GSK2656157
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.
GSK2656157是一种蛋白激酶R样ER激酶(PERK)的高选择性抑制剂,IC50值为0.9 nM[1].
与300种激酶相比,GSK2656157对PERK具有高选择性.在BxPC3胰腺癌细胞系中,GSK2656157可抑制PERK,减少下游底物,包括磷酸化-eIF2α\ATF4和CHOP.在BxPC3细胞中,对PERK的抑制可导致对蛋白从头合成的影响[1].
体内试验表明单次口服50 mg/kg的GSK2656157可完全抑制小鼠内源胰腺PERK的Thr980磷酸化.此外,在人类胰腺癌(BxPC3\HPAC和Capan2)肿瘤和多发性骨髓瘤(NCI-H929)异种移植模型中,GSK2656157可剂量依赖地抑制肿瘤生长.在这些癌症中,Capan2肿瘤最为敏感[1].
参考文献:
[1] Atkins C, Liu Q, Minthorn E, Zhang SY, Figueroa DJ, Moss K, Stanley TB, Sanders B, Goetz A, Gaul N, Choudhry AE, Alsaid H, Jucker BM, Axten JM, Kumar R. Characterization of a novel PERK kinase inhibitor with antitumor and antiangiogenic activity. Cancer Res. 2013 Mar 15;73(6):1993-2002.
- 1. Ploingarm Petsophonsakul, Mathias Burgmaier, et al. "Nicotine promotes vascular calcification via intracellular Ca2+-mediated, Nox5-induced oxidative stress, and extracellular vesicle release in vascular smooth muscle cells." Cardiovasc Res. 2022 Jul 20;118(9):2196-2210. PMID: 34273166
- 2. Luo J, Xia Y, et al. "GRP78 inhibition enhances ATF4-induced cell death by the deubiquitination and stabilization of CHOP in human osteosarcoma." Cancer Lett. 2017 Sep 22. pii:S0304-3835(17)30571-2. PMID: 28947141
- 3. Rojas-Rivera D, Delvaeye T, et al. "When PERK inhibitors turn out to be new potent RIPK1 inhibitors:critical issues on the specificity and use of GSK2606414 and GSK2656157." Cell Death Differ. 2017 Jun;24(6):1100-1110. PMID: 28452996
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 416.45 |
Cas No. | 1337532-29-2 |
Formula | C23H21FN6O |
Solubility | insoluble in H2O; ≥2.5 mg/mL in EtOH with gentle warming and ultrasonic; ≥20.82 mg/mL in DMSO |
Chemical Name | 1-(5-(4-amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-4-fluoroindolin-1-yl)-2-(6-methylpyridin-2-yl)ethanone |
SDF | Download SDF |
Canonical SMILES | NC1=NC=NC2=C1C(C3=CC=C4C(CCN4C(CC5=NC(C)=CC=C5)=O)=C3F)=CN2C |
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 |
HT1080细胞 |
溶解方法 |
在DMSO中的溶解度大于20.8 mg/mL。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。 |
反应条件 |
0.1-10 μM,24 h |
应用 |
在HT1080细胞中,0.1 μM的GSK2656157能够有效的抑制PERK的活性。 |
动物实验[2]: | |
动物模型 |
8-12周龄的雌性空白CD-1小鼠,雌性CD-1裸鼠和严重联合免疫缺陷(SUID)小鼠 |
剂量 |
50,150 mg/kg,每天两次 |
应用 |
50 mg/kg单剂量口服给药后8小时内,小鼠胰腺中PERK的磷酸化几乎被完全抑制,18小时时PERK活性几乎恢复到正常水平。每天两次50或150 mg/kg GSK2656157给药以剂量依赖的方式抑制小鼠多种异种移植瘤的生长。 |
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]. Krishnamoorthy J, Rajesh K, Mirzajani F, et al. Evidence for eIF2α phosphorylation-independent effects of GSK2656157, a novel catalytic inhibitor of PERK with clinical implications[J]. Cell Cycle, 2014, 13(5): 801-806. [2]. Atkins C, Liu Q, Minthorn E, et al. Characterization of a novel PERK kinase inhibitor with antitumor and antiangiogenic activity[J]. Cancer research, 2013, 73(6): 1993-2002. |
Description | GSK2656157是一种ATP竞争性的PERK高选择性抑制剂,IC50值为0.9 nM. | |||||
靶点 | PERK | |||||
IC50 | 0.9 nM |
质量控制和MSDS
- 批次: