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EntityQ15409421· pop 7· linked from 4 articles

Also known as Integrated Stress Response inhibitor, trans-ISRIB

ISRIB (short for "integrated stress response inhibitor") is an experimental tool compound that blocks the integrated stress response, restoring the cell’s translation capacity. It showed promising results in mouse models of brain disorders but efforts to develop a drug based on it, had failed as of 2025.

Wikidata facts

Mass
450.11131260799993
Show 3 more facts
canonical SMILES
c1cc(ccc1OCC(=O)NC2CCC(CC2)NC(=O)COc3ccc(cc3)Cl)Cl
chemical formula
C₂₂H₂₄Cl₂N₂O₄
isomeric SMILES
O=C(COc1ccc(Cl)cc1)N[C@H]1CC[C@H](NC(=O)COc2ccc(Cl)cc2)CC1
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6 sections
Contents
  • Discovery
  • Mechanism of action
  • Preclinical work
  • Further refinement and clinical development
  • See also
  • References

ISRIB (short for "integrated stress response inhibitor") is an experimental tool compound that blocks the integrated stress response, restoring the cell’s translation capacity. It showed promising results in mouse models of brain disorders but efforts to develop a drug based on it, had failed as of 2025.

== Discovery== It was discovered by Carmela Sidrauski in the laboratory of Peter Walter at University of California, San Francisco (UCSF) through a semi-automated screening of a large library of small molecules seeking inhibitors of PERK signalling; it was found to block the integrated stress response when measured by eIF2α phosphorylation with an IC50 of 5 nM. It has been shown to inhibit eIF2α phosphorylation-induced stress granule (SG) formation.

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