trans-ISRIB

• CAT Number: I002023
• CAS Number: 1597403-47-8
• Molecular Formula: C22H24Cl2N2O4
• Molecular Weight: 451.344
• Purity: ≥95%
• Target: PERK
• Solubility: DMSO: ≥ 38 mg/mL
• Storage: Store at -20°C
• IC50: 5 nM [1]
• IUPAC Name: 2-(4-chlorophenoxy)-N-[4-[[2-(4-chlorophenoxy)acetyl]amino]cyclohexyl]acetamide
• InChI: InChI=1S/C22H24Cl2N2O4/c23-15-1-9-19(10-2-15)29-13-21(27)25-17-5-7-18(8-6-17)26-22(28)14-30-20-11-3-16(24)4-12-20/h1-4,9-12,17-18H,5-8,13-14H2,(H,25,27)(H,26,28)
• InChIKey: HJGMCDHQPXTGAV-UHFFFAOYSA-N
• SMILES: C1CC(CCC1NC(=O)COC2=CC=C(C=C2)Cl)NC(=O)COC3=CC=C(C=C3)Cl

ISRIB (trans-isomer) is a potent inhibitor of PERK signaling; inhibition of the ATF4 luciferase reporter in HEK293T cells with IC50 of 5 nM.IC50 value: 5 nM [1]Target: PERK inhibitorin vitro: Trans-ISRIB proved 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 blocked production of endogenous ATF4, whereas XBP1 mRNA splicing and XBP1s production persisted. ISRIB also did not affect activation of the ATF6-branch of the UPR. ISRIB blocks effects downstream of PERK and eIF2α phosphorylation [1].in vivo: ISRIB displayed a half-life in plasma of 8 hr and readily crossed the blood-brain barrier, quickly equilibrating with the central nervous system After a single intraperitoneal injection, we detected ISRIB in the brain of mice at concentrations several fold higher than its IC50 (24 hr after injection, the ISRIB concentration in the brain was approximately 60 nM). To explore ISRIB/’s effects on memory, we injected mice intraperitoneally with ISRIB and tested hippocampus-dependent spatial learning [1].

Reference

[1]. Sidrauski C, et al. Pharmacological brake-release of mRNA translation enhances cognitive memory. Elife. 2013 May 28;2:e00498.