EPZ015666
(Synonyms: GSK3235025) 目录号 : GC15302
A bioavailable PRMT5 inhibitor
Cas No.:1616391-65-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| 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. |
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Reacting condition |
0.0007 ~ 5 μM |
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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]: | |
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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 |
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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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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.
| Cas No. | 1616391-65-1 | SDF | |
| 别名 | GSK3235025 | ||
| 化学名 | (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 | ||
| 分子式 | C20H25N5O3 | 分子量 | 383.44 |
| 溶解度 | ≥ 19.17mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。