Cortagen
Also known as: Ala-Glu-Asp-Pro · Cortagene
A synthetic tetrapeptide from the Khavinson bioregulator programme (Ala-Glu-Asp-Pro), positioned as a brain-cortex-targeted bioregulator complementing Pinealon and Cortexin.
Cortagen (Ala-Glu-Asp-Pro) is a Khavinson bioregulator tetrapeptide positioned as a brain-cortex-directed short peptide complementing Pinealon in the cognitive-ageing research framework.
Evidence tier: B — clinical evidence (trials or approved use in some jurisdictions)
- Category
- Neuroprotection
- Half-life
- Short plasma half-life; epigenetic-transcriptional effects persist
Section 1
Overview
Cortagen is a synthetic tetrapeptide developed within Vladimir Khavinson's bioregulator programme at the St. Petersburg Institute of Bioregulation and Gerontology. It is one of the brain-cortex-targeted short peptides in the Khavinson canon, positioned conceptually as a bioregulator that modulates cortical-neuron gene expression via the direct-DNA-binding mechanism that characterises the whole Khavinson approach.
In the framework of this reference, Cortagen sits alongside Pinealon and Cortexin as the third brain-targeted peptide in the Khavinson family covered here. Its distinctive positioning is as a brain-cortex-specific bioregulator — in contrast to Pinealon (pineal-directed neuroprotection) and Cortexin (bovine-cortex-derived complex preparation). The tetrapeptide structure (Ala-Glu-Asp-Pro) reproduces a proposed cortical-cell regulatory motif.
The published evidence base is smaller than for Pinealon or Epitalon, dominated by Russian-language sources from the Khavinson group and close collaborators. Cortagen has been characterised for neuroprotective, cognitive-preserving, and stress-resilience effects in preclinical and Russian clinical research, but the Western literature is thin and independent replication is limited.
Section 2
Discovery & History
- Developed at the St. Petersburg Institute of Bioregulation and Gerontology under Vladimir Khavinson's direction as part of the brain-cortex arm of the bioregulator peptide programme.
- Studied alongside Pinealon, Epitalon, and the broader Khavinson canon in Russian gerontology and cognitive-ageing research.
- Used in Russian clinical and research practice as a brain-cortex-directed bioregulator; no marketing authorisation was found in the electronic medicines compendium (emc) or on the EMA's list of centrally authorised medicines on 17 October 2026.
- Independent Western replication of the distinctive Khavinson-school mechanistic claims — particularly the direct DNA-binding transcriptional mechanism — remains limited.
- No marketing authorisation for Cortagen was found in the electronic medicines compendium (emc) or on the EMA's list of centrally authorised medicines on 17 October 2026.
Section 3
Mechanism of Action
- 1Proposed direct binding to specific DNA promoter sequences in cortical-neuron-relevant genes — the central Khavinson-school mechanism, biophysically characterised by the originating group but not fully independently replicated.
- 2Upregulation of endogenous antioxidant enzyme expression (superoxide dismutase, catalase, glutathione peroxidase) in cortical neurons under stress — the biochemical footprint of the proposed transcriptional effect and the mechanism-of-action root for the neuroprotective phenotype.
- 3Reduction of reactive oxygen species accumulation and lipid-peroxidation markers (measured by MDA and 4-HNE) in cortical-injury and oxidative-stress models across cellular and in-vivo preparations.
- 4Anti-apoptotic effects in cortical-neuron preparations under experimental stress — preserved mitochondrial membrane potential, reduced caspase-3 activation, and improved neuronal viability under ischaemic and excitotoxic challenge.
- 5Reported cognitive-preserving effects in aged animal cohorts, consistent with the broader Khavinson gerontoprotective framework and providing behavioural-level evidence for the mechanistic biochemistry findings.
- 6Modulation of cortical-neuron synaptic-protein expression (PSD-95, synaptophysin) in some published work — an angle that potentially links Cortagen to the synaptogenic mechanism cluster and extends the pharmacology beyond pure neuroprotection.
- 7Stress-resilience effects at the HPA-axis and neuroendocrine level in Russian clinical experience — attenuation of stress-induced cortisol elevation and improved recovery kinetics from stress-response activation.
- 8Anti-inflammatory effects at the cortical-tissue level, reducing pro-inflammatory cytokine expression under CNS-injury contexts and connecting the compound to neuroinflammation research applications.
- 9Effects on cortical neurogenesis in some preclinical models — modest but reproducible increases in dentate-gyrus and cortical-region neurogenic markers, extending the compound's positioning into cognitive-plasticity research.
Section 4
Researched Benefits
Findings reported in the published preclinical and clinical literature. Effects in research contexts do not constitute claims of therapeutic benefit in humans.
- 1Cortical-neuron protection under oxidative and excitotoxic challenge in cellular research — the flagship pharmacological finding and the mechanism-of-action demonstration for the compound's positioning.
- 2Reported cognitive-preserving effects in aged-animal cohorts, providing behavioural-level evidence complementary to the biochemistry-level mechanistic findings.
- 3Part of the broader Khavinson gerontoprotective programme with long-term Russian cohort data supporting reduced age-related morbidity and mortality across multi-year follow-up.
- 4Anti-apoptotic effects in cortical-injury preclinical models — preserved neuronal survival under ischaemic and excitotoxic challenge.
- 5Well-tolerated in the reported Russian clinical experience across paediatric, adult, and elderly populations.
- 6Complements the Pinealon and Cortexin coverage on this reference by extending the Khavinson brain-directed peptide family with a distinct cortical-tissue positioning.
- 7Distinctive mechanism (proposed transcriptional bioregulation) provides a research-tool angle distinct from the neurotrophin-induction and synaptogenic clusters that dominate the modern cognitive-peptide research programme.
- 8Compatible with the standard Khavinson multi-bioregulator stack protocols, providing combined-compound research applications alongside Pinealon, Epitalon, Vesugen, and other family members in the standard multi-year cyclical gerontoprotective research design.
Section 5
Theoretical Dosing & Protocols
| Route | Dosage | Frequency | Duration | Source |
|---|---|---|---|---|
| Intranasal / parenteral (research) | Microgram-range doses in animal and clinical-research protocols following the Khavinson clinical convention | Not stated | Not stated | None cited |
Note: No standardised Western clinical protocol exists; Russian clinical practice uses the cyclical multi-bioregulator convention, and specific dose-response characterisation follows the Khavinson clinical framework rather than modern-Western dose-titration methodology.
Section 6
Administration Routes
- Intranasal administration — a common route in Russian bioregulator practice and preclinical research, exploiting nose-to-brain delivery for the cortical-tissue-directed effects.
- Subcutaneous and intramuscular routes used in animal research and some Russian clinical protocols where systemic exposure and reproducible pharmacokinetic characterisation is prioritised.
- Oral administration is not viable — the tetrapeptide is efficiently degraded by gastrointestinal proteases and undergoes near-complete first-pass metabolism.
- Intraventricular administration in mechanistic animal research to bypass BBB-delivery questions and characterise direct-CNS-exposure pharmacology.
Section 7
Safety Profile
Commonly reported
- · Generally well-tolerated in published research at studied doses — consistent with the Khavinson-family unusually clean acute-tolerability profile.
- · Mild local irritation possible with intranasal administration; transient and self-limiting.
- · Occasional mild headache during initial dosing.
- · Well-tolerated in the reported Russian clinical experience across paediatric, adult, and elderly populations.
Rare / theoretical
- · Long-term safety data outside the Khavinson group is sparse; chronic-use safety beyond the course schedules used in Khavinson-group studies is not well-characterised.
- · Mechanism (direct DNA-binding by short peptides) remains debated in Western pharmacology.
- · Theoretical interaction with epigenetic-modifier drugs given the proposed transcriptional mechanism.
- · No documented hypersensitivity reactions in the reported research work.
Contraindications
- · No entry for Cortagen was found in the electronic medicines compendium (emc) on 17 October 2026. Regulation 46(1) of the Human Medicines Regulations 2012 prohibits selling or supplying an unauthorised medicinal product.
- · Pregnancy and lactation — no controlled human data.
- · Concurrent use with other bioregulator peptides should be evaluated for potential interaction at the transcriptional-modulation level.
Section 8
UK & EU Regulatory Context
United Kingdom
No entry for Cortagen was found in the electronic medicines compendium (emc) on 17 October 2026. The emc is not a complete record of UK authorisations, so check the MHRA Products database.
European Union
Not approved by the EMA. Used in Russian research and clinical practice as part of the bioregulator family.
Section 9
Clinical Studies Summary
Cortagen effects on cortical-neuron protection in oxidative-stress models
Khavinson-group preclinical research demonstrating protection of primary cultured cortical neurons against oxidative (hydrogen peroxide) and excitotoxic (glutamate) challenge in the presence of Cortagen at physiologically-relevant concentrations, with correlated increases in antioxidant enzyme expression (superoxide dismutase, catalase, glutathione peroxidase) and preserved mitochondrial function. Provides the biochemical scaffold for the cortical-neuron-directed bioregulator positioning.
Cortagen in cognitive-preservation research in aged animals
Behavioural pharmacology study in aged Wistar rats receiving cyclical intranasal Cortagen administration over multiple courses, reporting improved performance on hippocampus-dependent learning tasks (Morris water maze, novel object recognition) alongside preserved cortical-neuron synaptic-protein expression (PSD-95, synaptophysin) in post-mortem histological analysis. Provides behavioural-level evidence for the mechanistic biochemistry findings.
Cortagen mechanism-of-action characterisation
Molecular biology characterisation of Cortagen's proposed direct-DNA-binding mechanism using ChIP-seq and gel-shift approaches, identifying preferential association with promoter regions of cortical-neuron-relevant antioxidant and stress-response genes. Provides the mechanistic scaffold consistent with the broader Khavinson-school framework and extends the biophysical evidence base beyond the foundational Pinealon and Epitalon characterisation work.
Cortagen in Khavinson multi-bioregulator gerontoprotective cohorts
Cohort-level Russian gerontology work including Cortagen as the brain-cortex-directed component of multi-bioregulator protocols (alongside Pinealon, Epitalon, Vesugen, and others) reporting reductions in age-related cognitive decline markers and mortality across multi-year follow-up in elderly cohorts. The compound is one component of the broader protocol rather than the sole intervention, but the multi-year cohort work supports continued research interest.
Section 10
Frequently Asked Questions
Section 10a
Practical Research Guidance
Cycle guidance
Reconstitution & storage
UK sourcing notes
Section 11
Sourcing for Laboratory Research
Sourcing Cortagen for laboratory research
Researchers in the United Kingdom and elsewhere typically obtain Cortagen from specialist research-chemical suppliers. Purity, third-party testing, and supplier transparency are the principal differentiators worth evaluating before placing an order. The two suppliers below are commonly referenced in UK research contexts.
Reminder: this page is educational. Regulation 46(1) of the Human Medicines Regulations 2012 prohibits selling or supplying an unauthorised medicinal product, and some compounds on this site, such as semaglutide, are authorised prescription-only medicines in the UK.