trans-ISRIB
Chemical Name: N,N'-trans-1,4-cyclohexanediylbis[2-(4-chlorophenoxy)acetamide]
Purity: ≥99%
Biological Activity
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
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.
Background References
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Pharmacological brake-release of mRNA translation enhances cognitive memory.
Sidrauski et al.
Elife, 2013;2:e00498 -
Stress responses. Mutations in a translation initiation factor identify the target of a memory-enhancing compound.
Sekine et al.
Science, 2015;348:1027 -
Cell biology. Blocking stress response for better memory?
Hinnebusch
Science, 2015;348:967
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Citations for trans-ISRIB
The citations listed below are publications that use Tocris products. Selected citations for trans-ISRIB include:
13 Citations: Showing 1 - 10
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A Ubiquitination Cascade Regulating the Integrated Stress Response and Survival in Carcinomas.
Authors: Lisa D Et al.
Cancer Discov 2023;13:766-795
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Polyadenylated RNA and RNA-Binding Proteins Exhibit Unique Response to Hyperosmotic Stress.
Authors: Jeffrey D Et al.
Front Cell Dev Biol 2022;9:809859
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Stress-induced perturbations in intracellular amino acids reprogram mRNA translation in osmoadaptation independently of the ISR.
Authors: Jing Et al.
Cell Rep 2022;40:111092
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Cis- and trans-resveratrol have opposite effects on histone serine-ADP-ribosylation and tyrosine induced neurodegeneration.
Authors: Jason A Et al.
Nat Commun 2022;13:3244
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Cholinergic neurons constitutively engage the ISR for dopamine modulation and skill learning in mice.
Authors: Viviana Et al.
Science 2021;372
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SARS-CoV-2 infection induces beta cell transdifferentiation.
Authors: Bo Et al.
Cell Metab 2021;33:1577-1591.e7
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Robotic high-throughput biomanufacturing and functional differentiation of human pluripotent stem cells.
Authors: Tristan Et al.
Stem Cell Rep. 2021;16:3076
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Saturated Fatty Acids Promote GDF15 Expression in Human Macrophages through the PERK/eIF2/CHOP Signaling Pathway.
Authors: Jacques Et al.
Nutrients 2020;12
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A versatile polypharmacology platform promotes cytoprotection and viability of human pluripotent and differentiated cells.
Authors: Chen Et al.
Nat.Methods 2019;18:528
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Adaptive Protein Translation by the Integrated Stress Response Maintains the Proliferative and Migratory Capacity of Lung Adenocarcinoma Cells.
Authors: Gary W Et al.
Mol Cancer Res 2019;17:2343-2355
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The eIF2α Kinase GCN2 Modulates Period and Rhythmicity of the Circadian Clock by Translational Control of Atf4.
Authors: Victor X Et al.
Neuron 2019;104:724-735.e6
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Coordination between Two Branches of the Unfolded Protein Response Determines Apoptotic Cell Fate.
Authors: Peter Et al.
Mol Cell 2018;71:629-636.e5
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GADD34 function in protein trafficking promotes adaptation to hyperosmotic stress in human corneal cells.
Authors: Krokowski
Cell Rep. 2017;21(10):2895
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