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ISRIB (trans-isomer) PERK inhibitor

Name: ISRIB (trans-isomer)
Brand: Selleck Chemicals
SKU: S7400
Availability: InStock
Rating: 5 (8 reviews)

Cat.No.S7400

ISRIB (trans-isomer) is a potent and selective PERK inhibitor with IC50 of 5 nM and does not have global effects on translation, transcription, or mRNA stability in non-stressed cells.

Chemical Structure

Molecular Weight: 451.34

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Quality Control

Batch: Purity: 99.87%

99.87

Related Targets	Bcl-2 Caspase K-Ras PD-1/PD-L1 Ferroptosis p53 Apoptosis related Synthetic Lethality STAT TNF-alpha
Other PERK Inhibitors	GSK2606414 GSK2656157 Salubrinal Sal003 Azoramide BTdCPU CCT020312 AMG PERK 44 MK-28

Solubility

In vitro
Batch:

DMSO : 5 mg/mL (11.07 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : 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.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.100mg/ml (0.22mM)	Taking the 1 mL working solution as an example, add 50 μL of 2 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
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	451.34	Formula	C₂₂H₂₄Cl₂N₂O₄	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1597403-47-8	--		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	C1CC(CCC1NC(=O)COC2=CC=C(C=C2)Cl)NC(=O)COC3=CC=C(C=C3)Cl

Mechanism of Action

Targets/IC₅₀/Ki	PERK (Cell-free assay) 5 nM
In vitro	ISRIB (trans-isomer) blocks production of endogenous ATF4, whereas XBP1 mRNA splicing and XBP1s production persisted. It prevents cells from re-establishing ER homeostasis by blocking signaling through the PERK branch of the UPR, and decreases the viability of cells that are subjected to ER-stress.
Kinase Assay	High-content microscopy-based secondary screen
Kinase Assay	U2OS cells carrying the ATF4-dGFP-IRES-Cherry reporter are plated in 96 well plates and treated with 100 nM Thapsigargin and 10μM of the cherry-picked compounds for 8 hr, including ISRIB (trans-isomer). Cells are stained with Hoechst 33,258 and are visualized using an automated microscope. Data acquisition and image analyses are performed with the INCell Developer Toolbox Software, version 1.9. Compounds that block induction of the ATF4-dGFP reporter, do not block the accumulation of mCherry downstream of the IRES, and are deemed non-toxic as determined by cell number measured by counting nuclei, are repurchased for further analyses.
In vivo	ISRIB (trans-isomer) shows favorable properties in pharmacokinetic profiling experiments and good bioavailability in vivo. This compound (0.25 mg/kg i.p.) increases long-term memory in mice by enhancing spatial and fear-associated learning.
References	[1] https://pubmed.ncbi.nlm.nih.gov/23741617/

Applications

Methods	Biomarkers	Images	PMID
Western blot	PERK / XBP1s / ATF4		23741617

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