GSK126
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.
GSK126是EZH2的抑制剂，Ki值为93 pM [1]。
据报道，EZH2的过表达与多种癌症类型中癌症的发展和预后不良相关。GSK126是一种有效的EZH2抑制剂，其对EZH2/PRC2活化形式的作用时间比对非活化形式更长 [1]。在淋巴瘤细胞系中，EZH2突变（比如Y641N、Y641F或A677G）具有更高的敏感性 [2]。在DMS53、LU30和H209小细胞肺癌细胞（SCLC）中，分别用0.5、2和8 μM的GSK126处理细胞后均抑制了细胞生长 [3]。在卵巢癌细胞中，GSK126也可以显著恢复ARNTL的表达，从而抑制细胞生长，提高对cisplatin的敏感性 [4]。
在KARPAS-422皮下异种移植模型中，GSK126间断给药可以有效抑制肿瘤生长。在EZH2突变的DLBCL肿瘤异种移植小鼠模型中，GSK126也可以娴熟抑制肿瘤生长 [2]。
参考文献：
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.
- 1. Baokun Sui, Dong Chen, et al. "A novel antiviral lncRNA, EDAL, shields a T309 O-GlcNAcylation site to promote EZH2 lysosomal degradation." Genome Biol 2020 Sep 1;21(1):228. PMID:32873321
- 2. Meng XL, Fu P, et al. "Increased EZH2 Levels in Anterior Cingulate Cortex Microglia Aggravate Neuropathic Pain by Inhibiting Autophagy Following Brachial Plexus Avulsion in Rats." Neurosci Bull. 2020;10.1007/s12264-020-00502-w. PMID:32346844
- 3. Silasi M, You Y, et al. "Human Chorionic Gonadotropin modulates CXCL10 Expression through Histone Methylation in human decidua." Sci Rep. 2020;10(1):5785. PMID:32238853
- 4. Otsuka Y, Nishikori M, et al. "EZH2 inhibitors restore epigenetically silenced CD58 expression in B-cell lymphomas." Mol Immunol. 2020;119:35–45. PMID:31962268
- 5. Liu Y, Niu Y, et al. "Tat expression led to increased histone 3 tri-methylation at lysine 27 and contributed to HIV latency in astrocytes through regulation of MeCP2 and Ezh2 expression." J Neurovirol. 2019 Apr 24. PMID:31020497
- 6. Hübner JM, Müller T, et al. "EZHIP / CXorf67 mimics K27M mutated oncohistones and functions as an intrinsic inhibitor of PRC2 function in aggressive posterior fossa ependymoma." Neuro Oncol. 2019 Mar 29. pii: noz058. PMID:30923826
- 7. Anastassiia Vertii, Jianhong Ou, et al. "Two Contrasting Classes of Nucleolus-Associated Domains in Mouse Fibroblast Heterochromatin." bioRxiv. 2018 December 03.
- 8. Agnieszka I. Laskowski, Danielle A. Fanslow1,et al. "Clinical Epigenetic Therapies Disrupt Sex Chromosome Dosage Compensation in Human Female Cells." Gender and the Genome 2018, Vol. 2(1) 2-7
- 9. Jalan-Sakrikar N, De Assuncao TM, et al. "Hedgehog Signaling Overcomes an EZH2-Dependent Epigenetic Barrier to Promote Cholangiocyte Expansion." PLoS One. 2016 Dec 9;11(12):e0168266. PMID:27936185
| Storage | Store at -20°C |
| M.Wt | 526.67 |
| Cas No. | 1346574-57-9 |
| Formula | C31H38N6O2 |
| Synonyms | EZH2 inhibitor;GSK-126;GSK 126 |
| Solubility | insoluble in H2O; insoluble in EtOH; ≥4.38 mg/mL in DMSO with gentle warming |
| Chemical Name | 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 |
| SDF | Download SDF |
| 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 |
| 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。 |
| 激酶实验[1]: | |
|
抑制活性 |
使用含有野生型或突变体EZH2的五种PRC2复合体（人Flag-EZH2、EED、SUZ12、AEBP2和RbAp48）以及[3H]-SAM和组蛋白H3肽（21-44）进行生化测定，K27me0、K27me1或K27me2作为反应底物，将反应孵育30分钟。使用针对总组蛋白histoneH3、H3K27me1、H3K27me2或H3K27me3的特异性抗体，通过酶联免疫吸附测定（ELISA）或western印迹方法测定总体组蛋白修饰水平。 |
| 细胞实验[2]: | |
|
细胞系 |
Lu130、H209和 DMS53小细胞癌细胞系（SCLC） |
|
溶解方法 |
溶于DMSO。若配制更高浓度的溶液，一般步骤如下：请将试管置于37°C加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20°C可放置数月 |
|
反应条件 |
0.、2和8 μM；72、144、192 h. |
|
实验结果 |
在所测定的三种细胞系中，8 μM浓度的GSK126抑制细胞生长。 |
| 动物实验[1]: | |
|
动物模型 |
皮下异种移植KARPAS-422和Pfeiffer细胞的小鼠。 |
|
剂量 |
15、50,、150 mg/kg, 每天一次，连续10天；300 mg/kg，每周两次；腹腔内给药 |
|
实验结果 |
GSK126以剂量依赖性的方式降低H3K27me3并增加基因表达。50 mg/kg的GSK126完全抑制肿瘤生长，增加携带侵袭性KARPAS-422肿瘤的小鼠存活。GSK126所测量的剂量耐受性良好，测量过程中没有体重减轻现象。 |
|
注意事项 |
请测试所有化合物在室内的溶解度，实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的，属于正常现象。 |
|
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. |
|
质量控制和MSDS
- 批次:
化学结构
相关生物数据
相关生物数据
相关生物数据
相关生物数据
相关生物数据
相关生物数据
相关生物数据
