Trans Isrib CAS 1597403-47-8 high purity integrated stress response inhibitor compound for neurobiology research

CAS 1597403-47-8 Trans ISRIB Powder Selective ISR & PERK Inhibitor for Neurodegenerative Disease Research

 

Premium 99% Trans ISRIB crystalline powder CAS 1597403-47-8, potent selective PERK and integrated stress response inhibitor. Ideal for neuroprotection, cognitive enhancement and cellular stress response pharmacological research.
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Trans-ISRIB / ISRIB (CAS 1597403-47-8) | Integrated Stress Response Inhibitor & eIF2B Potentiator for Protein-Synthesis & Cognition Research

Trans-ISRIB (ISRIB, trans isomer) CAS 1597403-47-8
Integrated Stress Response (ISR) Inhibitor / eIF2B Potentiator — Protein-Synthesis & Neurocognition Research

Trans-ISRIB (ISRIB, trans isomer; CAS 1597403-47-8) is a potent inhibitor of the integrated stress response that potently activates eIF2B (the GEF for eIF2), restoring protein synthesis blocked by phosphorylated eIF2α. Molecular formula C18H18N2O2, MW 294.35. Research-grade with COA.

Trans-ISRIB ISRIB ISR Inhibitor eIF2B Protein Synthesis Integrated Stress Response Cognition Neurodegeneration
Request a Quote Technical Specs
294.35
MW (C18H18N2O2)
nM
eIF2B potentiation EC50
ISR+
Reverses eIF2α-P repression

Molecular Information

Name: Trans-ISRIB (ISRIB, trans isomer)
CAS: 1597403-47-8
Formula: C18H18N2O2
MW: 294.35 g/mol
Class: Bicyclic imidazolinone
Core: trans-(1,2,3,4-tetrahydro-1,4-dioxonaphthalene)-derived ISR scaffold
Target: eIF2B (eIF2 GEF)
Appearance: White to off-white solid
Synonyms: ISRIB (trans isomer)
Storage: -20 °C
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CAS Number
1597403-47-8
⚖️
Molecular Weight
294.35
🎯
Primary Activity
ISR Inhibitor / eIF2B Potentiator
✅
Purity
≥98%

Product Technical Specifications

Complete physicochemical properties and QC parameters for Trans-ISRIB (ISRIB, trans isomer) (CAS 1597403-47-8)

📋 Physicochemical Properties

  • Product NameTrans-ISRIB (ISRIB, trans isomer)
  • IUPAC Core(trans)-1,2,3,4-tetrahydro-1,4-dioxo-2,3-bis(4-methoxybenzyl)naphthalene-derived imidazolinone
  • CAS Number1597403-47-8
  • SynonymsISRIB (trans); trans-ISRIB
  • Molecular FormulaC18H18N2O2
  • Molecular Weight294.35 g/mol
  • SourceSynthetic small molecule
  • AppearanceWhite to off-white solid
  • Melting Point~230-232 °C (decomposition)
  • Water SolubilityVery low (<0.1 mg/mL)
  • Organic SolubilityDMSO ~10-30 mg/mL; ethanol (limited)
  • Compound ClassIntegrated stress response inhibitor (bicyclic imidazolinone)
  • HS Code2933.99

🔬 Quality Control & Handling

  • Purity (HPLC)≥98%
  • FormSolid powder
  • Primary TargeteIF2B (GEF for eIF2)
  • Pathway ReadoutRestores protein synthesis; ↓ ATF4/CHOP under ISR
  • SelectivityPotentiates eIF2B; counteracts eIF2α-P (not a kinase inhibitor)
  • Storage Condition-20 °C, sealed, protect from light
  • Solution StabilityAliquot DMSO stocks; avoid freeze-thaw
  • ShippingBlue ice / cold chain recommended
  • QC DocumentationCOA / HPLC / NMR / MS / MSDS
  • Pack Sizes1g / 5g / 10g / 100g / 1KG
  • Stock StatusIn Stock
  • Use StatementResearch use only; not for human/clinical use

Key Molecular Targets & Pathway Nodes

Trans-ISRIB targets eIF2B — the guanine-nucleotide-exchange factor for the translation-initiation factor eIF2. By potentiating eIF2B it bypasses the translational blockade imposed by phosphorylated eIF2α, the final common downstream node of the integrated stress response (ISR).

🧬 eIF2B (GEF for eIF2) 🧬 eIF2α (phosphorylated) 🧱 PERK / GCN2 / HRI / PKR (upstream ISR kinases) 🧬 Translation initiation 🧠 ATF4 / CHOP (ISR effectors) 🧠 Protein synthesis / ribosome 🔗 Integrated Stress Response (ISR) ⚡ Neuronal plasticity & memory

How Trans-ISRIB Works: Unblocking Translation by Activating eIF2B

Trans-ISRIB potently activates eIF2B, overriding eIF2α phosphorylation so protein synthesis and ISR gene programs are restored

1

ISR Blocks Translation via eIF2α-P

Under stress, kinases (PERK, GCN2, HRI, PKR) phosphorylate eIF2α. Phosphorylated eIF2α inhibits eIF2B — the GEF that recycles eIF2-GDP to active eIF2-GTP — so global translation initiation collapses and the ISR gene program (ATF4/CHOP) is switched on.

2

eIF2B Potentiation by Trans-ISRIB

Trans-ISRIB binds and allosterically potentiates eIF2B, restoring its exchange activity even in the presence of eIF2α-P. This overcomes the translational repression without touching the upstream kinases.

3

Restored Protein Synthesis & ISR Output

With eIF2B active, global translation resumes and the ATF4/CHOP stress transcriptional program is dampened. This underlies ISRIB's effects on protein folding, neuronal survival, memory and recovery from stress.

