ISRIB (trans-isomer) is a potent inhibitor of PERK (IC50=5 nM) that restores protein translation and prevents SG formation in the presence of P-eIF2α.

PERK:5 nM

METHODS: HEK293T cells were treated with clindamycin (2 µg/mL) to induce ER stress and with ISRIB (trans-isomer) or ISRIB (cis-isomer) (0-1 µM) for 7 h. The ATF4 fluorokinase reporter gene was detected.
RESULTS: ISRIB (trans-isomer) was 100-fold more potent (IC50=5 nM) than ISRIB (cis-isomer) (IC50=600 nM), suggesting that the compound interacts stereospecifically with its cellular target. [1]
METHODS: HEK293T cells were treated with Tm (1 µg/mL) and ISRIB (200 nM) for 1 h. Translation and mRNA changes were detected.
RESULTS: ISRIB completely blocked the translational changes that occurred under ER stress. A large number of genes with significant changes in expression upon stress collapsed to the center of the graph under ISRIB and Tm co-treatment. [2]

METHODS: To investigate the effects on memory, ISRIB (0.25-2.5 mg/kg) was administered intraperitoneally to CD-1 mice.
RESULTS: ISRIB-treated mice showed significant enhancement in spatial and fear-related learning. [1]

U2OS cells are plated on 96-well plates and left to recover overnight. Cells are treated with either with 2 μg/ml tunicamycin or 100 nM thapsigargin in the presence or absence of 100 nM ISRIB or with ISRIB alone for the indicated and the level of eIF2α phosphorylation is determined[1].