ISRIB
Based on 28 publication(s) in Google Scholar
ISRIB is a brain-penetrant inhibitor of integrated stress response (ISR). Persistent activation of the ISR has been linked to the development of several neurological disorders as ISR represses translation through inhibiting eIF2B. ISRIB inhibits the ISR by promoting the nucleotide exchange activity of eIF2B and recovering the translation, and thus can be used for neurological disorders research.
For research use only. We do not sell to patients.
- Purity: 99.0%
- CAS No.: 548470-11-7
- Formula: C22H24Cl2N2O4
- Molecular Weight:451.34
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
Publications Citing Use of MedChemExpress (MCE) ISRIB
More- Nature. 2023 Sep;621(7977):188-195. [Abstract]
- Nat Commun. 2025 Jul 29;16(1):6972. [Abstract]
- Int J Oral Sci. 2024 May 8;16(1):35. [Abstract]
- Redox Biol. 2025 Dec:88:103905. [Abstract]
- Int J Biol Sci. 2024 Mar 25;20(6):2219-2235. [Abstract]
- Cell Death Dis. 2025 Jul 11;16(1):512. [Abstract]
- Cell Death Dis. 2024 Aug 1;15(8):552. [Abstract]
- Cell Commun Signal. 2023 Jun 29;21(1):167. [Abstract]
- J Transl Med. 2025 Aug 19;23(1):938. [Abstract]
- J Agric Food Chem. 2026 Mar 18;74(10):8671-8686. [Abstract]
- Biochem Pharmacol. 2026 Jun:248:117857. [Abstract]
- Biochem Pharmacol. 2024 Jun:224:116242. [Abstract]
- Chem Biol Interact. 2026 Mar 18:112045. [Abstract]
- Inflammation. 2025 Apr;48(2):747-759. [Abstract]
- Int Immunopharmacol. 2024 Aug 18:141:112950. [Abstract]
- J Virol. 2018 Jul 31;92(16). pii: e00600-18. [Abstract]
- Cell Signal. 2024 Nov:123:111353. [Abstract]
- Heliyon. 2024 Feb 23;10(5):e26904. [Abstract]
- Vet Microbiol. 2025 Jun 3:307:110559. [Abstract]
- Mol Biol Cell. 2024 Jun 1;35(6):br12. [Abstract]
- bioRxiv. 2026 May 31.
- bioRxiv. 2026 May 13:2026.05.11.724403. [Abstract]
- bioRxiv. 2026 Feb 18:2026.02.17.706363. [Abstract]
- bioRxiv. 2025 Sep 2.
- bioRxiv. 2025 August 27.
- bioRxiv. 2025 Aug 28.
- bioRxiv. 2025 May 1:2025.04.28.651077. [Abstract]
- Research Square Preprint. 2024 Mar 21.
Customer Validation & Images
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Histological Imaging/Staining
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RT-PCR
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WB
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Cell Proliferation/Viability Assay
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WB
Biological Activity
ISRIB (200 nM, 2 h) blocks stress granule formation induced by eIF2α phosphorylation in U2OS cells[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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CAS No. 548470-11-7
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Appearance Solid
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Molecular Weight 451.34
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Formula C22H24Cl2N2O4
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Color Off-white to light yellow
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SMILES
O=C(NC1CCC(NC(COC2=CC=C(Cl)C=C2)=O)CC1)COC3=CC=C(Cl)C=C3
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Publications (28)
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Journal Impact Factor
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Most Recent
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Nature
2023 Sep;621(7977):188-195. PMID: 37648854 -
Nat Commun
Autocrine interferon poisoning mediates ADAR1-dependent synthetic lethality in BRCA1/2-mutant cancers. [Abstract]2025 Jul 29;16(1):6972. PMID: 40730818 -
Int J Oral Sci
Phenformin activates ER stress to promote autophagic cell death via NIBAN1 and DDIT4 in oral squamous cell carcinoma independent of AMPK. [Abstract]2024 May 8;16(1):35. PMID: 38719825
ISRIB purchased from MedChemExpress. Usage Cited in: Int J Oral Sci. 2024 May 8;16(1):35. [Abstract]
Protein expression levels of ATF4, DDIT4, NIBAN1, p62, ATG5, and LC3-I/II were analyzed by Western blot in CAL 27 cells at 4 h after treatment with 1 mmol/L phenformin (Phen), 200 nmol/L ISRIB, or DMSO as a control.
