Cortagen
Also known as: Ala-Glu-Asp-Pro · AEDP · Cortagen (Cytogen series) · synthetic brain-cortex tetrapeptide · AEDP tetrapeptide
Research focus
Brain cortex / peripheral nervous tissue (proposed neurotrophic and nerve-regeneration support)
US regulatory status
Not FDA-approved · Not compoundable
Evidence rating
No Human Data
Origin
Cortagen is a synthetic tetrapeptide (Ala-Glu-Asp-Pro) developed by the group of Vladimir Khavinson at the St. Petersburg Institute of Bioregulation and Gerontology (North-Western Branch, Russian Academy of Medical Sciences), with much of the experimental work carried out alongside the Pavlov Institute of Physiology and the Institute of Experimental Medicine. It belongs to the institute's "Cytogen" series of short synthetic peptides, which were designed by the institute's stated method of "directed synthesis": researchers chemically analyzed the amino-acid composition of a natural polypeptide extract from animal brain cortex (the preparation Cortexin) and then synthesized a short peptide intended to reproduce the active fragment. Per the Khavinson group's own publications, Cortagen is positioned as the brain-cortex member of this family — paralleling Epitalon (pineal), Vilon (thymus), and Livagen (liver). This places Cortagen firmly within the same single-institution research program and "peptide bioregulator" framework as the other Cytogens and Cytomax preparations, and essentially all of the primary Cortagen literature traces back to that group.
Plain-language summary
Cortagen is a lab-made four-amino-acid peptide (Ala-Glu-Asp-Pro) created by a single Russian gerontology institute as the "brain cortex" entry in its family of short peptides. It is marketed online for brain, nerve, and cognitive "support." The reality is that the published science is thin and almost entirely from that one group: a handful of rodent and test-tube studies (nerve-regeneration experiments in rats, gene-expression assays in mouse tissue and isolated immune cells) plus one lab study on blood cells taken from elderly people. There are no published clinical trials in people testing whether Cortagen improves memory, thinking, or any neurological condition, and no large independent randomized trials of any kind. What you can say is that early-stage, single-group laboratory work exists; what you cannot say is that any human benefit has been shown.
Claimed mechanism (as reported)
The Khavinson group proposes that short peptides such as Cortagen act as "bioregulators" that enter cells, reach the nucleus, and influence gene expression in a tissue-specific way — in this case favoring brain-cortex and nerve tissue. In published in-vitro and rodent work the peptide is reported to modulate transcription (for example, altering IL-2 gene activity in immune cells and changing expression of numerous transcripts in mouse heart on microarray) and, in the group's organotypic-culture model, to preferentially stimulate the outgrowth of brain-cortex explants. The broader mechanistic claim that these tetrapeptides bind DNA/histones and steer gene expression comes primarily from in-silico and in-vitro work by the same group and is not established through independent biochemical or human pharmacological studies. Mechanism for Cortagen specifically should be read as proposed and largely inferred from related peptides, not demonstrated in humans.
Evidence summary
The Cortagen-specific literature indexed in PubMed is small — on the order of a dozen-to-fifteen records, the great majority authored by Khavinson and colleagues at the St. Petersburg Institute of Bioregulation and Gerontology and collaborating Russian institutes. The evidence base is preclinical and mechanistic: rat sciatic-nerve regeneration experiments, organotypic tissue-culture "tissue-specificity" studies, and gene-expression assays in mouse heart and in isolated mouse immune cells. The only work touching human material is an ex-vivo study of chromatin in lymphocytes drawn from elderly subjects — a laboratory observation on cells, not a clinical efficacy trial. As of 2026 there are no published, peer-reviewed randomized controlled trials of Cortagen in humans, no independently replicated clinical outcomes, and no cognitive or neurological efficacy endpoints reported in people. Accordingly this profile is graded "No Human Data." Some secondary/marketing sources assert a human nerve-recovery effect, but a corresponding controlled human trial is not identifiable in the indexed literature; such claims should be treated as unverified.
What the research reports
Effect of tetrapeptide cortagen on regeneration of sciatic nerve
Grade DTurchaninova LN, Kolosova LI, Malinin VV, Moiseeva AB, Nozdrachev AD, Khavinson VKh · Bulletin of Experimental Biology and Medicine · 2000
Reported finding: After surgical transection and suturing of the sciatic nerve, intramuscular Cortagen (reported at 10 ug/kg for 10 days) was described as increasing regenerating-fiber growth rate and conduction velocity versus controls. Reported by the originating group only and not independently replicated.
Sample: Small rat cohorts (animal counts not standardized in abstract)
Methodology: D — single rodent study, single research group, animal model only, no human relevance demonstrated
Limitations: Rat-only model; small samples; single group; surgical-injury paradigm does not translate to human efficacy; no blinding or independent replication described.
