ISRIB (trans-isomer) is a potent inhibitor of PERK with an IC50 of 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 interactionwith its cellular target is stereospecific. ISRIB reduces the viability of cells subjected to PERK-activation by chronic endoplasmic reticulum stress. ISRIB substantially reverses the translational effects elicited by phosphorylation of eIF2α and induces no majorchanges in translation or mRNA levels in unstressed cells. eIF2α phosphorylation-induced stress granule (SG) formation is blocked byISRIB.
In Vivo: ISRIB increases long-term memory in rodents. ISRIB-treated mice display significant enhancement in spatial and fearassociatedlearning. ISRIB displays a half-life in plasma of 8 hr and readily crossed the blood-brain barrier, quickly equilibrating with the central nervous system.