ISRIB purchased from MedChemExpress. Usage Cited in: Int J Oral Sci. 2024 May 8;16(1):35. [Abstract]
CAL 27 cells were treated with 1 mmol/L phenformin (Phen) or with 200 nmol/L ISRIB or 1 μmol/L GSK2606414 or DMSO as a control. At 24 h, cells were collected and analyzed by the CCK-8 assay for cell viability.
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Redox Biol
Integrated stress response-mediated metabolic reprogramming drives hepatic stellate cell activation and liver fibrosis via the noncanonical EIF3d-ATF4-S100P signaling pathway. [Abstract]2025 Dec:88:103905. PMID: 41197183
ISRIB purchased from MedChemExpress. Usage Cited in: Redox Biol. 2025 Dec:88:103905. [Abstract]
Schematic illustrating ISRIB treatment regimen (20 mg/kg, administered twice weekly from weeks 4–8) in CCl4-induced fibrotic mouse models. (B) Representative images of HE staining in liver sections after CCl4 treatment.
ISRIB purchased from MedChemExpress. Usage Cited in: Redox Biol. 2025 Dec:88:103905. [Abstract]
Schematic illustrating ISRIB treatment regimen (20 mg/kg, administered twice weekly from weeks 4–8) in CCl4-induced fibrotic mouse models. Relative gene expression levels of ATF4 in liver tissues after CCl4 injection for 8 weeks (n = 4).
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Int J Biol Sci
NUP85 alleviates lipid metabolism and inflammation by regulating PI3K/AKT signaling pathway in nonalcoholic fatty liver disease. [Abstract]2024 Mar 25;20(6):2219-2235. PMID: 38617542 -
Cell Death Dis
IFNγ augments TKI efficacy by alleviating protein unfolding stress to promote GSDME-mediated pyroptosis in hepatocellular carcinoma. [Abstract]2025 Jul 11;16(1):512. PMID: 40645933 -
Cell Death Dis
Triggering of endoplasmic reticulum stress via ATF4-SPHK1 signaling promotes glioblastoma invasion and chemoresistance. [Abstract]2024 Aug 1;15(8):552. PMID: 39090107 -
Cell Commun Signal
Carbonic anhydrase IX inhibitor S4 triggers release of DAMPs related to immunogenic cell death in glioma cells via endoplasmic reticulum stress pathway. [Abstract]2023 Jun 29;21(1):167. PMID: 37386564 -
J Transl Med
Targeting ATF4-DDIT4/TXNIP induced mitochondrial dysfunction and ferroptosis: ISRIB as novel therapy for septic cardiomyopathy. [Abstract]2025 Aug 19;23(1):938. PMID: 40830971 -
J Agric Food Chem
Zearalenone Disrupts the Placental Barrier via Integrated Stress Response Activation in Mice and Human Trophoblast Cells. [Abstract]2026 Mar 18;74(10):8671-8686. PMID: 41780030 -
Biochem Pharmacol
Inhibition of mitochondrial integrated stress response ameliorates ibuprofen-induced endothelial dysfunction in neonatal hyperoxia-induced lung injury. [Abstract]2026 Jun:248:117857. PMID: 41780649 -
Biochem Pharmacol
ONC212 enhances YM155 cytotoxicity by triggering SLC35F2 expression and NOXA-dependent MCL1 degradation in acute myeloid leukemia cells. [Abstract]2024 Jun:224:116242. PMID: 38679209 -
Chem Biol Interact
Damage to newly synthesized proteins is a major cause of Cd(II) toxicity counteracted by proteasomes and integrated stress response in human cells. [Abstract]2026 Mar 18:112045. PMID: 41861982 -
Inflammation
Prenatal Inflammatory Exposure Predisposes Offspring to Chronic Kidney Diseases Via the Activation of the eIF2α-ATF4 Pathway. [Abstract]2025 Apr;48(2):747-759. PMID: 38913145 -
Int Immunopharmacol
Epigallocatechin gallate induces apoptosis in multiple myeloma cells through endoplasmic reticulum stress induction and cytoskeletal disruption. [Abstract]2024 Aug 18:141:112950. PMID: 39159563 -
J Virol
Porcine Reproductive and Respiratory Syndrome Virus Infection Induces both eIF2α Phosphorylation-Dependent and -Independent Host Translation Shutoff. [Abstract]2018 Jul 31;92(16). pii: e00600-18. PMID: 29899101
ISRIB purchased from MedChemExpress. Usage Cited in: J Virol. 2018 Jul 31;92(16). pii: e00600-18. [Abstract]
MARC-145 cells grown in six-well plates are treated with 0.5 mM Ars at 37°C for 1 h. The medium is changed to medium containing different concentrations of ISRIB and after 25 min, the cells are treated with puromycin, incubated at 37°C for 25 min, and lysed for western blotting analysis.