Elucidation of the effect of brain cortex tetrapeptide Cortagen on gene expression in mouse heart by microarray
Grade CAnisimov SV, Khavinson VKh, Anisimov VN · Neuroendocrinology Letters · 2004
Reported finding: A short course of Cortagen was reported to alter expression of roughly 110 identifiable genes in mouse heart on cDNA microarray, with overlapping and distinct signatures versus Vilon, Epitalon, and melatonin. Presented as hypothesis-generating evidence of a transcriptional 'bioregulator' effect.
Sample: Female CBA mice, 5-day dosing course (per-group n not detailed in abstract)
Methodology: C — mechanistic preclinical (mouse) microarray, single research group, exploratory transcriptomics
Limitations: Exploratory microarray in mice; no functional/clinical outcome; single group; findings describe gene-expression changes, not therapeutic benefit; not independently confirmed.
Effects of short peptides on lymphocyte chromatin in senile subjects (Vilon, Epithalon, Livagen, Prostamax, Cortagen)
Grade CKhavinson VKh, Lezhava TA, Malinin VV · Bulletin of Experimental Biology and Medicine · 2004
Reported finding: In cultured leukocytes from elderly donors, Cortagen and other short peptides were reported to activate ribosomal genes and decondense (de-heterochromatinize) age-condensed chromatin. This is an in-vitro observation on human cells, not a measure of any clinical or cognitive outcome.
Sample: Leukocytes from subjects aged 75–88 (small donor pool typical of this group's work)
Methodology: C — ex-vivo human-cell laboratory study, single group, not a clinical efficacy trial
Limitations: Ex-vivo cell assay only; no clinical endpoint; small donor pool; single group; no blinding or independent replication; cannot support claims of in-vivo human benefit.
Tissue-specific effects of peptides / Peptides and Ageing (originating-group reviews and organotypic-culture reports)
Grade CKhavinson VKh, Malinin VV, Chalisova NI et al. · Bulletin of Experimental Biology and Medicine; Neuroendocrinology Letters; Advances in Gerontology (Uspekhi Gerontologii) · 2001–2004
Reported finding: These sources describe the directed-synthesis origin of Cortagen from the cortex extract Cortexin and report that, in organotypic culture, Cortagen preferentially stimulates outgrowth of brain-cortex explants — the basis for the 'tissue-specific bioregulator' framing. They confirm the Ala-Glu-Asp-Pro sequence and the brain-cortex positioning.
Sample: Rat-tissue explant cultures; review syntheses (no human trial cohorts)
Methodology: C/D — narrative reviews and organotypic tissue-culture studies, single research group
Limitations: Reviews and in-vitro culture work from the originating group; no controlled human data; tissue-culture 'specificity' does not establish clinical effect; inherent single-source bias.
Administration reported in studies
In the underlying animal experiments, Cortagen was typically given by intramuscular injection over short consecutive-day courses (for example, the rat sciatic-nerve work reported roughly 10 ug/kg/day for about 10 days); in-vitro studies simply added the peptide to cultured cells at various concentrations. No validated human dosing exists because no human clinical trials have been published. Vendor and consumer protocols circulating online (subcutaneous or intranasal "courses") are not derived from controlled human studies and are not supported by the indexed literature. This is a summary of research conditions — not a dosing recommendation and not a protocol endorsed by TPC.
This section reports what published studies describe. It is not a dosing recommendation from TPS.
Safety record
There is no meaningful human safety dataset for Cortagen. No published clinical trials means no systematically collected adverse-event data, no pharmacokinetics, and no information on long-term use, drug interactions, immunogenicity, or effects of repeated dosing in people. The originating group's animal and in-vitro reports did not surface as raising specific toxicity flags, but absence of reported harm in a few small single-group preclinical studies is not evidence of safety. Because material sold online as Cortagen is unregulated "research chemical" of unverified identity and purity, sterility and contamination are additional real-world concerns. No claim of safety can be made.
US legal status
Not FDA-approved for any use. Not on the FDA 503A compoundable bulk drug substances list and not legally compoundable for human clinical use in the United States. Cortagen is sold online only as a "research chemical" / "not for human consumption" product; vendors in that channel are unregulated and are not verified by TPC. Nothing here should be read as endorsing personal use.
Open research questions
- ? Has any independent laboratory — outside the St. Petersburg Institute of Bioregulation and Gerontology and its immediate collaborators — replicated the reported nerve-regeneration or gene-expression effects of Cortagen?
- ? Does any randomized, blinded, placebo-controlled human trial of Cortagen exist for any neurological or cognitive endpoint, with prespecified outcomes and adequate sample size?
- ? What are the basic human pharmacokinetics — absorption, bioavailability by the routes vendors promote, distribution to the central nervous system, and half-life — none of which appear to be published?
- ? What is the long-term human safety profile, including immunogenicity, effects of repeated courses, and contamination/identity risk from unregulated 'research chemical' sourcing?
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