Cortagen

Ala-Glu-Asp-Pro, AEDP, Кортаген; sometimes grouped with Cortexin (the bovine cortex polypeptide extract it was modelled on) and with Pinealon (a related tripeptide)

Immune & bioregulators

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Summary

Class: Synthetic tetrapeptide (four amino acids) from the Khavinson "peptide bioregulator" family, designed from the amino-acid composition of a cortex-derived polypeptide extract
Mechanism: Proposed to enter cells and bind DNA/histones to shift gene expression toward neuronal survival and repair, and to support regeneration of injured nerves — shown only in rodents and cell culture by one group
Routes studied: Intramuscular and intraperitoneal injection (rodents); community: oral capsules, sublingual, occasionally subcutaneous
Dose range reported: Rodent studies: roughly 0.5–10 µg/kg per injection in courses. No human trials. Community-reported: 1–10 mg/day for 10–20 days, repeated two or three times a year, following the general Khavinson "course" pattern
Half-life: Not characterised. Short peptides of this type are expected to be cleared from blood within minutes; the originating group argues the active principle is intracellular
Storage: Lyophilised: refrigerate, protect from light. Capsules: room temperature, dry. Reconstituted: refrigerate, use within ~4 weeks (community practice)
Regulatory status: Not approved as a medicine anywhere. Marketed in Russia as a dietary supplement / "parapharmaceutical" †

Doses are as reported in studies or by the community — never recommendations.

1What it is

Cortagen is one of a family of very short synthetic peptides developed by Vladimir Khavinson and colleagues at the St Petersburg Institute of Bioregulation and Gerontology. The group's method was to take an organ extract — here Cortexin, a polypeptide preparation from calf cortex used as a medicine in Russia — analyse its amino-acid composition, and synthesise a short peptide that, they argue, captures its tissue-specific regulatory action. Cortagen (Ala-Glu-Asp-Pro) is the "brain cortex" tetrapeptide in that scheme; Vesilute (#98), Vesugen, Epitalon, Pinealon and others follow the same logic for other tissues.

It is important to be plain about the evidence base. Nearly everything published on Cortagen comes from the originating group and its collaborators, mostly in Russian or in Bulletin of Experimental Biology and Medicine translations, and consists of rodent and cell-culture experiments. There are no controlled human trials. Independent replication is, as far as we know, absent. This does not make the findings wrong, but it means the grades below are the ceiling, not the floor, of uncertainty.

2How it's thought to work

The originating group's model, applied to all its short peptides:

Nuclear entry and gene regulation. Very short, charged peptides are proposed to cross cell and nuclear membranes and bind to specific DNA sequences or histone proteins, altering transcription of genes involved in cell survival, differentiation and proliferation (Khavinson 2011, 2013). Molecular-modelling and binding studies support plausibility; direct proof in living brain tissue is lacking.

Nerve regeneration. In rats with a crushed or transected sciatic nerve, Cortagen is reported to accelerate recovery of nerve conduction and limb function, attributed to effects on Schwann cells and axonal growth.

Neuroprotection. Reported to improve survival of cortical neurons in culture under oxidative or ischaemic stress and to normalise brain electrical activity in rodent injury models.

"Geroprotection". The group reports improved cortical cell function in old animals and in aged cell cultures, in line with their broader claim that short peptides restore age-related declines in protein synthesis.

Proposed: a tetrapeptide directed at brain cortex, reported to support nerve regeneration in animal models. No controlled human data.Schematic — not to scale

3What the research shows

Peripheral nerve regeneration

Rat sciatic-nerve injury models are the best-known Cortagen experiments: faster recovery of conduction velocity and function compared with saline controls after a course of injections (Khavinson and colleagues, early 2000s, Bull Exp Biol Med). Single group; modest sample sizes.

Graded C/D

Cortical neuron survival and function

Rodent and organotypic culture studies report increased neuron survival, reduced apoptosis markers and shifts in gene expression after Cortagen exposure. Sometimes compared with Cortexin or Pinealon, with the short peptide reported as comparable or superior.

