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509584 ISR Inhibitor, ISRIB - CAS 1597403-47-8 - Calbiochem

The cell-permeable, selective inhibitor of eIF2α/eIF2S1 Ser51 phosphorylation-initiated UPR response (~25 to 200 nM) upon ER stress induction.

MSDS (material safety data sheet) or SDS, CoA and CoQ, dossiers, brochures and other available documents.

Synonyms: trans-2-(4-Chlorophenoxy)-N-(4-(2-(4-chlorophenoxy)acetylamino)cyclohexyl)acetamide, Integrated Stress Response Inhibitor, UPR Inhibitor, eIF2α (pS51) Signaling Inhibitor, eIF2S1 (pS51) Signaling Inhibitor

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509584
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Overview

Replacement Information

Key Specifications Table

CAS #Empirical Formula
1597403-47-8C₂₂H₂₄Cl₂N₂O₄

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      Description
      OverviewThe cell-permeable trans diastereomer of a bis-glycolamide compound that acts as a potent and selective blocker of eIF2α/eIF2S1 Ser51 phosphorylation-initiated unfold protein response/UPR (Effec. conc. 25 to 200 nM in HEK293T, HeLa, MEF, U2OS cultures) upon ER stress induction. Although noncytotoxic in the absence of ER stress, ISRIB does cause enhanced apoptotic cell death upon ER stress induction by Thapsigargin/Tg (100 to 500 nM; Cat. Nos. 586005 & 586006) or Tunicamycin/Tm (2 to 5 µg/mL; Cat. No. 654380) treatment. Reported to exhibit good pharmacokinetics with blood-brain permeability in mice and significantly enhance learning and long-term memory in mice (0.25 mg/kg/d i.p.) and rats (25 ng/0.5 µL/275-350 g rat; amygdala administration via cannulation) in vivo. Although the exact molecular target is not yet established, ISRIB most likely exerts its effect by modulating the interaction between the guanine nucleotide exchange factor eIF2B and the phosphorylated eIF2α (pS51).
      Catalogue Number509584
      Brand Family Calbiochem®
      Synonymstrans-2-(4-Chlorophenoxy)-N-(4-(2-(4-chlorophenoxy)acetylamino)cyclohexyl)acetamide, Integrated Stress Response Inhibitor, UPR Inhibitor, eIF2α (pS51) Signaling Inhibitor, eIF2S1 (pS51) Signaling Inhibitor
      References
      ReferencesSidrauski, C., et al. 2013 Elife 2, e00498.
      Product Information
      CAS number1597403-47-8
      FormLight beige powder
      Hill FormulaC₂₂H₂₄Cl₂N₂O₄
      Chemical formulaC₂₂H₂₄Cl₂N₂O₄
      ReversibleY
      Structure formula ImageStructure formula Image
      Quality LevelMQ100
      Applications
      Biological Information
      Purity≥93% by HPLC
      Physicochemical Information
      Cell permeableY
      Dimensions
      Materials Information
      Toxicological Information
      Safety Information according to GHS
      Safety Information
      Product Usage Statements
      Storage and Shipping Information
      Ship Code Ambient Temperature Only
      Toxicity Standard Handling
      Storage +2°C to +8°C
      Protect from Light Protect from light
      Do not freeze Ok to freeze
      Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
      Packaging Information
      Packaged under inert gas Packaged under inert gas
      Transport Information
      Supplemental Information
      Specifications
      Global Trade Item Number
      Catalog Number GTIN
      5.09584.0001 04055977240979

      Documentation

      ISR Inhibitor, ISRIB - CAS 1597403-47-8 - Calbiochem SDS

      Title

      Safety Data Sheet (SDS) 

      References

      Reference overview
      Sidrauski, C., et al. 2013 Elife 2, e00498.
      Data Sheet

      Note that this data sheet is not lot-specific and is representative of the current specifications for this product. Please consult the vial label and the certificate of analysis for information on specific lots. Also note that shipping conditions may differ from storage conditions.

      Revision21-February-2014 JSW
      Synonymstrans-2-(4-Chlorophenoxy)-N-(4-(2-(4-chlorophenoxy)acetylamino)cyclohexyl)acetamide, Integrated Stress Response Inhibitor, UPR Inhibitor, eIF2α (pS51) Signaling Inhibitor, eIF2S1 (pS51) Signaling Inhibitor
      DescriptionThe cell-permeable trans-diastereomer of a bis-glycolamide compound that acts as a potent and selective blocker ofeIF2α/eIF2S1-Ser51 phosphorylation-initiated unfold protein response/UPR (Effec. conc. 25 to 200 nM in HEK293T, HeLa, MEF, U2OS cultures) upon ER stress induction by Cys/Met starvation, HRI activation (6 µM KM09748), Thapsigargin/Tg (100 to 500 nM; Cat. Nos. 586005 & 586006) or Tunicamycin/Tm (2 to 5 µg/mL; Cat. No. 654380) treatment without affecting UPR responses independent of eIF2α (pS51), including ATF6 cleavage and IRE1-initiated XBP1s production. Although noncytotoxic in the absence of ER stress, ISRIB does prevent URP from properly restoring ER homeostasis following ER stress induction, causing enhanced apoptotic cell death in Tg- or Tm-treated HEK293T (2 µg/mL Tm & 200 nM ISRIB) and HeLa (25 nM ISRIB and 5 µg/mL Tm or 500 nM Tg) cultures. Reported to exhibit good pharmacokinetics with blood-brain permeability (plasma/brain Tmax ≈ 6/6 h; Cmax ≈ 180/100 ng/mL; C24 h ≈ 55/33 ng/mL; 2.5 mg/kg i.p.) in mice and significantly enhance hippocampus-dependent learning of mice subjected to Morris water maze (0.25 mg/kg/d i.p.) in vivo. Likewise, single amygdala administration via cannulation (25 ng/0.5 µL/275-350 g rat) immediately following auditory fear conditioning significantly enhances long-term, but not short-term, post-conditioning auditory response (% response above basal at 4 h/24 post conditioning = 27/33 vs. 27/22 among vehicle-treated control rats) in rats in vivo. Although the exact molecular target is not yet established, ISRIB most likely exerts its effect by modulating the interaction between the guanine nucleotide exchange factor eIF2B and the phosphorylated eIF2α (pS51).
      FormLight beige powder
      Intert gas (Yes/No) Packaged under inert gas
      CAS number1597403-47-8
      Chemical formulaC₂₂H₂₄Cl₂N₂O₄
      Structure formulaStructure formula
      Purity≥93% by HPLC
      SolubilityDMSO (10 mg/ml)
      Storage Protect from light
      +2°C to +8°C
      Do Not Freeze Ok to freeze
      Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
      Toxicity Standard Handling
      ReferencesSidrauski, C., et al. 2013 Elife 2, e00498.