GSK2656157

Catalog No.S7033

For research use only.

GSK2656157 is an ATP-competitive and highly selective inhibitor of PERK with IC50 of 0.9 nM in a cell-free assay, 500-fold greater against a panel of 300 kinases. GSK2656157 decreases apoptosis and inhibits excessive autophagy.

GSK2656157 Chemical Structure

CAS No. 1337532-29-2

Selleck's GSK2656157 has been cited by 32 publications

Purity & Quality Control

Choose Selective PERK Inhibitors

Biological Activity

Description GSK2656157 is an ATP-competitive and highly selective inhibitor of PERK with IC50 of 0.9 nM in a cell-free assay, 500-fold greater against a panel of 300 kinases. GSK2656157 decreases apoptosis and inhibits excessive autophagy.
Features Orally bioavailable PERK-selective inhibitor that functions independent of eIF2α phosphorylation.
Targets
PERK [1]
(Cell-free assay)
0.9 nM
In vitro

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. [1]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human A549 cells M2DSXmZ2dmO2aX;uJIF{e2G7 MnnZNUBp NEOxUWhKdmirYnn0bY9vKG:oIIToZZB{cWejcnfpck1qdmS3Y3XkJIF2fG:yaH;zdIhwenmuYYTpc44hd2ZiUFXST{BqdiCqdX3hckBCPTR7IHPlcIx{KHC{ZXnuZ5Vj[XSnZDDmc5IhOSCqcjDmc4xtd3enZDDifUB1cGGyc3nnZZJocW5vaX7keYN1cW:wIH3lZZN2emWmIHHmeIVzKDFiaIKgZpkhX2W|dHXyckBjdG:2dHnu[{BidmGueYPpd{whUUN3ME2wMlA{KM7:TR?= NXPJR4ljRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFA2QTNpPkK0PVAxPTl|PD;hQi=>
In vivo Complete 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. [1]

Protocol (from reference)

Kinase Assay:

[1]

  • 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 Research:

[1]

  • Cell lines: human tumor cell lines, primary human microvascular endothelial cells
  • Concentrations: ~3 μM
  • Incubation Time: 3 day
  • Method:

    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.

Animal Research:

[1]

  • Animal Models: human tumor xenograft models
  • Dosages: 50 or 150 mg/kg, twice daily
  • Administration: Orally

Solubility (25°C)

In vitro

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
1% CMC Na
For best results, use promptly after mixing.

30mg/mL

Chemical Information

Molecular Weight 416.45
Formula

C23H21FN6O

CAS No. 1337532-29-2
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC1=NC(=CC=C1)CC(=O)N2CCC3=C2C=CC(=C3F)C4=CN(C5=NC=NC(=C45)N)C

In vivo Formulation Calculator (Clear solution)

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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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