Cognition and ageing in rodents

Scattered reports of improved learning in old or lesioned rats; small, descriptive, not replicated independently.

Human cognitive or neurological outcomes

No controlled human studies. Russian review articles on "peptide bioregulators in neurology" (e.g. Umnov 2013) summarise clinical experience that is largely with Cortexin, the extract, rather than Cortagen itself. The two are often conflated online; they are different products with different evidence. [4]

4Reported side effects and interactions

Literature-reported

No adverse effects reported in the rodent work. No human safety data.

Community-reported

Almost always described as "unremarkable": occasional mild headache, vivid dreams or transient fatigue in the first days of a course. Oral capsule users rarely report anything at all, which may reflect low systemic absorption as much as safety.

Theoretical. a peptide proposed to alter gene transcription and support cell proliferation in the nervous system carries a theoretical caution for anyone with a history of CNS tumours; no data either way. Oral peptides of this size are usually digested, so what, if anything, reaches tissue from a capsule is unknown.

Interactions. none established.

Markers researchers commonly monitor

No compound-specific markers exist. If it is in a protocol:

Marker	Why it's watched
CBC and CMP	general baseline; there is no human safety literature.
A repeatable cognitive test and, where relevant, a nerve-function measure (e.g. a clinician's nerve conduction study for a known neuropathy)	the only way to tell whether anything is happening, given the rodent claims are about nerve regeneration and cognition.
Sleep log	vivid dreams and fatigue are community-reported.
hs-CRP	general inflammation marker; the originating group frames many effects as anti-inflammatory.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Sold mostly as oral capsules (typically 10–20 mg per capsule, labelled as a supplement) and, less commonly, as powder for injection in vials of a few milligrams. For injectable forms, with and refrigerate. Doses in the community are in milligrams, far above the microgram-per-kilogram range used in rodents, which is a disconnect worth noticing.

Open in calculator, pre-loaded →

6Commonly studied alongside

Other Khavinson peptides — Epitalon and Pinealon (brain/pineal), Vesilute (#98), Vesugen, Cardiogen, Livagen, Thymogen — usually as sequential "courses". Cortexin and Cerebrolysin as the organ-extract comparators. Semax (#36) and Selank (#37) in Russian neuro-pharmacology generally. No combination has controlled data.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Not FDA-approved; not a lawful dietary ingredient; not on the Category 2 compounding list to our knowledge †
European Union	Not authorised as a medicine or food supplement ingredient
United Kingdom	Not licensed
Australia	Not approved
South Africa	Not registered
Russia	Sold as a dietary supplement / parapharmaceutical, not a registered medicine †; Cortexin (the extract) is a registered medicine
Sport (WADA)	Not specifically listed; non-approved substances fall under S0 †

8Open questions

Does Cortagen reach the brain or peripheral nerves at all after oral or dosing in humans? No pharmacokinetic data.
Independent replication of the sciatic-nerve and neuron-survival findings outside the originating group.
Any human outcome data — currently none.
Whether the gene-regulation model (peptide-DNA binding) operates in living tissue or only .

9References

1Khavinson VKh et al. (2011). Short cell-penetrating peptides: a model of interactions with gene promoter sites. Bull Exp Biol Med. PubMed
2Khavinson VKh, Malinin VV (2005). Gerontological Aspects of Genome Peptide Regulation. Karger (monograph summarising the group's short-peptide work, including Cortagen). PubMed
3Khavinson VKh et al. (2000s). Peptide stimulation of sciatic nerve regeneration in rats (Cortagen). Bull Exp Biol Med [identify exact paper]. PubMed
4Umnov RS, Linkova NS, Khavinson VKh (2013). Neuroprotective effects of peptide bioregulators in people of various age: review of the literature. Adv Gerontol. PubMed
5Khavinson V et al. (2021). Peptide regulation of gene expression: a systematic review. Molecules [verify]. PubMed · DOI

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

Not enough data yet. 0 of the 50 members needed have logged this compound for 4+ weeks. We don't show anything below 50, so no one can be identified.

11Page history

26 Oct 2026Profile published — awaiting medical review

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