| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
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EPZ004777 hydrochloride, the hydrochloride salt of EPZ-004777, is a novel and potent DOT1L inhibitor with an IC50 value of 400 pM. DOT1L is a protein methyltransferase catalyzing the methylation of lysine 4 of histone H3 (H3K4).
| ln Vitro |
EPZ004777 hydrochloride, with an IC50 of 400±100 pM, has a strong concentration-suspension inhibitory action on DOT1L enzyme activity. On DOT1L, solutions of hydrochloride EPZ004777 suspend more HMTs (PRMT5, 521±137 nM; other, >50 μM). Prolonged HCl treatment with EPZ004777 has a substantial potential impact on MLL-rearranged cell lines. EPZ004777 hydrochloride markedly decreased the amount of viable MV4-11 and MOLM-13 cells, however it took some time for Jurkat cells to start growing. While Part One MV4-11 cells continued to divide when exposed to EPZ004777 hydrochloride, their population size did not alter over time, according to long-term growth curve tracking. At doses of 3 μM or above, EPZ004777 hydrochloride significantly inhibits MLL-AF9. Results MLL-AF10 and CALM-AF10 transformed cells' bone marrow stroma are inhibited by the EPZ004777 hydrochloride cycle [2].
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| ln Vivo |
The hydrochloride of EPZ004777 was well tolerated, and no appreciable toxicity was seen. Following 14 days of nonstop exposure to EPZ004777 hydrochloride, a complete blood count study revealed a substantial rise in total leukocytes as a result of an increase in neutrophils, monocytes, and lymphocytes. The hydrochloride dosage of EPZ004777 (50, 100, or 150 mg/mL) was well tolerated, and no appreciable weight loss was seen [1].
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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. [3]. Deshpande AJ, et al. Leukemic transformation by the MLL-AF6 fusion oncogene requires the H3K79 methyltransferase Dot1l.Blood. 2013 Mar 28;121(13):2533-41 |
| Molecular Formula |
C₂₈H₄₂CLN₇O₄
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|---|---|
| Molecular Weight |
576.13
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| CAS # |
1380316-03-9
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| Related CAS # |
EPZ004777;1338466-77-5
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| SMILES |
NC1=C2C(N([C@H]3[C@H](O)[C@H](O)[C@@H](CN(C(C)C)CCCNC(NC4=CC=C(C(C)(C)C)C=C4)=O)O3)C=C2)=NC=N1.[H]Cl
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| Synonyms |
EPZ 004777 HCl EPZ-004777 EPZ004777
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| 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) |
H2O : ~100 mg/mL (~173.57 mM)
DMSO : ~100 mg/mL (~173.57 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (173.57 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7357 mL | 8.6786 mL | 17.3572 mL | |
| 5 mM | 0.3471 mL | 1.7357 mL | 3.4714 mL | |
| 10 mM | 0.1736 mL | 0.8679 mL | 1.7357 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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