Cortagen

Overview

Cortagen is a synthetic tetrapeptide — Ala-Glu-Asp-Pro ("AEDP") — from Vladimir Khavinson's family of "short peptide bioregulators," developed at the St. Petersburg Institute of Bioregulation and Gerontology. It was produced by directed synthesis based on amino-acid analysis of cortexin, a cerebral-cortex polypeptide preparation, and is marketed as a brain/nervous-system "bioregulator" with claimed neurotrophic and geroprotective activity.

Its chemistry is well defined. PubChem (CID 18439621) confirms the structure: molecular formula C17H26N4O9, average molecular weight 430.4 g/mol, all-L (natural) stereochemistry.

The honest evidence picture, however, is limited, older, and almost entirely preclinical. The strongest peer-reviewed data are a single rat sciatic-nerve regeneration study (2000) and ex-vivo / in-vitro chromatin-decondensation and gene-reactivation observations in lymphocytes of elderly subjects. All located research originates from the Khavinson group or close collaborators, with no independent Western replication and no published human clinical trial. It is not approved by the FDA or EMA and is sold only as a research chemical.

Chemistry and structure

Values above are drawn from PubChem CID 18439621 (InChIKey PLTRIMAUDDQYRV-NAKRPEOUSA-N). No authoritative CAS number is listed in PubChem. Multiple chemical vendors (e.g. BOC Sciences) list CAS 335591-03-2, but this is not confirmed against a primary CAS registry entry — vendor CAS (and even vendor molecular-formula) claims should be treated with caution.

Mechanism of action

• DNA/promoter interaction and gene-expression modulation — as a short peptide, cortagen is proposed to enter cells and the nucleus and modulate gene expression by interacting with specific DNA/promoter regions (the Khavinson epigenetic-bioregulation model). [Hypothesis] (Developer-group model; not independently established)
• Chromatin decondensation / gene reactivation — induces decondensation of heterochromatin and reactivation of previously repressed (e.g. ribosomal) genes in lymphocytes/leukocytes of elderly subjects. [In vitro] (PMID 15085253 and related chromatin studies, Khavinson group)
• Peripheral nerve regeneration — enhances sciatic-nerve fiber regeneration and conduction velocity after injury in rats. [Animal] (Turchaninova et al., Bull Exp Biol Med 2000)
• Neurotrophic / neuroprotective and geroprotective effects — derived to mimic cortexin activity; framing from developer/vendor literature on a preclinical basis only. [Hypothesis] (Developer/vendor framing; preclinical basis only)

Research and evidence

Human evidence. No published human clinical trials (RCTs or otherwise) were located. The most "human-adjacent" data are ex-vivo / in-vitro studies on lymphocytes and leukocytes obtained from elderly subjects (age ~75–88) showing heterochromatin decondensation and reactivation of age-repressed genes — these are laboratory-cell observations [In vitro], not clinical efficacy or safety data. All located research originates from the Khavinson group or close collaborators. In short: no well-established human clinical trials. Human dosing, pharmacokinetics, bioavailability, and half-life are not established in primary sources (vendor "half-life" figures are unverified).

Status and regulation

Cortagen is not approved by the FDA or EMA for any indication. There is no evidence of Western marketing authorisation; it is sold only as a research-grade chemical / research reagent, not authorised for human use. Any human use would make it an unauthorised (unlicensed) medicine.

Note that the related preparation cortexin is used medically in Russia, but that is a different, polypeptide product — it should not be conflated with the cortagen tetrapeptide. Whether cortagen itself holds any Russian/EAEU marketing authorisation was not confirmed in accessible sources.

WADA status: no source was found asserting cortagen is on the WADA Prohibited List, so no class code is stated here. WADA sport-prohibition is a separate axis from legality.

Safety

• Human safety profile is not established in verifiable sources — no toxicology, pharmacokinetics, or adverse-event data of adequate quality were found.
• The biological effects reported are from animal and cell-culture models, which do not establish safety in humans.
• Material sold as a research reagent is not a quality-controlled medicine and may vary in identity, purity, and sterility.
• No human dosing has been established; any human use is experimental and unsupervised by design. Vendor dosing charts are not backed by clinical evidence.

Legal status

Cortagen's regulatory classification is a research reagent ("research use only") — it is not approved for human use in the US or EU. "No specific ban" is not affirmative permission: a compound becomes an unauthorised medicine the moment it is intended for human use, regardless of how it is labeled at point of sale. The Russian medical use of the separate cortexin preparation does not confer legality on the cortagen tetrapeptide. Regulatory status differs by country and can change. This is not legal advice — verify the status in your own jurisdiction. (Dated 2026-07-08.)

How it compares

• Epitalon — another Khavinson "short peptide bioregulator" and a synthetic tetrapeptide (Ala-Glu-Asp-Gly, AEDG), sharing Cortagen's pattern of bold geroprotective / epigenetic claims resting largely on the same research lineage with limited independent replication.
• Semax and Selank — Russian nootropic/neuropeptides that, like Cortagen, are studied largely within Russian research programs; they differ in origin and have somewhat broader (though still limited) literature.
• Cerebrolysin — a brain-derived peptide preparation studied for neurological indications; it is a mixture rather than a single defined peptide, but shares the neurotrophic framing applied to Cortagen.