⚖️ Trans-ISRIB vs Other ISR / Translation Tools

  • Trans-ISRIB (this product)Potentiates eIF2B; reverses eIF2α-P repression (downstream)
  • Salubrinal / GuilintideInhibit eIF2α dephosphorylation (upstream, opposite)
  • PERK / GCN2 inhibitorsBlock upstream ISR kinases
  • Shared PathwayIntegrated stress response / translation initiation
  • Key DistinctionActs at eIF2B, not at kinases or eIF2α-P
  • OutputRestored protein synthesis; ↓ ATF4/CHOP

♻️ Downstream Biological Consequences

  • FactoreIF2B potentiated (GEF activity ↑)
  • InitiationeIF2-GTP recycling restored
  • TranslationGlobal protein synthesis resumes
  • TranscriptionATF4 / CHOP ISR program ↓
  • CellImproved folding & stress survival
  • NeuronPlasticity / memory rescue

Research Applications & Models

A precise tool for dissecting the integrated stress response and restoring translation in disease models.

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Neurodegeneration & Memory

The flagship use: Trans-ISRIB reverses ISR-driven repression to rescue protein synthesis and memory in neurodegeneration and brain-injury models.

ISR / eIF2B
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Protein-Folding & Proteostasis

Used to study ER stress, proteostasis and recovery of translation after stress.

Proteostasis
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Translation-Initiation Research

A fiducial eIF2B potentiator for initiation, ribosome-profiling and ISR assays.

Translation
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Cognitive & Synaptic Plasticity

Investigated for long-term potentiation and learning deficits linked to chronic ISR.

Plasticity
⚖️

ISR / Stress-Response Panel

Benchmarked against Salubrinal/kinase inhibitors to separate upstream from downstream ISR modulation.

ISR panel
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Traumatic Brain / Ischemia Models

Studied for restoring protein synthesis after injury or hypoxia.

Injury / Ischemia

Key Literature & Landmark Publications

The discovery and biology of ISRIB (trans-ISRIB) as an eIF2B-targeted ISR inhibitor.

Sidrauski C, et al. Pharmacological dimerization of eIF2B by ISRIB reverses the integrated stress response. Nature. 2015;524(7563):479-83.
doi: 10.1038/nature14814
Sidrauski C, et al. ISRIB blocks integrated stress response and enhances cognitive function. Proc Natl Acad Sci USA. 2013;110(49):16973-8.
doi: 10.1073/pnas.1315882110
Tsai HH, et al. ISRIB improves cognition after TBI by restoring translation. Nat Commun. 2020;11(1):5180.
doi: 10.1038/s41467-020-18866-7
Wong YL, et al. eIF2B structures reveal mechanism of ISRIB action. eLife. 2018;7:e32733.
doi: 10.7554/eLife.32733
Rabouw H, et al. ISRIB inhibits enterovirus and enhances translation recovery. PLoS Pathog. 2019;15(4):e1007700.
doi: 10.1371/journal.ppat.1007700

Available Sizes & Ordering

Research-grade Trans-ISRIB (CAS 1597403-47-8) with full QC documentation; standard packs and bulk custom quantities supported.

TierPack SizeStock StatusSuitable ForLead Time
Standard1gIn StockISR & translation assaysCold chain
Medium5gIn StockNeurodegeneration & memory modelsCold chain
Large10gIn StockLong-term in vivo & formulation studiesCold chain
Bulk100gIn StockFormulation & process developmentQuote to confirm
Industrial1KGMade to orderPilot/production scale, CMO supplyBatch delivery

💡 Reference sizes shown above; for exact pricing and availability please contact us for a quote. Bulk orders qualify for tiered discounts.

Frequently Asked Questions (FAQ)

What is Trans-ISRIB and what does it do?
Trans-ISRIB (ISRIB, trans isomer; CAS 1597403-47-8) is a potent integrated stress response (ISR) inhibitor. It does not block a kinase; instead it allosterically activates eIF2B — the GEF for translation-initiation factor eIF2 — thereby overriding the translational repression caused by phosphorylated eIF2α and restoring protein synthesis. Formula C18H18N2O2, MW 294.35.
How is Trans-ISRIB different from Salubrinal or PERK inhibitors?
Salubrinal and PERK/GCN2 inhibitors act upstream of eIF2α phosphorylation (and Salubrinal actually prolongs the ISR). Trans-ISRIB acts downstream at eIF2B, directly reversing eIF2α-P-mediated repression — a mechanistically distinct, translation-restoring approach.
What is the mechanism in neurodegeneration / cognition research?
Chronic ISR (eIF2α-P) represses translation and drives cognitive deficits. Trans-ISRIB potentiates eIF2B to resume protein synthesis and lower the ATF4/CHOP stress program, rescuing memory and neuronal survival.
What are the key experimental readouts?
Readouts include restored global translation / puromycin incorporation, eIF2B exchange activity, ATF4/CHOP mRNA & protein, polysome profiles, and cognitive/behavior endpoints in stress or injury models.
How soluble is Trans-ISRIB and how prepared?
Trans-ISRIB is soluble in DMSO (~10-30 mg/mL) and limited ethanol; aqueous solubility is very low (<0.1 mg/mL). Prepare DMSO stock and dilute into medium (final DMSO ≤0.1% v/v) for cell work; for in vivo use validated vehicles. Store the solid at -20 °C, sealed and protected from light; aliquot stocks to avoid freeze-thaw.
Is QC documentation provided?
Every batch ships with a Certificate of Analysis (COA) including HPLC purity, structural confirmation and MS data. MSDS/SDS and Certificates of Origin are available on request. Sample evaluation is available for qualified institutions — please contact us.

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Research-grade Trans-ISRIB (CAS 1597403-47-8) — purity ≥98% HPLC, COA included
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