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; not approved as a medicine in Western jurisdictions.
- Independent Western replication of the distinctive Khavinson-school mechanistic claims — particularly the direct DNA-binding transcriptional mechanism — remains limited.
- Remains a research chemical in all jurisdictions including the UK.
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 |
|---|---|---|---|
| Intranasal / parenteral (research) | Microgram-range doses in animal and clinical-research protocols following the Khavinson clinical convention | Cyclical, typically 10–20 day courses at once-daily dosing following the standard Khavinson short-peptide bioregulator pattern | Short courses repeated periodically (every 4–6 months) rather than continuous administration; multi-year cyclical use in gerontoprotective protocols |
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 standard 10-day-course-per-6-months protocol 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
- · Not licensed for human use in the UK, EU, or US — supply for human consumption is prohibited under the Human Medicines Regulations 2012.
- · 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
Not a licensed medicine in the UK. Research chemical only.
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 10-day 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: research peptides are sold strictly for in vitro and preclinical laboratory purposes. Importation or supply for human consumption is not permitted under UK medicines legislation.