Common misconceptions

• "Cortagen is a proven neuroregenerative drug." The nerve-regeneration data are a single rat study [Animal]; there is no published human clinical trial. It is not a proven human therapy.
• "Cortagen and cortexin are the same thing." Cortexin is a multi-component cerebral-cortex polypeptide preparation used medically in Russia; Cortagen is a single synthetic tetrapeptide (Ala-Glu-Asp-Pro) derived from it. They are different products.
• "Its CAS number is 335591-03-2." That is a vendor-listed number, unverified against a primary CAS registry; PubChem lists no CAS for this compound, so it should not be treated as authoritative.
• "It reactivates genes by binding DNA." DNA/promoter interaction and gene-expression modulation is a hypothesis-level claim from the developers' group [Hypothesis]; the chromatin-decondensation observations are in vitro [In vitro], not proof of a physiological mechanism in humans.
• "Not banned means legal to take." No specific ban is not affirmative permission; Cortagen is a research reagent and becomes an unauthorised medicine the moment it is intended for human use.

Russian research

Essentially all of the Cortagen (Ala-Glu-Asp-Pro) evidence base comes from a single Russian research lineage — V.Kh. Khavinson and the St. Petersburg Institute of Bioregulation and Gerontology and its collaborators — and it is surfaced here for completeness rather than as proof of efficacy. The work is older, preclinical, and published largely in the group's own venue (Bulletin of Experimental Biology and Medicine); no independent Western replication and no registered human clinical trial were located.

• [Animal] Peripheral-nerve regeneration (the most-cited result). Cortagen 10 µg/kg intramuscularly for 10 days after sciatic-nerve transection-and-suture in male Wistar rats increased the regenerating nerve-fiber growth rate by ~27% and conduction velocity by ~40%. This is a rat result — any human framing of "27–40%" is unsupported. Source: Turchaninova, Kolosova, Malinin, Moiseeva, Nozdrachev, Khavinson, "Effect of tetrapeptide cortagen on regeneration of sciatic nerve," Bull Exp Biol Med 2000 (PMID 11276314). A brief follow-up "delayed effect" communication reports continued nerve-function restoration (Kolosova et al., Dokl Biol Sci 2002, PMID 12134478 — no abstract; title/metadata only).

• [Animal · microarray] Cardiac gene expression. In female mice given Cortagen for 5 days, a heart-tissue microarray found significant change in 234 clones (~1.53%) mapping to 110 known genes (maximum up +5.42-fold, maximum down −2.86-fold), with effects described as partly shared with and partly distinct from Vilon, Epitalon and melatonin. Source: S.V. Anisimov, V.Kh. Khavinson, V.N. Anisimov, "Elucidation of the effect of brain cortex tetrapeptide Cortagen on gene expression in mouse heart," Neuro Endocrinol Lett 2004 (PMID 15159690). A gene-expression fingerprint is not a clinical outcome.

• [In vitro] Tissue-specific explant activity. In organotypic culture, Cortagen stimulated growth specifically of rat cerebral-cortex explants (tissue-specific among the "cytogen" peptides), consistent with the group's tissue-targeting framing. Source: Khavinson, "Tissue-specific effects of peptides," Bull Exp Biol Med 2001 (PMID 11713572).

• [Animal] Antioxidant / free-radical effects. Cortagen (together with epitalon) reduced lipid-peroxidation products and protein oxidative modification in serum and cerebral cortex in rats. Source: Kozina, "Effects of bioactive tetrapeptides on free-radical processes," Bull Exp Biol Med 2007 (PMID 18239817).

• [In vitro] A negative result, kept in for honesty. On mouse thymocytes, Cortagen produced no comitogenic proliferation / sphingomyelin-signalling effect, while some other peptides did — a null finding preserved here rather than smoothed over. Source: Khavinson, Rybakina, Malinin et al., "Effects of short peptides on thymocyte blast transformation and signal transduction…," Bull Exp Biol Med 2002 (PMID 12420072).

• [Patent] Developer IP. The tetrapeptide and its neurological use are covered by patent EP1224212B1 ("Tetrapeptide stimulating functional activity of neurones…," assignee the St. Petersburg Institute; inventors Khavinson, Morozov, Malinin, Grigoriev), which claims indications such as TBI, dementia, MS and cognitive impairment. A patent is a developer claim, not peer-reviewed efficacy, and it does not name the trade name "Cortagen."

Unverifiable / cautioned. Claims of a "pronounced therapeutic effect on post-traumatic recovery of peripheral nerve in humans" appear only in vendor/secondary text — no resolvable human Cortagen trial exists; do not read the rat figures as human evidence. The "penetrates the nucleus and binds DNA sequence-specifically" mechanism is the Khavinson-group model, not independently established. Any Russian marketing-authorisation/registration number for Cortagen could not be confirmed against a primary registry.

Do not conflate Cortagen with Cortexin. Studies co-testing Cortexin — the polypeptide brain-extract mixture used medically in Russia — such as Zarubina & Shabanov (Eksp Klin Farmakol 2011, PMID 21476278) and the ischemic-preconditioning paper (Bull Exp Biol Med 2016, PMID 26902350, which tests the AEDP sequence generically alongside cortexin and does not name "Cortagen") must not be reported as Cortagen-specific evidence. A widely-repeated description of Cortagen as "a porcine brain-derived peptide approved for stroke recovery" is a false conflation with Cortexin/Cerebrolysin-type extracts.

On quality. The Cortagen evidence base is thin and characteristic of the Khavinson class — single-group, preclinical, patent-adjacent, published mostly in one in-house journal, with a partly-null thymocyte result, no human clinical trial, and no independent Western replication. Its chemistry (PubChem CID 18439621) is well defined; its biology in humans is not.