GSK503
目录号 : GC11414
A potent, selective EZH2 inhibitor
Cas No.:1346572-63-1
Sample solution is provided at 25 µL, 10mM.
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GSK503 is a potent inhibitor of EZH2.
Enhancer of zeste homolog 2 (EZH2) is a histone-lysine N-methyltransferase enzyme that catalyses trimethylation of lysine 27 in histone 3 (H3K27me3), and then induces chromatin compaction and consequently inhibits target genes transcription.
GSK503 is a potent EZH2 inhibitor with anticancer activity. In human melanoma cells, GSK503 significantly reduced H3K27me3 levels, induced G1 cell cycle arrest and slowed down cell growth [1].
In mice, GSK503 induced reversible weight loss by ~10%. In mice with skin melanomas, GSK503 reduced H3K27me3 levels in tumour and stromal cells, and significantly reduced the emergence of new skin melanomas. Also, GSK503 significantly inhibited the proliferation of tumour cells. In C57Bl/6 mice xenografted murine B16-F10 melanoma cells, GSK503 significantly reduced H3K27me3 levels and inhibited tumor growth. Also, GSK503 inhibited lymph node and lung metastases of melanoma and reduced lung nodule counts. GSK503 increased the expression of deoxycytidine kinase (DCK), adenosylmethionine decarboxylase 1 (AMD1) and WD repeat domain 19 (WDR19), which were EZH2 target genes [1].
Reference:
[1]. Zingg D, Debbache J, Schaefer SM, et al. The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumour suppressors. Nat Commun, 2015, 6: 6051.
| Cell experiment [1]: | |
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Cell lines |
Human melanoma cells |
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Preparation method |
The solubility of this compound in DMSO is >21.65mg/mL. 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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Reacting condition |
1 μM; 8 days; 37 ℃ |
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Applications |
GSK503 significantly reduced H3K27me3 levels, induced G1 cell cycle arrest and slowed down cell growth. |
| Animal experiment [1]: | |
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Animal models |
Mice engrafted subcutaneously with melanoma cells, C57Bl/6 mice xenografted murine B16-F10 melanoma cells |
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Dosage form |
Intraperitoneal injections; 150 mg/kg; 35 consecutive days |
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Application |
GSK503 treatment drastically reduced the emergence of new skin melanomas over time after treatment start. GSK503 treatment prevented murine melanoma growth. GSK503 significantly inhibited the proliferation of tumour cells. In C57Bl/6 mice xenografted murine B16-F10 melanoma cells, GSK503 significantly reduced H3K27me3 levels and inhibited tumor growth. GSK503 inhibited lymph node and lung metastases of melanoma and reduced lung nodule counts. |
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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]. Zingg D, Debbache J, Schaefer SM, et al. The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumour suppressors. Nat Commun, 2015, 6: 6051. | |
| Cas No. | 1346572-63-1 | SDF | |
| 化学名 | (Z)-N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)-1-isopropyl-3-methyl-6-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-indole-4-carbimidic acid | ||
| Canonical SMILES | CC(N(C1=CC(C2=CN=C(N3CCN(CC3)C)C=C2)=CC(/C(O)=N/CC4=C(O)N=C(C=C4C)C)=C51)C=C5C)C | ||
| 分子式 | C31H38N6O2 | 分子量 | 526.67 |
| 溶解度 | ≥ 21.65 mg/mL in DMSO, ≥ 26.85 mg/mL in EtOH with gentle warming | 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.8987 mL | 9.4936 mL | 18.9872 mL |
| 5 mM | 0.3797 mL | 1.8987 mL | 3.7974 mL |
| 10 mM | 0.1899 mL | 0.9494 mL | 1.8987 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: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet