GSK126
(Synonyms: EZH2 inhibitor;GSK-126;GSK 126) 目录号 : GC15783
A selective EZH2 inhibitor
Cas No.:1346574-57-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Kinase experiment [1]: | |
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Inhibitory activities |
Biochemical assays used the five-member PRC2 complex (human Flag-EZH2, EED, SUZ12, AEBP2, RbAp48) containing either wild-type or mutant EZH2, [3H]-SAM and histone H3 peptides (21-44) with K27me0, K27me1 or K27me2 were used as substrates, reactions were incubated for 30 min. Global histone modification levels were determined by enzyme-linked immunosorbent assay (ELISA) or western blot methods using antibodies specific for total histoneH3, H3K27me1, H3K27me2 orH3K27me3. |
| Cell experiment [2]: | |
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Cell lines |
Lu130, H209, and DMS53 small cell lung cancer (SCLC) cell lines. |
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Preparation method |
Dissolved in DMSO. 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 |
0.5, 2, and 8 μM; 72, 144, 192 h. |
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Applications |
GSK126 inhibited cell growth in all the three cell lines at 8 μM. |
| Animal experiment [1]: | |
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Animal models |
Mice using subcutaneous xenografts of KARPAS-422 and Pfeiffer cells. |
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Dosage form |
15, 50, 150 mg/kg, 10 days of once daily; 300 mg/kg twice per week; administered intraperitoneally. |
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Applications |
GSK126 decreases H3K27me3 and increases gene expression in a dose-dependent way. GSK126 completely inhibited tumour growth at 50 mg/kg and increases survival of mice bearing the more aggressive KARPAS-422 tumours. GSK126 was well tolerated at the doses and schedules examined as measured by little to no decrease in body weight. |
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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]. McCabe MT, Ott HM, Ganji G, et al. EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature, 2012, 492(7427): 108-112. [2]. Sato T, Kaneda A, Tsuji S, et al. PRC2 overexpression and PRC2-target gene repression relating to poorer prognosis in small cell lung cancer. Sci Rep, 2013, 3: 1911. |
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GSK126 is an inhibitor of EZH2 with Ki Value of 93 pM [1].
Over-expression of EZH2 has been reported to be correlated with cancer progression and poor prognosis, high grade and high stage in several tumor types. GSK126 is a potent inhibitor of EZH2 and its functional residence time on activated form of EZH2/PRC2 is mush longer than unactivated forms [1]. When tested with lymphoma cell lines, results showed that harboring EZH2 mutations such as Y641N, Y641F or A677G were more sensitivity [2]. In DMS53, Lu30, H209 SCLC cells, cellular growth was inhibited with 0.5, 2, and 8μM GSK126 treatment [3]. And GSK126 could also significantly restore ARNTL expression in ovarian cancer cells thus inhibit cell growth and enhance chemosensitivity of cisplatin [4].
Intermittent dosing of GSK126 treated subcutaneous KARPAS-422 xenografts model could effectively inhibit its growth with or without a 1 week drug holiday. In mouse model with EZH2 mutant DLBCL xenografts, treatment with GSK126 could markedly inhibit its growth [2].
GSK126是EZH2的抑制剂，Ki值为93 pM [1]。
EZH2的过度表达已被报道与多种肿瘤类型的癌症进展和预后差、高级别和高分期相关。GSK126是EZH2的有效抑制剂，其在激活的EZH2/PRC2上的功能寿命比未激活的形式长得多 [1]。当使用淋巴瘤细胞系进行测试时，结果显示，携带EZH2突变如Y641N、Y641F或A677G的细胞更为敏感 [2]。在DMS53、Lu30、H209 SCLC细胞中，0.5、2和8μM的GSK126治疗可抑制细胞生长[3]。GSK126还可以显著恢复卵巢癌细胞中的ARNTL表达，从而抑制细胞生长并增强顺铂的化疗敏感性 [4]。
间歇给药的GSK126治疗皮下KARPAS-422异种移植瘤模型能够有效抑制其生长，无论是否有一周的药物停用期。在EZH2突变的DLBCL异种移植瘤小鼠模型中，GSK126治疗可显著抑制其生长[2]。
References:
1. Sato, T., et al., PRC2 overexpression and PRC2-target gene repression relating to poorer prognosis in small cell lung cancer. Sci Rep, 2013. 3(1911).
2. McCabe, M.T., et al., EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature, 2012. 492(7427): p. 108-12.
3. Van Aller, G.S., et al., Long residence time inhibition of EZH2 in activated polycomb repressive complex 2. ACS Chem Biol, 2014. 9(3): p. 622-9.
4. Yeh, C.M., et al., Epigenetic silencing of ARNTL, a circadian gene and potential tumor suppressor in ovarian cancer. Int J Oncol, 2014. 45(5): p. 2101-7.
| Cas No. | 1346574-57-9 | SDF | |
| 别名 | EZH2 inhibitor;GSK-126;GSK 126 | ||
| 化学名 | 1-[(2S)-butan-2-yl]-N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-3-methyl-6-(6-piperazin-1-ylpyridin-3-yl)indole-4-carboxamide | ||
| Canonical SMILES | CCC(C)N1C=C(C2=C(C=C(C=C21)C3=CN=C(C=C3)N4CCNCC4)C(=O)NCC5=C(C=C(NC5=O)C)C)C | ||
| 分子式 | C31H38N6O2 | 分子量 | 526.67 |
| 溶解度 | ≥ 3.29 mg/mL in DMSO, <2.4 mg/mL in EtOH, <2.27 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 | 1.8987 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。