EPZ015666 (Synonyms: GSK3235025) |
| Catalog No.GC15302 |
EPZ015666 (GSK3235025) es un inhibidor de PRMT5 disponible por vÍa oral con una IC50 de 22 nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1616391-65-1
Sample solution is provided at 25 µL, 10mM.
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EPZ015666 is a potent and selective inhibitor of PRMT5 with IC50 value of 22 nM [1].
Protein arginine methyltransferase-5 (PRMT5) is an enzyme that plays an important role in many cellular processes including tumorigenesis [1].
EPZ015666 is an orally bioavailable PRMT5 inhibitor. In a competitive inhibition model, EPZ015666 inhibited PRMT5 with Ki value of 5 nM and exhibited >20000-fold selectivity over 20 other protein methyltransferases (PMTs). In MCL cell lines Z-138, Mino, Maver-1, Granta-519 and Jeko-1, EPZ015666 decreased the level of SmD3, which was a PRMT5 substrate in a concentration-dependent way. Also, EPZ015666 reduced SmD3me2s in all cell lines. The cellular thermal shift assay (CETSA) in A375 cells showed that EPZ015666 specifically bound to PRMT5. EPZ015666 showed potent antiproliferative effects with IC50 values of 96, 450 and 61-904 nM for Z-138, Maver-1 and additional MCL cell lines respectively in a concentration-dependent way [1].
In SCID mice bearing Z-138 and Maver-1 xenografts, EPZ015666 (25, 50, 100 and 200 mg/kg) showed tumor-growth inhibition (TGI) in a dose-dependent way [1].
Reference:
[1]. Chan-Penebre E, Kuplast KG, Majer CR, et al. A selective inhibitor of PRMT5 with in vivo and in vitro potency in MCL models. Nat Chem Biol, 2015, 11(6): 432-437.
| Cell experiment [1]: | |
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Cell lines |
Z-138 and Maver-1 cells |
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Preparation method |
The solubility of this compound in DMSO is > 19.2 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
|
Reacting condition |
0.0007 ~ 5 μM |
|
Applications |
In Z-138 and Maver-1 cells, EPZ015666 potently inhibited cell proliferation in a concentration-dependent manner, with the IC50 values of 96 nM and 450 nM, respectively. |
| Animal experiment [1]: | |
|
Animal models |
SCID mice bearing Z-138 and Maver-1 xenografts |
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Dosage form |
25, 50, 100 and 200 mg/kg; p.o.; b.i.d., for 21 days |
|
Applications |
EPZ015666, at all indicated doses, significantly affected weight, volume and tumor growth of SCID mice bearing Z-138 and Maver-1 xenografts. At the dose of 200 mg/kg, EPZ015666 induced tumor stasis in Z-138 cells and Maver-1 cells, with the TGI values of > 93% and > 70%, respectively. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Chan-Penebre E, Kuplast KG, Majer CR, et al. A selective inhibitor of PRMT5 with in vivo and in vitro potency in MCL models. Nat Chem Biol, 2015, 11(6): 432-437. |
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| Cas No. | 1616391-65-1 | SDF | |
| Sinónimos | GSK3235025 | ||
| Chemical Name | (R)-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)-6-(oxetan-3-ylamino)pyrimidine-4-carboxamide | ||
| Canonical SMILES | O=C(C1=CC(NC2COC2)=NC=N1)NC[C@@H](O)CN(CC3)CC4=C3C=CC=C4 | ||
| Formula | C20H25N5O3 | M.Wt | 383.44 |
| Solubility | ≥ 19.17mg/mL in DMSO | 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. |
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| 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 | 2.608 mL | 13.0398 mL | 26.0797 mL |
| 5 mM | 0.5216 mL | 2.608 mL | 5.2159 mL |
| 10 mM | 0.2608 mL | 1.304 mL | 2.608 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
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. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
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.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 38 reference(s) in Google Scholar.)
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