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GSK2656157 PERK inhibitor

Name: GSK2656157
Brand: Selleck Chemicals
SKU: S7033
Availability: InStock
Rating: 5 (51 reviews)

Cat.No.S7033

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. This compound decreases apoptosis and inhibits excessive autophagy.

Chemical Structure

Molecular Weight: 416.45

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Quality Control

Batch: Purity: 99.98%

99.98

Related Targets	Bcl-2 Caspase PD-1/PD-L1 Ferroptosis p53 Apoptosis related Synthetic Lethality STAT TNF-alpha Ras
Other PERK Inhibitors	GSK2606414 Salubrinal ISRIB (trans-isomer) Sal003 Azoramide BTdCPU CCT020312 AMG PERK 44 MK-28

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID
human A549 cells	Function assay		1 h		Inhibition of thapsigargin-induced autophosphorylation of PERK in human A549 cells preincubated for 1 hr followed by thapsigargin-induction measured after 1 hr by Western blotting analysis, IC50=0.03 μM	24900593
Click to View More Cell Line Experimental Data

Solubility

In vitro
Batch:

DMSO : 10.3 mg/mL (24.73 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 10 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

% Tween 80

% ddH₂O

% DMSO

Calculation results:

Working concentration: mg/ml;

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.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Chemical Information, Storage & Stability

Molecular Weight	416.45	Formula	C₂₃H₂₁FN₆O	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1337532-29-2	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	CC1=NC(=CC=C1)CC(=O)N2CCC3=C2C=CC(=C3F)C4=CN(C5=NC=NC(=C45)N)C

Mechanism of Action

Features	Orally bioavailable PERK-selective inhibitor that functions independent of eIF2α phosphorylation.
Targets/IC₅₀/Ki	PERK (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 this compound 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 this chemical. In the absence of exogeneous UPR inducers, this compound has no significant effect on the growth of any of these cells with IC₅₀ range of 6–25 mM. Thus, this compound can be used to evaluate the biologic function of PERK in various biologic contexts.
Kinase Assay	Kinase assay
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 of this compound is evaluated using 27 kinases at GSK as well as a panel of 300 kinases.
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 this compound 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 this chemical results in inhibition of tumor growth in multiple human tumor xenografts.
References	[1] https://pubmed.ncbi.nlm.nih.gov/23333938/

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