ISRIB (trans-isomer)

ISRIB (trans-isomer) is a potent inhibitor of PERK with an IC₅₀ of 5 nM. ISRIB potently reverses the effects of eIF2α phosphorylation (IC₅₀=5 nM). IC50 & Target:IC50: 5 nM (PERK)^[1] In Vitro:Trans-ISRIB is 100-fold more potent (IC₅₀=5 nM) than cis-ISRIB (IC₅₀= 600 nM), indicating that the compound’s interaction with its cellular target is stereospecific. ISRIB reduces the viability of cells subjected to PERK-activation by chronic endoplasmic reticulum stress^[1]. ISRIB substantially reverses the translational effects elicited by phosphorylation of eIF2α and induces no major changes in translation or mRNA levels in unstressed cells. eIF2α phosphorylation-induced stress granule (SG) formation is blocked by ISRIB^[2]. In Vivo:ISRIB increases long-term memory in rodents. ISRIB-treated mice display significant enhancement in spatial and fear-associated learning. ISRIB displays a half-life in plasma of 8 hr and readily crossed the blood-brain barrier, quickly equilibrating with the central nervous system^[1].