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GSK2656157
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
GSK2656157图片
CAS NO:1337532-29-2
规格:≥98%
包装与价格:
包装价格(元)
2mg电议
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)416.45
FormulaC23H21FN6O
CAS No.1337532-29-2
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 32 mg/mL (76.83 mM)
Water: <1 mg/mL (slightly soluble or insoluble)
Ethanol: <1 mg/mL
SynonymGSK2656157; GSK 2656157; GSK-2656157
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
实验参考方法
In Vitro

Kinase Assay: Inhibitory potency of GSK2656157 is measured using recombinant GST-PERK (536–1116 amino acids) with 6-His-full-length human eIF2a as a substrate. Kinase selectivity is evaluated using 27 kinases at GSK as well as a panel of 300 kinases.


Cell Assay: human tumor cell lines, primary human microvascular endothelial cells; ~3 μM; 3 days; Antiproliferative activity of GSK2656157 against multiple human tumor cell lines as well as primary human microvascular endothelial cells is evaluated in a 3-day proliferation assay using standard culture medium. In the absence of exogeneous UPR inducers, GSK2656157 has no significant effect on the growth of any of these cells with IC50 range of 6–25 mM.

Pretreatment of cells with GSK2656157 results in inhibition of PERK activation as well as decreases in the downstream substrates, phospho-eIF2a, ATF4, and CHOP with an IC50 in the range of 10-30 nM. Cells that are exposed to 1 mM GSK2656157 before UPR induction are able to block this effect on de novo protein synthesis. Five of 84 UPR-related genes (DDIT3, HERPUD1, PPP1R15A, C/EBP-beta, and ERN1) are down regulated more than 4-fold by GSK2656157. In the absence of exogeneous UPR inducers, GSK2656157 has no significant effect on the growth of any of these cells with IC50 range of 6–25 mM. Thus, GSK2656157 can be used to evaluate the biologic function of PERK in various biologic contexts.

In VivoComplete inhibition of phospho-PERK Thr980 is observed through 8 hours after a single 50 mg/kg oral dose of GSK2656157. Treatment of mice with 50 or 150 mg/kg twice daily dosing of GSK2656157 results in dose-dependent inhibition of tumor growth in four models; reaching 54–114% tumor growth inhibition at the 150 mg/kg, twice daily dose. Altered amino acid metabolism, decreased blood vessel density, and vascular perfusion are potential mechanisms for the observed antitumor effect. Treatment of mice with GSK2656157 results in inhibition of tumor growth in multiple human tumor xenografts.
Animal modelhuman tumor xenograft models
Formulation & Dosage 00.5% hydroxypropyl methyl cellulose, 0.1% tween-80 in water (pH 6.75); 150 mg/kg; BID; Oral
References[1] Atkins C, et al. Cancer Res, 2013, 73(6), 1993-2002.