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Cell Signal
Unfolded proteins in the mitochondria activate HRI and inhibit mitochondrial protein translation. [Abstract]2024 Nov:123:111353. PMID: 39168261 -
Heliyon
eIF2α-mediated integrated stress response links multiple intracellular signaling pathways to reprogram vascular smooth muscle cell fate in carotid artery plaque. [Abstract]2024 Feb 23;10(5):e26904. PMID: 38434290 -
Vet Microbiol
PERK-mediated eIF2α phosphorylation suppresses porcine epidemic diarrhea virus replication by attenuating global protein synthesis and inducing IFN-Ⅰ production. [Abstract]2025 Jun 3:307:110559. PMID: 40494050 -
Mol Biol Cell
Baseline Unfolded Protein Response Signaling Adjusts the Timing of the Mammalian Cell Cycle. [Abstract]2024 Jun 1;35(6):br12. PMID: 38656789 -
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bioRxiv
Naked antisense oligonucleotides remain endolysosomally sequestered despite induced membrane damage. [Abstract]2026 May 13:2026.05.11.724403. PMID: 42182263 -
bioRxiv
Differential assembly of RNP granules via activation of distinct dsRNA sensors by adenovirus mutants. [Abstract]2026 Feb 18:2026.02.17.706363. PMID: 41756847 -
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bioRxiv
2025 May 1:2025.04.28.651077. PMID: 40655005 -
Solvent & Solubility
DMSO : 5.83 mg/mL (12.92 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
The following protocol is derived from the literature and is for reference only. It is recommended to first try a small sample.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Working solution concentration: 0.22 mg/mL
Purity & Documentation
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Data Sheet (270 KB)
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SDS (396 KB)
- English - EN (396 KB)
- Français - FR (396 KB)
- Deutsch - DE (396 KB)
- Norwegian - NO (396 KB)
- Español - ES (396 KB)
- Swedish - SV (396 KB)
- Italian - IT (396 KB)
- Korean - KR (396 KB)
- Portuguese - PT (396 KB)
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Handling Instructions (2659 KB)
References
[1]. Zyryanova AF, et al. ISRIB Blunts the Integrated Stress Response by Allosterically Antagonising the Inhibitory Effect of Phosphorylated eIF2 on eIF2B. Mol Cell. 2021 Jan 7;81(1):88-103.e6. [Content Brief]
[2]. Halliday M, et al. Partial restoration of protein synthesis rates by the small molecule ISRIB prevents neurodegeneration without pancreatic toxicity. Cell Death Dis. 2015 Mar 5;6(3):e1672. [Content Brief]
[3]. Sidrauski C, et al. The small molecule ISRIB reverses the effects of eIF2α phosphorylation on translation and stress granule assembly. Elife. 2015 Feb 26;4:e05033. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.2156 mL | 11.0781 mL | 22.1562 mL | 55.3906 mL |
| 5 mM | 0.4431 mL | 2.2156 mL | 4.4312 mL | 11.0781 mL | |
| 10 mM | 0.2216 mL | 1.1078 mL | 2.2156 mL | 5.5391 mL |
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