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Submit Reviewtrans-ISRIB
Description: Integrated stress response (ISR) inhibitor
Chemical Name: N,N'-trans-1,4-cyclohexanediylbis[2-(4-chlorophenoxy)acetamide]
Purity: ≥99% (HPLC)
Biological Activity for trans-ISRIB
trans-ISRIB is a potent integrated stress response (ISR) inhibitor; reverses the effects of eIF2α phosphorylation (IC50 = 5 nM) and restores cell translation capacity. Acts downstream of PERK, targeting interactions between eIF2α kinases and elF2B. Blocks ATF4 production without altering the IRE1 or ATF6 responses in vitro. Displays memory enhancement in hippocampus-dependent spatial and fear-associated learning in rodents. trans-ISRIB promotes survival of pluripotent stem cells in culture when used in combination with Chroman 1 (Cat. No. 7163), Emricasan (Cat. No. 7310), and Polyamine Supplement x1000 (lyophilized) (Cat. No. 7739), a combination known as CEPT. When used as part of the CEPT cocktail, trans-ISRIB improves survival of differentiated cells following cryopreservation. Brain penetrant.
Technical Data for trans-ISRIB
| M. Wt | 451.34 |
| Formula | C22H24Cl2N2O4 |
| Storage | Store at +4°C |
| Purity | ≥99% (HPLC) |
| CAS Number | 1597403-47-8 |
| PubChem ID | 1011240 |
| InChI Key | HJGMCDHQPXTGAV-UHFFFAOYSA-N |
| Smiles | O=C(COC1=CC=C(Cl)C=C1)N[C@@H]2CC[C@@H](NC(COC3=CC=C(Cl)C=C3)=O)CC2 |
The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.
Tocris products are intended for laboratory research use only, unless stated otherwise.
Solubility Data for trans-ISRIB
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 4.51 | 10 with gentle warming |
Preparing Stock Solutions for trans-ISRIB
The following data is based on the product molecular weight 451.34. Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 0.1 mM | 22.16 mL | 110.78 mL | 221.56 mL |
| 0.5 mM | 4.43 mL | 22.16 mL | 44.31 mL |
| 1 mM | 2.22 mL | 11.08 mL | 22.16 mL |
| 5 mM | 0.44 mL | 2.22 mL | 4.43 mL |
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Product Datasheets for trans-ISRIB
References for trans-ISRIB
References are publications that support the biological activity of the product.
Sidrauski et al (2013) Pharmacological brake-release of mRNA translation enhances cognitive memory. Elife 2 e00498 PMID: 23741617
Sekine et al (2015) Stress responses. Mutations in a translation initiation factor identify the target of a memory-enhancing compound. Science 348 1027 PMID: 25858979
Hinnebusch (2015) Cell biology. Blocking stress response for better memory? Science 348 967 PMID: 26023119
Chen et al (2021) A versatile polypharmacology platform promotes cytoprotection and viability of human pluripotent and differentiated cells. Nat.Methods 18 528 PMID: 33941937
If you know of a relevant reference for trans-ISRIB, please let us know.
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Keywords: trans-ISRIB, trans-ISRIB supplier, Potent, inhibitors, inhibits, of, PERK, signaling, UPR, unfolded, protein, response, endoplasmic, reticulum, ER, stress, memory, consolidation, eIF2, alpha, kinases, ISR, integrated, ISRIB, stem, cell, maintenance, self, renewal, pluripotent, CEPT, differentiated, cryo, DNA,, RNA, and, Protein, Synthesis, Miscellaneous, Compounds, Other, stress/UPR, Stem, Cell, Proliferation, Cocktail, 5284, Tocris Bioscience
14 Citations for trans-ISRIB
Citations are publications that use Tocris products. Selected citations for trans-ISRIB include:
Jeffrey D et al (2022) Polyadenylated RNA and RNA-Binding Proteins Exhibit Unique Response to Hyperosmotic Stress. Front Cell Dev Biol 9 809859 PMID: 34970554
Jason A et al (2022) Cis- and trans-resveratrol have opposite effects on histone serine-ADP-ribosylation and tyrosine induced neurodegeneration. Nat Commun 13 3244 PMID: 35688816
Jing et al (2022) Stress-induced perturbations in intracellular amino acids reprogram mRNA translation in osmoadaptation independently of the ISR. Cell Rep 40 111092 PMID: 35858571
Chen et al (2019) A versatile polypharmacology platform promotes cytoprotection and viability of human pluripotent and differentiated cells. Nat.Methods 18 528 PMID: 33941937
Gary W et al (2019) Adaptive Protein Translation by the Integrated Stress Response Maintains the Proliferative and Migratory Capacity of Lung Adenocarcinoma Cells. Mol Cancer Res 17 2343-2355 PMID: 31551255
Victor X et al (2019) The eIF2α Kinase GCN2 Modulates Period and Rhythmicity of the Circadian Clock by Translational Control of Atf4. Neuron 104 724-735.e6 PMID: 31522764
Jacques et al (2020) Saturated Fatty Acids Promote GDF15 Expression in Human Macrophages through the PERK/eIF2/CHOP Signaling Pathway. Nutrients 12 PMID: 33302552
Ryu et al (2023) Stress-free cell aggregation by using the CEPT cocktail enhances embryoid body and organoid fitness. Biofabrication 16 015016 PMID: 37972398
Lisa D et al (2023) A Ubiquitination Cascade Regulating the Integrated Stress Response and Survival in Carcinomas. Cancer Discov 13 766-795 PMID: 36576405
Tristan et al (2021) Robotic high-throughput biomanufacturing and functional differentiation of human pluripotent stem cells. Stem Cell Rep. 16 3076 PMID: 34861164
Krokowski (2017) GADD34 function in protein trafficking promotes adaptation to hyperosmotic stress in human corneal cells. Cell Rep. 21 2895 PMID: 29212034
Bo et al (2021) SARS-CoV-2 infection induces beta cell transdifferentiation. Cell Metab 33 1577-1591.e7 PMID: 34081913
Viviana et al (2021) Cholinergic neurons constitutively engage the ISR for dopamine modulation and skill learning in mice. Science 372 PMID: 33888613
Peter et al (2018) Coordination between Two Branches of the Unfolded Protein Response Determines Apoptotic Cell Fate. Mol Cell 71 629-636.e5 PMID: 30118681
Do you know of a great paper that uses trans-ISRIB from Tocris? Please let us know.
Reviews for trans-ISRIB
Average Rating: 5 (Based on 2 Reviews.)
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Inhibits integrated stress response in HEK293 cells.
By
mandi gandelman on 05/01/2019
Assay Type: In Vitro
Species: Human
Cell Line/Tissue: HEK293
Used trans-ISRIB to inhibit the integrated stress response (ISR) in HEK293 cells. Induced the ISR and added ISRIB (100 and 500nM) overnight. Evaluated p-eif2a (unchanged) and cleaved caspase 3 (increased in a dose-dependent manner with ISRIB.
High specific inhibitor.
By
Anonymous on 11/01/2017
Assay Type: In Vitro
Species: Rat
Cell Line/Tissue: cortical neurons
Toxicity assay. 500 nM concentration was used. Highly effective Integrated stress response (ISR) inhibitor. Works very well.
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Cell Cycle and DNA Damage Research Product Guide
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- Cell Cycle and Mitosis
- DNA Damage Repair
- Targeted Protein Degradation
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- Chemotherapy Targets