EPZ-6438
(Synonyms: E-7438,Tazemetostat) 目录号 : GC14062
EPZ-6438 是一种有效且具有生物利用度的 EZH2 抑制剂，EZH2 是多梳抑制复合物 2 (PRC2) 的催化亚基，可催化组蛋白 H3 (H3K27) 的赖氨酸 27 甲基化，从而抑制含有人 PRC2 的活性抑制常数 Ki 值为 2.5 nM 的野生型 EZH2。
Cas No.:1403254-99-8
Sample solution is provided at 25 µL, 10mM.
EPZ-6438 is a potent and bio-available inhibitor of EZH2, the catalytic subunit of polycomb repressive complex 2 (PRC2) catalyzing the methylation of lysine 27 of histone H3 (H3K27), that inhibits the activity of human PRC2-containing wild-type EZH2 with a value of inhibition constant Ki of 2.5 nM. EPZ-6438 competitively binds to the S-adenosylmethionine (SAM) binding site of EZH2 and also non-competitively binds to the binding sites of peptide or nucleosome substrate. EPZ-6438 selectively inhibits EZH2 with selectivity 35-fold greater than EZH1. Study results have suggested that EPZ-6438 exhibits dramatic and permanent anti-tumor activity in MRT models through synergistic effects of EPZ-6438-mediated EZH2 inhibition on several cancer pathways.
EPZ-6438 是一种有效且具有生物利用度的 EZH2 抑制剂，EZH2 是多梳抑制复合物 2 (PRC2) 的催化亚基，可催化组蛋白 H3 (H3K27) 的赖氨酸 27 甲基化，从而抑制含有人 PRC2 的活性抑制常数 Ki 值为 2.5 nM 的野生型 EZH2。 EPZ-6438 竞争性结合 EZH2 的 S-腺苷甲硫氨酸 (SAM) 结合位点，也非竞争性结合肽或核小体底物的结合位点。 EPZ-6438 选择性抑制 EZH2，选择性比 EZH1 高 35 倍。研究结果表明，EPZ-6438 通过 EPZ-6438 介导的 EZH2 抑制对多种癌症通路的协同作用，在 MRT 模型中表现出显着和永久的抗肿瘤活性。
Reference
[1].Sarah K. Knutson1, Natalie M. Warholic, Tim J. Wigle, Christine R. Klaus, Christina J. Allain, Alejandra Raimondi, Margaret Porter Scott, Richard Chesworth, Mikel P. Moyer, Robert A. Copeland, Victoria M. Richon, Roy M. Pollock, Kevin W. Kuntz, and Heike Keilhack. Durable tumor regression in genetically altered malignant rhabdoid tumors by inhibition of methyltransferase EZH2. PNAS 2013; 110(19): 7922-7927
| Cell experiment [1]: | |
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Cell lines |
SMARCB1-deficient MRT cells |
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Preparation method |
Limited solubility. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reaction Conditions |
4-7 days |
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Applications |
EPZ-6438 induces a reduction of global H3K27Me3 level in a concentration-dependent manner. In addition, EPZ-6438 leads to a substantial antiproliferative effects as IC50 values within nanomolar range. Treatment of EPZ-6438 results in expression of CD133, DOCK4, and PTPRK and up-regulates CDKN1A and CDKN2A and BIN1in a time-dependent manner. |
| Animal experiment [2]: | |
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Animal models |
SCID mice bearing EZH2-mutant lymphoma xenografts. |
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Dosage form |
3 times daily every 8 hours, 2 times a day every 12 hours, or once a day schedules for either 7 or 28 days by oral gavage. |
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Applications |
EPZ-6438 dose-dependently causes a reduction of tumor H3K27Me3 levels (EC50 =23 nmol/L). EPZ-6438 also shows a remarkable antitumor effects in a dose dependent manner with 2 cycles of 7-day on/7-day off and 21-day on/7-day off schedules. All EPZ-6438 dose groups except the lowest one leads to complete tumor regressions. |
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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. Knutson SK, Warholic NM, Wigle TJ et al. Durable tumor regression in genetically altered malignant rhabdoid tumors by inhibition of methyltransferase EZH2. Proc Natl Acad Sci U S A. 2013 May 7;110(19):7922-7. 2. Knutson SK, Kawano S, Minoshima Y et al. Selective inhibition of EZH2 by EPZ-6438 leads to potent antitumor activity in EZH2-mutant non-Hodgkin lymphoma. Mol Cancer Ther. 2014 Apr;13(4):842-54. |
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| Cas No. | 1403254-99-8 | SDF | |
| 别名 | E-7438,Tazemetostat | ||
| 化学名 | N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-3-[ethyl(oxan-4-yl)amino]-2-methyl-5-[4-(morpholin-4-ylmethyl)phenyl]benzamide | ||
| Canonical SMILES | CCN(C1CCOCC1)C2=CC(=CC(=C2C)C(=O)NCC3=C(C=C(NC3=O)C)C)C4=CC=C(C=C4)CN5CCOCC5 | ||
| 分子式 | C34H44N4O4 | 分子量 | 572.74 |
| 溶解度 | ≥ 28.637mg/mL in DMSO | 储存条件 | Desiccate 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 | 1.746 mL | 8.73 mL | 17.4599 mL |
| 5 mM | 0.3492 mL | 1.746 mL | 3.492 mL |
| 10 mM | 0.1746 mL | 0.873 mL | 1.746 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。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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