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    ISRIB (trans-isomer)
    ISRIB (trans-isomer)

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    InvivoChem Cat #: V0061
    CAS #: 1597403-47-8 (trans-ISRIB)Purity ≥98%

    Description: ISRIB, the trans-isomer of ISRIB, is a novel, potent and selective inhibitor of PERK (PRKR-like endoplasmic reticulum kinase or protein kinase R (PKR)-like endoplasmic reticulum kinase) with IC50 of 5 nM. ISRIB reversed the effects of eIF2α phosphorylation with IC50 value of 5 nM. ISRIB inhibited production of endogenous ATF4 (a cAMP element binding transcription factor). In mouse embryonic fibroblasts (MEFs), ISRIB reversed the increase in the 80S monosomes at the expense of polyribosomes induced by endoplasmic reticulum (ER) stress. In ER-stressed cells, ISRIB reduced cell survival. In stressed cells, ISRIB restored mRNA translation and inhibited stress granule (SG) formation induced by eIF2α phosphorylation.

    References: Science. 2015 May 29;348(6238):1027-30; Elife. 2015 Apr 15;4:e07314.

    Related CAS: 548470-11-7 (cis-isomer)  

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    Molecular Weight (MW)451.34
    FormulaC22H24Cl2N2O4
    CAS No.1597403-47-8
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 4 mg/mL (8.86 mM)
    Water: <1 mg/mL (slightly soluble or insoluble)
    Ethanol: <1 mg/mL
    SynonymISRIB; trans-ISRIB;
    Chemical Nametrans-N,N'-(cyclohexane-1,4-diyl)bis(2-(4-chlorophenoxy)acetamide)


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    In Vitro

    Kinase Assay: High-content microscopy-based secondary screen; U2OS cells carrying the ATF4-dGFP-IRES-Cherry reporter are plated in 96 well plates and treated with 100 nM Thapsigargin and 10μM of the cherry-picked compounds for 8 hr. Cells are stained with Hoechst 33,258 and are visualized using an automated microscope. Data acquisition and image analyses are performed with the INCell Developer Toolbox Software, version 1.9. Compounds that block induction of the ATF4-dGFP reporter, do not block the accumulation of mCherry downstream of the IRES, and are deemed non-toxic as determined by cell number measured by counting nuclei, are repurchased for further analyses.


    Cell Assay: ISRIB blocks production of endogenous ATF4, whereas XBP1 mRNA splicing and XBP1s production persisted. ISRIB prevents cells from re-establishing ER homeostasis by blocking signaling through the PERK branch of the UPR, and decreases the viability of cells that are subjected to ER-stress.

    In VivoISRIB shows favorable properties in pharmacokinetic profiling experiments and good bioavailability in vivo. ISRIB (0.25 mg/kg i.p.) increases long-term memory in mice by enhancing spatial and fear-associated learning.
    Animal modelMale C57BL/6J mice
    Formulation & Dosage Saline, 1% DMSO; 0.25 mg/kg; i.p.
    References[1] Sidrauski C, et al. Elife. 2013, 2, e00498.


    These protocols are for reference only. InvivoChem does not independently validate these methods.

     

    ISRIB (trans-isomer)

    ISRIB (trans-isomer)Sidrauski C, et al. Elife. 2013, 2, e00498.
     

    ISRIB (trans-isomer)

    ISRIB enhances spatial and fear-associated learning in rodents. Sidrauski C, et al. Elife. 2013, 2, e00498.


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