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ISRIB

Catalog No.
B6093
PERK signaling inhibitor
Grouped product items
SizePriceStock Qty
5mg
$60.00
In stock
25mg
$235.00
In stock
For scientific research use only and should not be used for diagnostic or medical purposes.

Tel: +1-832-696-8203

Email: [email protected]

Worldwide Distributors

Background

ISRIB (CAS: 548470-11-7) is a potent inhibitor of PERK-mediated signaling, one of the four mammalian eIF2α kinases activated upon accumulation of misfolded proteins in the endoplasmic reticulum (ER). ISRIB selectively inhibits downstream signaling of PERK without significantly affecting the XBP1 splicing or ATF6 activation pathways of the unfolded protein response. It has an IC50 of approximately 5 nM in vitro and exhibits stereospecific potency, with trans-ISRIB surpassing cis-ISRIB by a factor of 100. Preclinical studies show ISRIB crosses the blood-brain barrier, enhances cognitive performance in murine learning assays, and holds potential for studying cognitive dysfunction.

Product Citation

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt451.34
Cas No.548470-11-7
FormulaC22H24Cl2N2O4
Solubilityinsoluble in H2O; insoluble in EtOH; ≥15.03 mg/mL in DMSO with gentle warming
Chemical Name(1Z,1'Z)-N',N''-((1r,4r)-cyclohexane-1,4-diyl)bis(2-(4-chlorophenoxy)acetimidic acid)
SDFDownload SDF
Canonical SMILESClC1=CC=C(OC/C(O)=N/[C@@]2([H])CC[C@@](/N=C(O)/COC3=CC=C(Cl)C=C3)([H])CC2)C=C1
Shipping ConditionSmall Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips We do not recommend long-term storage for the solution, please use it up soon.

Protocol

Cell experiment:[1]

Cell lines

HEK293T cells

Reaction Conditions

200 nM ISRIB for 24 h incubation

Applications

Addition of ISRIB alone did not affect cell viability, but caused a strong synergistic effect on ER-stressed cells, reducing colony number and size significantly more than ER-stress alone. This reduction in cell survival resulted from activation of apoptosis as the activity of the executioner caspases 3 and/or 7 was significantly induced under these conditions. Thus, ISRIB could synergize with ER stress to induce apoptosis.

Animal experiment:[1]

Animal models

Eight to ten-week-old male C57BL/6J mice

Dosage form

0.25 mg/kg

Injected intraperitoneally

Applications

In a Morris water maze, ISRIB-treated mice reached the hidden platform significantly faster compared to vehicle treated controls. The difference was already pronounced by days 3 and 4.

Note

The technical data provided above is for reference only.

References:

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

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