EPZ005687
(Synonyms: EPZ 005687,EPZ-005687) 目录号 : GC13878
A potent, selective inhibitor of EZH2
Cas No.:1396772-26-1
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
| Kinase experiment [1]: | |
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Biochemical enzyme assays |
Compound was incubated for 30 mins with 40 μL per well of 5 nM PRC2 (final assay concentration in 50 μL was 4 nM) in 1× assay buffer (20 mM Bicine [pH 7.6], 0.002% Tween-20, 0.005% Bovine Skin Gelatin and 0.5 mM DTT). 10 μL per well of substrate mix comprising assay buffer 3H-SAM, unlabeled SAM, and peptide representing histone H3 residues 21-44 containing C-terminal biotin (appended to a C-terminal amide-capped lysine) were added to initiate the reaction (both substrates were present in the final reaction mixture at their respective Km values, an assay format referred to as “balanced conditions”). The final concentrations of substrates and methylation state of the substrate peptide were indicated for each enzyme. Reactions were incubated for 90 mins at room temperature and quenched with 10 μL per well of 600 μM unlabeled SAM. The mixtures were then transferred to a 384-well flashplate and washed after 30 mins. |
| Cell experiment [1]: | |
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Cell lines |
OCI-LY19, WSU-DLCL2 and Pfeiffer cells |
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Preparation method |
The solubility of this compound in DMSO is limited. 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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Reaction Conditions |
0.011 ~ 8.3 μM; 11 days |
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Applications |
EPZ005687 significantly inhibited the proliferation of WSU-DLCL2 and Pfeiffer cells, with minimal effects on the proliferation of OCI-LY19 cells. |
| Animal experiment [2]: | |
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Animal models |
Osteoarthritis (OA) mouse model |
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Dosage form |
5.6 μM, 50 μL; intra-articular injection; at 7th, 15th and 30th days |
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Applications |
Intra-articular injection of EPZ005687 delayed OA development in mice. |
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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, Wigle TJ, Warholic NM, Sneeringer CJ, Allain CJ, Klaus CR, Sacks JD, Raimondi A, Majer CR, Song J, Scott MP, Jin L, Smith JJ, Olhava EJ, Chesworth R, Moyer MP, Richon VM, Copeland RA, Keilhack H, Pollock RM, Kuntz KW. A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells. Nat Chem Biol. 2012 Nov;8(11):890-6. [2]. Chen L, Wu Y, Wu Y, Wang Y, Sun L, Li F. The inhibition of EZH2 ameliorates osteoarthritis development through the Wnt/β-catenin pathway. Sci Rep. 2016 Aug 19;6:29176. | |
EPZ005687 is a potent inhibitor of EZH2, an enzymatic subunit of polycomb repressive complex 2 (PRC2) catalyzing the methylation of histone H3 lysine 27 (H3K27), that inhibits EZH2 with a value of inhibition constant Ki of 24 nM, which is 500-fold and 50-fold greater in selectivity than 15 other protein methyltransferases and closely related EZH1 respectively. EPZ005687 concentration-dependently inhibits the enzymatic activity of PRC2 with a value of 50% inhibition concentration IC50 of 54 nM through binding to the S-adenosylmethionine (SAM) pocket of the EZH2 SET domain. Study results have shown that EPZ005687 reduces H3K27 methylation in a variety of lymphoma cells and induces apoptotic cell killing in heterozygous Tyr641 or Ala677 mutant cells.
Reference
[1].Knutson SK, Wigle TJ, Warholic NM, Sneeringer CJ, Allain CJ, Klaus CR, Sacks JD, Raimondi A, Majer CR, Song J, Scott MP, Jin L, Smith JJ, Olhava EJ, Chesworth R, Moyer MP, Richon VM, Copeland RA, Keilhack H, Pollock RM, Kuntz KW. A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells. Nat Chem Biol. 2012 Nov;8(11):890-6.
| Cas No. | 1396772-26-1 | SDF | |
| 别名 | EPZ 005687,EPZ-005687 | ||
| 化学名 | 1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-6-[4-(morpholin-4-ylmethyl)phenyl]indazole-4-carboxamide | ||
| Canonical SMILES | CC1=CC(=C(C(=O)N1)CNC(=O)C2=C3C=NN(C3=CC(=C2)C4=CC=C(C=C4)CN5CCOCC5)C6CCCC6)C | ||
| 分子式 | C32H37N5O3 | 分子量 | 539.67 |
| 溶解度 | ≥ 3.86 mg/mL in DMSO, <2.29 mg/mL in EtOH, <2.37 mg/mL in Water | 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 | 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 |
| 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。