ISR inhibitor (small molecule)

Integrated stress response (ISR) inhibitors are small molecule therapeutics designed to modulate the ISR, a conserved intracellular signaling pathway activated in response to various environmental and physiological stressors (such as endoplasmic reticulum stress, nutrient deprivation, viral infection, and oxidative stress). Chronic or aberrant activation of the ISR is implicated in the pathogenesis of several neurodegenerative and neuroinflammatory disorders, including multiple sclerosis (MS), Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and vanishing white matter disease (VWMD). Small molecule ISR inhibitors, such as ISRIB and its derivatives, typically act as activators of eukaryotic translation initiation factor 2B (eIF2B), reversing the translational repression caused by eukaryotic translation initiation factor 2 subunit alpha (eIF2α) phosphorylation. By restoring global protein synthesis and preventing stress granule formation, these inhibitors protect synapses, promote oligodendrocyte survival, and improve neurological and visual functions in preclinical models of demyelinating diseases.

Other names

ISR inhibitorintegrated stress response inhibitorsmall molecule ISR inhibitor