GSK503
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
GSK503是EZH2的强效抑制剂.
zeste基因增强子同源物2(EZH2)是一种组蛋白赖氨酸N-甲基转移酶,催化组蛋白3赖氨酸27的三甲基化(H3K27me3),随后诱导染色质浓缩,从而抑制靶基因转录.
GSK503是一种有效的EZH2抑制剂,具有抗癌活性.在人黑色素瘤细胞中,GSK503显著减少H3K27me3水平,诱导G1期细胞周期阻滞,减慢细胞生长[1].
在小鼠中,GSK503诱导大约10%的可逆的体重减轻.在皮肤黑色素瘤小鼠中,GSK503减少肿瘤和间质细胞的H3K27me3水平,并显著减少新的皮肤黑色素瘤出现.此外,GSK503显著抑制肿瘤细胞的增殖.在小鼠B16-F10黑素瘤细胞异种移植C57Bl/6小鼠中,GSK503显著降低H3K27me3水平,抑制肿瘤生长.此外,GSK503抑制黑色素瘤的淋巴结和肺转移,减少肺结节数量.GSK503增加脱氧胞苷激酶(DCK)\腺苷甲硫氨酸脱羧酶1(AMD1)和WD重复结构域19(WDR19) 的表达,这些均是EZH2的靶基因[1].
参考文献:
[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.
- 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
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 526.67 |
Cas No. | 1346572-63-1 |
Formula | C31H38N6O2 |
Solubility | ≥21.65 mg/mL in DMSO; insoluble 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 |
SDF | Download SDF |
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 |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 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。溶液形式一般不宜长期储存,请尽快用完。 |
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. |
质量控制和MSDS
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