1[C@]([H])([C@@]([H])([C@@]([H])([C@@]1([H])C([H])([H])N(C([H])([H])C([H])([H])C([H])([H])N([H])C(N([H])C1C([H])=C([H])C(=C([H])C=1[H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])=O)C([H])(C([H])([H])[H])C([H])([H])[H])O[H])O[H])N1C([H])=C([H])C2=C(N([H])[H])N=C([H])N=C12
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| InChi Key |
WXRGFPHDRFQODR-ICLZECGLSA-N
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| InChi Code |
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
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| Chemical Name |
1-(3-((((2R,3S,4R,5R)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl)(isopropyl)amino)propyl)-3-(4-(tert-butyl)phenyl)urea
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| Synonyms |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3 mg/mL (5.56 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 3 mg/mL (5.56 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 3 mg/mL (5.56 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8530 mL | 9.2649 mL | 18.5298 mL | |
| 5 mM | 0.3706 mL | 1.8530 mL | 3.7060 mL | |
| 10 mM | 0.1853 mL | 0.9265 mL | 1.8530 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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