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GSK2656157

现货
Catalog No.
B2175
PERK抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 990.00
现货
5mg
¥ 900.00
现货
10mg
¥ 1,200.00
现货
50mg
¥ 2,550.00
现货
100mg
¥ 4,650.00
现货

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Background

GSK2656157 is a highly selective inhibitor of protein kinase R-like ER kinase (PERK) with IC50 value of 0.9nM [1].

GSK2656157 is highly selective for PERK enzyme against a panel of 300 kinases. In the BxPC3 pancreatic tumor cell line, treatment of GSK2656157 causes an inhibition of PERK and decreases in the downstream substrates, including phospho-eIF2α, ATF4 and CHOP. The inhibition of PERK results in effects on de novo protein synthesis as shown in BxPC3 cells [1].

In vivo assay shows that a single 50 mg/kg oral dose of GSK2656157 can completely inhibit the Thr980 phosphorylation of endogenous pancreatic PERK in mice. Furthermore, GSK2656157 causes dose-dependent inhibition of tumor growth in human tumor xenograft models of pancreatic cancer (BxPC3, HPAC and Capan2) and multiple myeloma (NCI-H929). Among these cancers, the Capan2 tumor is most sensitive [1].

References:
[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.

文献引用

1. 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
2. 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

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt416.45
Cas No.1337532-29-2
FormulaC23H21FN6O
Solubility≥20.8225mg/mL in DMSO
Chemical Name1-(5-(4-amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-4-fluoroindolin-1-yl)-2-(6-methylpyridin-2-yl)ethanone
SDFDownload SDF
Canonical SMILESNC1=NC=NC2=C1C(C3=CC=C4C(CCN4C(CC5=NC(C)=CC=C5)=O)=C3F)=CN2C
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

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。GSK2656157处理的细胞通过增加eIF2α磷酸化来补偿PERK的损失。

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.

生物活性

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

化学结构

GSK2656157

相关生物数据

GSK2656157