ISRIB

Catalog No.S0706 Batch:S070602

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Technical Data

Formula
C22H24Cl2N2O4
Molecular Weight 451.34 CAS No. 548470-11-7
Solubility (25°C)* In vitro DMSO 23 mg/mL (50.95 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description ISRIB is an integrated stress response (ISR) inhibitor that potently reverses the effects of eukaryotic initiation factor 2α (eIF2α) phosphorylation.
Targets
ISR [1] eIF2α [1]
In vitro

ISRIB, an integrated stress response (ISR) inhibitor, reverses the effect of thapsigargin (TG) on translation, notably inhibits ER stress-induced cFLIP loss and prevents cFLIP levels down-regulation.[2]
In vivo

In an instability-induced intervertebral disc degeneration (IDD) model in mice, ISRIB suppressed p-eIF2α/ATF4/Ihh and prevented IDD via protecting the anti-oxidative enzymes and decreased the NP cell apoptosis.[3]

Protocol (from reference)

Cell Assay:

[2]
  • Cell lines

    HCT116 cells

  • Concentrations

    220 nM

  • Incubation Time

    1 h

  • Method

    HCT116 cells are pre-treated with ISRIB (220 nM) for 1 h prior TG treatment for the indicated times. To analyze protein synthesis, puromycin is added in the last 10 min of treatment and puromycin incorporation to the nascent protein chain is assessed by western blotting using an anti-puromycin antibody. Levels of both cFLIP isoforms are determined in whole cell extracts by western blotting and quantified.
Animal Study:

[3]
  • Animal Models

    C57 background BL/6J mice of intervertebral disc degeneration (IDD) models

  • Dosages

    0.25 mg/kg

  • Administration

    s.c.

Selleck's ISRIB has been cited by 18 publications

NAD+ dependent UPRmt activation underlies intestinal aging caused by mitochondrial DNA mutations [ Nat Commun, 2024, 15(1):546] PubMed: 38228611
Nucleus pulposus cells regulate macrophages in degenerated intervertebral discs via the integrated stress response-mediated CCL2/7-CCR2 signaling pathway [ Exp Mol Med, 2024, 56(2):408-421.] PubMed: 38316963
ERK mediates interferon gamma-induced melanoma cell death [ Mol Cancer, 2023, 10.1186/s12943-023-01868-x] PubMed: 37803324
Acute liver steatosis translationally controls the epigenetic regulator MIER1 to promote liver regeneration in a study with male mice [ Nat Commun, 2023, 14(1):1521] PubMed: 36934083
E3 ligase HECTD3 promotes RNA virus replication and virus-induced inflammation via K33-linked polyubiquitination of PKR [ Cell Death Dis, 2023, 14(7):396] PubMed: 37402711
E3 ligase HECTD3 promotes RNA virus replication and virus-induced inflammation via K33-linked polyubiquitination of PKR [ Cell Death Dis, 2023, 14(7):396] PubMed: 37402711
ETHE1 Accelerates Triple-Negative Breast Cancer Metastasis by Activating GCN2/eIF2α/ATF4 Signaling [ Int J Mol Sci, 2023, 24(19)14566] PubMed: 37834012
Neuron-specific translational control shift ensures proteostatic resilience during ER stress [ EMBO J, 2022, e110501] PubMed: 35791631
cFLIP downregulation is an early event required for endoplasmic reticulum stress-induced apoptosis in tumor cells [ Cell Death Dis, 2022, 13(2):111] PubMed: 35115486
Endoplasmic reticulum oxidoreductin 1-alpha deficiency and activation of protein translation synergistically impair breast tumour resilience [ Br J Pharmacol, 2022, 179(23):5180-5195] PubMed: 35853086

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.