ISRIB Overview
ISRIB (Integrated Stress Response Inhibitor) is a synthetic small-molecule compound studied for its ability to modulate cellular stress signaling by counteracting activation of the integrated stress response (ISR). It is widely used in laboratory research focused on translational regulation, protein synthesis, and cellular resilience under stress conditions.
ISRIB is not approved for human or veterinary use and is supplied strictly for laboratory and analytical research purposes.
Mechanism of Action
ISRIB functions by enhancing the activity of eukaryotic initiation factor 2B (eIF2B), the guanine nucleotide exchange factor essential for translation initiation. During cellular stress, phosphorylation of eIF2α suppresses eIF2B activity and reduces global protein synthesis.
In research models, ISRIB restores translational activity despite eIF2α phosphorylation by stabilizing eIF2B in an active conformation. This makes ISRIB a critical research tool for studying:
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Integrated stress response (ISR) signaling
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Translational control and protein synthesis
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Cellular adaptation to metabolic and proteotoxic stress
Chemical Structure
Chemical Name:
ISRIB
Synonyms:
Integrated Stress Response Inhibitor
Molecular Formula:
C₂₂H₂₄Cl₂N₂O₄
Molecular Weight:
451.34 g/mol
CAS Number:
1597403-47-8
Structural Description:
ISRIB is a fluorinated small molecule with a rigid aromatic scaffold that enables high-affinity interaction with eIF2B. Its symmetrical structure stabilizes the active form of eIF2B, allowing continued translation initiation under stress conditions. Structural identification and molecular data are available via PubChem.
Physical and Chemical Properties
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Appearance: White to off-white crystalline solid
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Solubility: Poor aqueous solubility; soluble in DMSO and common organic solvents
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Stability: Stable under dry, cool, and light-protected storage conditions
Research Focus Areas
ISRIB is commonly examined in laboratory research related to:
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Integrated stress response signaling
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Translational regulation and protein synthesis
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Proteostasis and cellular stress models
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Neurobiology and cognitive research pathways
Research Use Disclaimer
ISRIB is intended for research use only.
Not for human consumption, therapeutic use, or diagnostic application. All handling and use must comply with applicable laws, regulations, and laboratory safety standards.
Summary
ISRIB is a small-molecule integrated stress response inhibitor with a defined chemical structure and a well-characterized mechanism involving eIF2B activation. Its ability to restore protein synthesis during stress makes it a foundational research tool in studies of translational control, cellular resilience, and stress-response biology.
| CAS Number | 1597403-47-8 |
| Other Names | ISRIB, trans-ISRIB, ISRIB (trans-isomer), cis-ISRIB |
| IUPAC Name | Trans-N,N′-(Cyclohexane-1,4-diyl)bis(2-(4-chlorophenoxy)acetamide) |
| Molecular Formula | C₂₂H₂₄Cl₂N₂O₄ |
| Molecular Weight | 451.34 g/mol |
| Dry-Fill Capsule Concentration | 25mg |
