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An integrated stress response (ISR) inhibitor that promotes survival of pluripotent stem cells in culture when used in combination with Chroman 1 and Emricasan small molecules in the CEPT cocktail1.
Trans-ISRIB (ISRIB trans-isomer) is an integrated stress response (ISR) inhibitor that acts downstream of PERK to target interactions between eIF2α and eIF2B, potently reversing the effects of eIF2α phosphorylation. Trans-ISRIB restores cells’ translation capacity by substantially reversing the translational effects elicited by phosphorylation of eIF2α and induces no major changes in translation or mRNA levels in unstressed cells. eIF2α phosphorylation-induced stress granule (SG) formation is blocked by ISRIB.2
Trans-ISRIB is 100-fold more potent (IC50 = 5 nM) than cis-ISRIB (IC50 = 600 nM), indicating that the compound’s interaction with its cellular target is stereospecific.
Trans-ISRIB promotes survival of dissociated pluripotent stem cells in culture when used in combination with Chroman 1 and Emricasan small molecules in the CEPT cocktail.1 Trans-ISRIB is a component of Captivate Bio's CET Cocktail.
Alternative names: ISRIB (trans-isomer) Applications: Stem Cell Survival, CEPT Cocktail, IRS Inhibitor, Cell Translation Cell types: Neurons, Pluripotent Stem Cells, iPSCs, ESCs
The data provided herein may relate to products or workflows that have not been fully validated by Captivate Bio and is subject to change without notice.
Keywords: Trans-ISRIB, ISRIB (trans isomer), ISRIB, PERK, apoptosis, autophagy, PRK-like endoplasmic reticulum kinase, CEPT, pluripotent, stem cell, self-renewal, proliferation, cell recovery, cryopreservation, cloning, single cell stress memory, neuroscience
When used to enhance hPSC survival and clonal expansion during passaging, Trans-ISRIB is used at a final concentration of 0.7 µM in cell culture media. Trans-ISRIB is generally added to culture media at passaging and is removed during the first feeding the following day, and is used in combination with synergistic small molecule compounds (Chroman 1 and Emricasan) and a polyamine solution, known as the CEPT cocktail, to improve survival of dissociated cells. See Chen et al. 2021 for more information on CEPT application and dosing for improved hPSC survival.
Trans-ISRIB is soluble in DMSO to 5 mg/mL (approx. 11 mM). Gentle warming (40°C to 60°C) and sonication may be needed for complete solubilization.
Trans-ISRIB restores cells’ translation capacity by substantially reversing the translational effects elicited by phosphorylation of eIF2α and induces no major changes in translation or mRNA levels in unstressed cells. eIF2α phosphorylation-induced stress granule (SG) formation is blocked by ISRIB.Trans-ISRIB helps cells continue translation, which is normally compromised when cells are stressed, especially in such cases as single-cell dissociation of hPSCs.
Trans-ISRIB, also known as ISRIB trans-isomer, is an integrated stress response (ISR) inhibitor that acts downstream of PERK to target interactions between eIF2α and eIF2B, potently reversing the effects of eIF2α phosphorylation.When used in combination with Chroman 1, Emricasan, and polyamines (a combination known as CEPT), Trans-ISRIB improves human pluripotent stem cell survival, clonogenicity, EB and organoid formation, and viability of pluripotent and differentiated cells following cryopreservation. (Chen et al. Nature Methods 2021).
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This research spotlight highlights the superior cryoprotective capacity of the CEPT method and the survival and functionality of preserved hPSCs.
