ISRIB
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.
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 451.34 |
Cas No. | 548470-11-7 |
Formula | C22H24Cl2N2O4 |
Solubility | insoluble 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) |
SDF | Download SDF |
Canonical SMILES | ClC1=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 Condition | Small 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. |
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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