EPZ004777 |
| رقم الكتالوجGC13383 |
EPZ004777, as a potent epigenetic modulators, can reverse TGF-β1 induced T regulatory cells and may be used to treat diverse immune disorders.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1338466-77-5
Sample solution is provided at 25 µL, 10mM.
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EPZ004777, as a potent epigenetic modulators, can reverse TGF-β1 induced T regulatory cells and may be used to treat diverse immune disorders[1].
In vitro, EPZ004777 has concentration-dependent inhibition of DOT1L enzyme activity with an IC50 of 400 ± 100 pM. In vitro experiment it shown that in MV4-11 cells incubated with 3 μM EPZ004777, a concentration sufficient for maximal cellular DOT1L inhibition. After treatment with 1 day, there is a apparently modest reduction in H3K79me2 levels, but full depletion took 4–5 days. In vitro efficacy test it exhibited that treatment with 3 μM EPZ004777 caused a concentration-dependent decrease of both transcripts in each cell line with IC50 s of approximately 700 nM.[2] In vitro, treatment with 30 μM and 50 μM EPZ004777 obviously decreased cell viability of SW480 cells in a dose-dependent manner. Also 30 μM, 50 μM, and 70 μM EPZ004777 treatment in a dose-dependent manner inhibited the cell viability of HCT116 cells.[3] In vitro, EPZ004777 could also inhibit the proliferation and induce the differentiation of YBT-5 cells[4].
In vivo, nude mice bearing MV4-11 xenograft tumors loaded with a 50 mg/ml solution of EPZ004777, H3K79me2 levels were markedly decreased in tumors from mice treated with EPZ004777 compared to untreated controls.[2] In vivo experiment it demonstated that treatment with 10 and 50?mg/kg EPZ004777 via subconjunctival injection could alleviate corneal injury and opacity.[5].
References:
[1]Premkumar K, Shankar BS. Identification of EPZ004777 and FG2216 as inhibitors of TGF-β1 induced Treg cells by screening a library of epigenetic compounds. Life Sci. 2022 Jul 15;301:120643.
[2]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.
[3]Yang L, et al. Silencing or inhibition of H3K79 methyltransferase DOT1L induces cell cycle arrest by epigenetically modulating c-Myc expression in colorectal cancer. Clin Epigenetics. 2019 Dec 30;11(1):199.
[4]Wang Z, et al. Establishment and characterization of a DOT1L inhibitor-sensitive human acute monocytic leukemia cell line YBT-5 with a novel KMT2A-MLLT3 fusion. Hematol Oncol. 2019 Dec;37(5):617-625.
[5]Wan S, et al. Dot1l Aggravates Keratitis Induced by Herpes Simplex Virus Type 1 in Mice via p38 MAPK-Mediated Oxidative Stress. Oxid Med Cell Longev. 2021 Feb 15;2021:6612689.
| Cell experiment [1]: | |
|
Cell lines |
RAW264.7 cells |
|
Preparation Method |
DOT1L enzyme inhibition enhances OC fusion and resorption ability a RAW264.7 cells pretreated with DMSO or the indicated concentrations of DOT1L inhibitors (EPZ5676 and EPZ004777) and stimulated with RANKL for 60 h. OCs were fixed and stained for TRAP. |
|
Reaction Conditions |
1 and 10 µM; 5 days |
|
Applications |
Treatment with DOT1L inhibitors (EPZ5676 and EPZ004777) increased the proportion and number of large OCs, which was approximately twice that observed in the control group. Furthermore, no significant difference was observed between the effects of treatment at 1 and 10 µM of the DOT1L inhibitors. |
| Animal experiment [2]: | |
|
Animal models |
BALB/c-nu mice |
|
Preparation Method |
1 × 106 HCT116 cells were subcutaneously injected in the left flank of the BALB/c-nu mice. After tumor pumped, the mice were randomly divided into two groups. One group was treated with PBS with 10% DMSO, while the other group was treated with EPZ004777 (100 mg/kg/day, diluted into PBS with 10% DMSO) for 16 days. At the termination of the experiment, tumors were removed and weighed. |
|
Dosage form |
100 mg/kg/day; i.p. |
|
Applications |
The results showed that the tumor volumes and weights of all EPZ004777-treated tumors in the nude mice were significantly smaller and lighter than the control groups, respectively. |
|
References: [1]. Gao Y, Ge W. The histone methyltransferase DOT1L inhibits osteoclastogenesis and protects against osteoporosis. Cell Death Dis. 2018 Jan 18;9(2):33. [2]. Yang L, et al. Silencing or inhibition of H3K79 methyltransferase DOT1L induces cell cycle arrest by epigenetically modulating c-Myc expression in colorectal cancer. Clin Epigenetics. 2019 Dec 30;11(1):199. |
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| Cas No. | 1338466-77-5 | SDF | |
| Chemical Name | 1-[3-[[(2R,3S,4R,5R)-5-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxyoxolan-2-yl]methyl-propan-2-ylamino]propyl]-3-(4-tert-butylphenyl)urea | ||
| Canonical SMILES | CC(C)N(CCCNC(=O)NC1=CC=C(C=C1)C(C)(C)C)CC2C(C(C(O2)N3C=CC4=C3N=CN=C4N)O)O | ||
| Formula | C28H41N7O4 | M.Wt | 539.67 |
| الذوبان | ≥ 27 mg/mL in DMSO, ≥ 94.6 mg/mL in EtOH with ultrasonic | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.853 mL | 9.2649 mL | 18.5298 mL |
| 5 mM | 0.3706 mL | 1.853 mL | 3.706 mL |
| 10 mM | 0.1853 mL | 0.9265 mL | 1.853 mL |
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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