ISRIB
Integrated stress response (ISR) inhibitor, eIF2B activator, preclinical memory data only.
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Pharmacology
Contents
WHAT IS ISRIB?
Detailed overview
ISRIB (integrated stress response inhibitor) is a small molecule that binds the eIF2B guanine-nucleotide exchange factor and inhibits the integrated stress response (ISR). Acting as a molecular staple, it cross-bridges the two tetrameric halves of eIF2B to stabilize the fully active enzyme, restoring protein synthesis even when eIF2-alpha has been phosphorylated during stress. In rodent models it enhanced spatial and fear-associated learning and corrected cognitive deficits after traumatic brain injury and in Alzheimer's and aging-related paradigms. There are no human clinical trials: safety in humans is essentially unstudied and the compound has never been approved for human use, so it exists only as an experimental research chemical.
Mechanism
eIF2B activator / ISR inhibitor
Evidence
Preclinical only (no human data)
Legal status
Unapproved research chemical
Receptor profile
- eIF2B (guanine-nucleotide exchange factor)Strong
- eIF2-alpha phosphorylation block (ISR inhibition)Strong
- Age-related memory declineModerate
Safety
Side effects, stop signs, contraindications
Side effects · 5
- No human safety data: only preclinical (rodent and cell) studies exist; the compound has never been tested in humans
- The long-term consequences of sustained integrated stress response inhibition are unknown (the ISR serves an important protective and protein quality-control role)
- Theoretical risk that switching off the ISR weakens cellular defenses against misfolded proteins or promotes aberrant survival
- Poor water solubility, which historically complicated formulation and bioavailability
- Unknown long-term safety and incomplete toxicity profile in humans
Contraindications · 3
- Pregnancy and breastfeeding: safety not established, avoid
- Cancer or elevated cancer risk: ISR inhibition may theoretically affect cell stress and survival pathways
- Not an approved medicine; experimental research chemical, not recommended without clinical supervision
Related Nootropics
Same therapeutic category
Studies
Related research and clinical findings
Pharmacological brake-release of mRNA translation enhances cognitive memory
Sidrauski C, Acosta-Alvear D, Khoutorsky A, et al.
Stress responses. Mutations in a translation initiation factor identify the target of a memory-enhancing compound
Sekine Y, Zyryanova A, Crespillo-Casado A, et al.
Inhibition of the integrated stress response reverses cognitive deficits after traumatic brain injury
Chou A, Krukowski K, Jopson T, et al.
Binding of ISRIB reveals a regulatory site in the nucleotide exchange factor eIF2B
Zyryanova AF, Weis F, Faille A, et al.
Small molecule cognitive enhancer reverses age-related memory decline in mice
Krukowski K, Nolan A, Frias ES, et al.
Correction of eIF2-dependent defects in brain protein synthesis, synaptic plasticity, and memory in mouse models of Alzheimer's disease
Oliveira MM, Lourenco MV, Longo F, et al.
FAQ
FAQ
Integrated stress response (ISR) inhibitor, eIF2B activator, preclinical memory data only.
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Structure & chemistry
The information here is strictly for educational and scientific purposes. It does not replace medical advice or clinical consultation, and it does not encourage illegal substance or pharmaceutical use. Data is sourced. When in doubt, consult your doctor.