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ISRIB (trans-isomer)

Catalog No.
PERK inhibitor,potent and selective
Grouped product items
SizePriceStock Qty
10mM (in 1mL DMSO)
In stock
In stock
In stock

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ISRIB (trans-isomer) is a potent inhibitor of the integrated stress response (ISR) [1].

Integrated stress response (ISR) is activated by diverse cellular conditions and rapidly reduces overall protein synthesis while enhancing translation of specific transcripts that support adaptive stress responses. The ISR is mediated by diverse stress-sensing kinases that phosphorylating serine 51 in eukaryotic translation initiation factor alpha (eIF2α) [2].

ISRIB (trans-isomer) is a potent ISR inhibitor. ISRIB reversed the effects of eIF2α phosphorylation with IC50 value of 5 nM. ISRIB inhibited production of endogenous ATF4 (a cAMP element binding transcription factor). In mouse embryonic fibroblasts (MEFs), ISRIB reversed the increase in the 80S monosomes at the expense of polyribosomes induced by endoplasmic reticulum (ER) stress. In ER-stressed cells, ISRIB reduced cell survival [1]. In stressed cells, ISRIB restored mRNA translation and inhibited stress granule (SG) formation induced by eIF2α phosphorylation [2]. ISRIB inhibited the interaction between eIF2B and eIF2 that located at the core of the ISR [3]. Also, ISRIB was an activator of eIF2B and stabilized activated eIF2B dimers [4].

In mice, ISRIB significantly increased hippocampus-dependent spatial and fear-associated learning [1].

[1].  Sidrauski C, Acosta-Alvear D, Khoutorsky A, et al. Pharmacological brake-release of mRNA translation enhances cognitive memory. Elife, 2013, 2: e00498.
[2].  Sidrauski C, McGeachy AM, Ingolia NT, et al. The small molecule ISRIB reverses the effects of eIF2α phosphorylation on translation and stress granule assembly. Elife, 2015, 4.
[3].  Sekine Y, Zyryanova A, Crespillo-Casado A, et al. Stress responses. Mutations in a translation initiation factor identify the target of a memory-enhancing compound. Science, 2015, 348(6238): 1027-1030.
[4].  Sidrauski C, Tsai JC, Kampmann M, et al. Pharmacological dimerization and activation of the exchange factor eIF2B antagonizes the integrated stress response. Elife, 2015, 4: e07314.

Product Citation

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
Cas No.1597403-47-8
Solubilityinsoluble in EtOH; insoluble in H2O; insoluble in EtOH; ≥8.96 mg/mL in DMSO with gentle warming
Chemical NameN,N'-((1s,4s)-cyclohexane-1,4-diyl)bis(2-(4-chlorophenoxy)acetamide)
SDFDownload SDF
Shipping ConditionShip with blue ice, or upon other requests.
General tipsFor obtaining a higher solubility, please warm the tube at 37°C and shake it in the ultrasonic bath for a while. We do not recommend long-term storage for the solution, please use it up soon.


Cell experiment [1]:

Cell lines

ER-stressed cells

Preparation method

The solubility of this compound in DMSO is >4.5 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

200 nM, 24 hr


ISRIB (trans-isomer) inhibited the ATF4-luciferase reporter with the IC50 of 5 nM. ISRIB (200 nM) blocked production of endogenous ATF4 in ER-stressed U2OS cells. ISRIB reduced the viability of cells subjected to PERK-activation by chronic endoplasmic reticulum stress. ISRIB (200 nM) sensitized HEK293T cells to acute ER stress. In Hela cells, ISRIB (25 nM) synergized with ER stress to activate caspase 3/7. In HEK293Trex cells carrying an inducible FLAG epitope-tagged ATF6, ATF6 cleavage was sustained in ER-stressed cells treated with ISRIB.

Animal experiment [1]:

Animal models

Female CD-1 mice, male C57BL/6J mice

Dosage form

Intraperitoneal injection, 5 mg/kg


ISRIB-treated mice displayed significant enhancement in spatial and fear-associated learning. In female CD-1 mice, ISRIB (5 mg/kg) displayed a half-life in plasma of 8 hr and readily crossed the blood-brain barrier, quickly equilibrating with the central nervous system. In male C57BL/6J mice, systemic administration of ISRIB (intraperitoneally, 2.5 mg/kg) enhanced long-term contextual fear memory. ISRIB enhanced auditory fear conditioning in male Sprague Dawley rats.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.


[1]. Sidrauski C, Acosta-Alvear D, Khoutorsky A, et al. Pharmacological brake-release of mRNA translation enhances cognitive memory[J]. Elife, 2013, 2: e00498.

Biological Activity

Description ISRIB (trans-isomer), the trans-isomer of ISRIB, is a potent and selective inhibitor of PERK with IC50 of 5 nM.
Targets PERK          
IC50 5 nM          

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