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GSK2126458

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Catalog No.
A8556
PI3K/mTOR抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,300.00
现货
5mg
¥ 1,200.00
现货
10mg
¥ 1,500.00
现货
50mg
¥ 4,200.00
现货

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Background

GSK2126458 is an inhibitor of PI3K/mTOR with Ki value of 19 pM for PI3K [1].
PI3K (phosphoinositide 3-kinase) plays an important role in regulating cell growth and transformation, and mTOR (mammalian target of rapamycin) which works as a class IV PI3K protein kinase, is also a crucial regulator of cell growth [2]. It has been shown that up-regulation of PI3K/mTOR (phosphatidylinositol-3' kinase/mammalian target of rapamycin) signaling is widespread in carcinoma which may be worked as a biomarker used in clinic [3].
GSK2126458 is a highly potent inhibitor of PI3K/mTOR. When subjected to colorectal cancer cell lines, GSK2126458 could potentiate the cells antiproliferative activity via combining with DDR1-IN-1[4]. In BT474 breast cancer lines, treated with GSK2126458 could be the arrest of G1 cell cycle and thus inhibit cell proliferation [5]. GSK2126458 also could improve the sensitivity of NPC cells to radiation and suppress tumor progression [1].  
In a 5-8F xenograft model with NPC, treated the mouse with GSK2126458 combining of IR significantly inhibited the tumor growth [1]. In mice injected with cancer cells from melanoma patient resisted to the combination of divergent and trametinib, GSK2126458 combined with dabrafenib, trametinib treatment resulted in sustained inhibition of tumor growth[3].
GSK2126458 may play a significant role in regulating autophagy [6].
References:
1.Liu, T., et al., Dual PI3K/mTOR inhibitors, GSK2126458 and PKI-587, suppress tumor progression and increase radiosensitivity in nasopharyngeal carcinoma. Mol Cancer Ther, 2014. 12.
2.Simpson, D.R., L.K. Mell, and E.E. Cohen, Targeting the PI3K/AKT/mTOR pathway in squamous cell carcinoma of the head and neck: Oral Oncol. 2014 Dec 17. pii: S1368-8375(14)00351-0. doi: 10.1016/j.oraloncology.2014.11.012.
3.Villanueva, J., et al., Concurrent MEK2 mutation and BRAF amplification confer resistance to BRAF and MEK inhibitors in melanoma. Cell Rep, 2013. 4(6): p. 1090-9.
4.Kim, H.G., et al., Discovery of a potent and selective DDR1 receptor tyrosine kinase inhibitor. ACS Chem Biol, 2013. 8(10): p. 2145-50.
5.Knight, S.D., et al., Discovery of GSK2126458, a Highly Potent Inhibitor of PI3K and the Mammalian Target of Rapamycin. ACS Med Chem Lett, 2010. 1(1): p. 39-43.
6.Zhang, Y., et al., Screening of kinase inhibitors targeting BRAF for regulating autophagy based on kinase pathways. Mol Med Rep, 2014. 9(1): p. 83-90.

文献引用

1. Smich, Joanna. "Radiation response and PI3K/mTOR targeting in canine melanoma." The University of Guelph.2016.09.06

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt505.5
Cas No.1086062-66-9
FormulaC25H17F2N5O3S
SynonymsGSK212; GSK-2126458; GSK 2126458; GSK-212; GSK 212
Solubility≥25.3mg/mL in DMSO
Chemical Name2,4-difluoro-N-[2-methoxy-5-(4-pyridazin-4-ylquinolin-6-yl)pyridin-3-yl]benzenesulfonamide
SDFDownload SDF
Canonical SMILESCOC1=C(C=C(C=N1)C2=CC3=C(C=CN=C3C=C2)C4=CN=NC=C4)NS(=O)(=O)C5=C(C=C(C=C5)F)F
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

NPC细胞系 (CNE-2、5-8F和6-10B)

溶解方法

该化合物在DMSO中的溶解度大于25.3 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

0.003 mmol/L

应用

低纳摩尔浓度的GSK2126458以浓度和时间依赖的方式降低NPC细胞的活力。GSK2126458抑制NPC细胞的迁移和侵袭。用GSK2126458治疗导致G1期细胞百分比增加。

动物实验 [1]:

动物模型

携带5-8F细胞的雌性BALB/c-nu/nu裸鼠

给药剂量

300 μg/kg,胃内给药每天一次,每周连续5天。

应用

IR与GSK2126458的组合导致异种移植物体积减少超过50%和肿瘤再生延迟。单独使用GSK2126458或PKI-587治疗可以轻度抑制肿瘤生长。

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]. Liu T, Sun Q, Li Q, et al. Dual PI3K/mTOR inhibitors, GSK2126458 and PKI-587, suppress tumor progression and increase radiosensitivity in nasopharyngeal carcinoma[J]. Molecular cancer therapeutics, 2015, 14(2): 429-439.

生物活性

描述 GSK2126458是一种高选择性的和有效的p110α/β/δ/γ和mTORC1/2抑制剂,Ki值分别为0.019 nM/0.13 nM/0.024 nM/0.06 nM和0.18 nM/0.3 nM。
靶点 p110α p110δ p110γ p110β mTORC1 mTORC2
IC50 0.019 nM(Ki) 0.024 nM(Ki) 0.06 nM(Ki) 0.13 nM(Ki) 0.18 nM(Ki) 0.3 nM(Ki)

质量控制

化学结构

GSK2126458

相关生物数据

CORM-3