ISRIB
≈ 2 min read
Names in other languages
No names in other languages are held for this entry yet.
Article bodies are English and are not machine-translated. A name in another language is not a translation of the article.
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.
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 IC 50 of 5 nM. It has been shown to inhibit eIF2α phosphorylation-induced stress granule (SG) formation.
Further refinement and clinical development
The technology was licensed to Calico in 2015 and Sidrauski was hired to help find possible drugs based on ISRIB. She heads the laboratory in which it is being studied. Calico partnered with Abbvie to create fosigotifator based on ISRIB and the companies began to develop fosigotifator for amyotrophic lateral sclerosis (ALS) and major depressive disorder. In January 2025 Abbott and Calico announced that the drug had failed a Phase 2/3 trial in ALS; in July 2025 Abbott ended its partnership with Calico.
Text derived from https://en.wikipedia.org/w/index.php?oldid=1365843320 under CC BY-SA 4.0; modifications have been made.