Integrated stress response inhibitor / Integrated stress response inhibitor. Potently reverses the effects of initiation factor 2α (eIF2α) phosphorylation, IC50=5 nM.1 Enhances spatial and fear-associated learning in mice and enhances cognitive function.1,2 Mechanism of action involves activation of eiF2β.3 Suppresses ER stress-induced inflammatory gene expression.4 Potently attenuates amyloid β-induced neuronal cell death (12.5-25 nM) with no effect on amyloid β production.5 Reverses hippocampal-dependent cognitive deficits induced by traumatic brain injury in two different injury mouse models.6
Biochemicals & reagents
1597403-47-8
trans-ISRIB
1) Sidrauski et al. (2013), Pharmacological brake-release of mRNA translation enhances cognitive memory; Elife, 2 e00498 2) Sekine et al. (2015), Stress responses. Mutations in a translation initiation factor identify the target of a memory-enhancing compound; Science, 348 1027 3) Sidrauski et al. (2015), Pharmacological dimerization and activation of the exchange factor eIF2B antagonizes the integrated stress response; Elife, 4 e07314 4) Guthrie et al. (2016), Attenuation of PKR-like ER Kinase (PERK) Signaling Selectively Controls Endoplasmic Reticulum Stress-Induced Inflammation Without Compromising Immunological Responses; J. Biol. Chem., 291 15830 5) Hosoi et al. (2016), Unique pharmacological property of ISRIB in inhibition of Aβ-induced neuronal cell death; J. Pharmacol. Sci., 131 292 6) Chou et al. (2017), Inhibition of the integrated stress response reverses cognitive deficits after traumatic brain injury; Proc. Natl. Acad. Sci. USA, 114 E6420
-20°C
TARGET: Ribosome; ER/Golgi; UPR (Unfolded protein response) -- PATHWAY: Protein synthesis; Mitochondrial function -- RESEARCH AREA: Neuroscience; Ubiquitin/Proteasome -- DISEASE AREA: Inflammation; NeurodegenerationAgeing; Osteoporosis