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GSK503

现货
Catalog No.
B5833
EZH2抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,500.00
现货
5mg
¥ 900.00
现货
10mg
¥ 1,400.00
现货
50mg
¥ 4,500.00
现货

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Background

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.

文献引用

1. R.Martin Mateos, T.M.De Assuncao, et al. "Enhancer of Zeste Homologue 2 inhibition attenuates TGF-β dependent hepatic stellate cell activation and liver fibrosis." Cellular and Molecular Gastroenterology and Hepatology Available online 15 September 2018.
2. Sarmento OF, Svingen PA, et al. "The Role of the Histone Methyltransferase Enhancer of Zeste Homolog 2 (EZH2) in the Pathobiological Mechanisms Underlying Inflammatory Bowel Disease (IBD)." J Biol Chem. 2017 Jan 13;292(2):706-722. PMID:27909059

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt526.67
Cas No.1346572-63-1
FormulaC31H38N6O2
Solubility≥21.65 mg/mL in DMSO, <2.7 mg/mL in H2O, ≥26.85 mg/mL in EtOH with gentle warming
Chemical Name(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
SDFDownload SDF
Canonical SMILESCC(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
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

人黑色素瘤细胞

溶解方法

该化合物在DMSO中的溶解度大于21.65 mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。

反应条件

1 μM,8天,37 ℃

应用

GSK503显著降低H3K27me3的水平,诱导G1细胞周期停滞并减缓细胞生长。

动物实验 [1]:

动物模型

皮下移植黑色素瘤细胞的小鼠,异种移植鼠B16-F10黑色素瘤细胞的C57B1/6小鼠

给药剂量

腹腔注射,150 mg/kg,持续35天

应用

随着治疗开始后,CGSK503大大减少了新皮肤黑色素瘤的出现。GSK503可预防鼠黑色素瘤的生长。 GSK503显著抑制肿瘤细胞的增殖。在异种移植小鼠B16-F10黑色素瘤细胞的C57Bl/6小鼠中,GSK503显著降低H3K27me3的水平并抑制肿瘤生长。GSK503抑制黑色素瘤的淋巴结转移和肺转移,减少肺结节数。

注意事项

由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。

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.

质量控制

化学结构

GSK503

相关生物数据

GSK503

相关生物数据

GSK503