trans-ISRIB

trans-ISRIB is a potent, brain-penetrant small molecule that acts as a selective inhibitor of the integrated stress response (ISR). It functions as a positive allosteric modulator of the eukaryotic translation initiation factor 2B (eIF2B), a decameric complex essential for protein synthesis initiation. By stabilizing the active decameric form of eIF2B, trans-ISRIB renders the complex insensitive to the inhibitory effects of phosphorylated eIF2α, thereby restoring cellular translation during periods of stress. Discovered at the University of California, San Francisco, trans-ISRIB has shown significant efficacy in preclinical models for enhancing memory and treating conditions such as traumatic brain injury and neurodegenerative diseases. Although it served as the structural basis for clinical candidates like fosigotifator, trans-ISRIB itself remains a widely used research tool and is not an approved therapeutic.

Other names

ISRIBIntegrated Stress Response InhibitorN,N'-trans-1,4-cyclohexanediylbis[2-(4-chlorophenoxy)acetamide]