F tier · safety concern
Cortagen has the largest literature in this family — around fifteen indexed papers including rat nerve-regeneration work and one non-Khavinson in vitro group in Tbilisi — but there is still no registered trial, no published human study, and the originating group's own 2014 review of clinical results omits it entirely.
Cortagen
Cortagen is a synthetic tetrapeptide (AEDP) from Khavinson's St Petersburg group, marketed as a cortical or brain 'bioregulator'. Its literature is the broadest of the five here: rat sciatic-nerve regeneration, a mouse cardiac microarray study, free-radical and chromatin-decondensation assays, and Russian-language pharmacology work on experimental brain ischaemia. All of it is preclinical, and no human study or registered trial exists.
// we supply this one
available as a research reagent
≥ 98% HPLC · lyophilised powder · batch certificate published. Grade F above is our own and is not adjusted because we stock it.
the explanation
Cortagen is a four-amino-acid peptide marketed for the brain. It has been studied more than its siblings — mainly in rats with nerve injury and in cells in dishes — but never in people, and no clinical trial has ever been registered. It is often confused with Cortexin, a different Russian brain product made from animal brain extract.
regulatory status
No medicinal approval anywhere; research reagent
Cortagen holds no marketing authorisation as a medicine in the UK, EU, or US, and there is no MHRA, EMA, or FDA record for it. A ClinicalTrials.gov query returns no registered study of Cortagen or AEDP. In Russia it is distributed within the consumer 'Cytogens' peptide range associated with Khavinson's institute; we could not verify a Russian medicines-register entry for AEDP itself, and importantly the group's own 2014 review of its bioregulators' clinical results lists Cortexin — a registered Russian polypeptide brain-extract medicine — but not Cortagen. The two should not be conflated: Cortexin is a different, non-synthetic product. UK supply is as a research reagent only, not for human consumption.
how it works · proposed mechanism
Cortagen is proposed to act as an epigenetic regulator that penetrates cells and nuclei and alters transcription of neural and other tissue-specific genes, with proline at the C-terminus assigned cortical specificity. Unusually for this family, there is also a body of chromatin-level work from a group outside the St Petersburg network. The mechanism remains characterised only in cells and rodents.
Peripheral nerve regeneration in rats
After sciatic nerve injury, Cortagen was reported to accelerate functional and structural recovery, with a persisting effect after treatment stopped. This is the most substantive in vivo signal in the family, but it is peripheral nerve rather than cortex and comes from the originating group.
Chromatin decondensation in aged cells
A Tbilisi State University group reported that Cortagen decondenses heterochromatin in lymphocytes from elderly donors, consistent with the epigenetic hypothesis. These authors are outside the Khavinson network, but the work is in vitro cytogenetics in a low-visibility specialist journal, with no functional or clinical endpoint.
Transcriptional effects across tissues
Microarray analysis in mouse heart showed differential gene expression after Cortagen exposure, and splenocyte work reported changes in interleukin-2 gene expression. These broad, cross-tissue effects sit awkwardly with the claim of strict cortical specificity.
Redox and free-radical modulation
Cortagen has been reported to affect free-radical processes in biochemical assays. Antioxidant activity in vitro is a common and non-specific finding for short acidic peptides and does not by itself indicate a neurological mechanism.
what’s reported
evidence shape
6 sourcesThe composition of the cited literature by study type. This describes the shape of the evidence, not its quality — and it does not by itself set the grade.
⚠ the catch
Cortagen is the strongest of these five and still has no human evidence at all — no registered trial, no published clinical study, no pharmacokinetics. The most persuasive finding, accelerated rat sciatic-nerve recovery, concerns peripheral nerve rather than cerebral cortex, and the only work from authors outside the St Petersburg network is in vitro chromatin cytogenetics in a low-visibility journal, which corroborates a molecular hypothesis rather than any clinical claim. The broad cross-tissue transcriptional effects reported (including in mouse heart) also undercut the marketing premise of strict cortical selectivity. Finally, Cortagen is frequently confused with Cortexin, a registered Russian brain-extract medicine with its own separate literature; borrowing Cortexin's clinical standing for Cortagen is a category error. On its own evidence Cortagen remains a preclinical research compound.
key published findings
- ClinicalTrials.gov contains no registered study of Cortagen or AEDP (verified by registry query).
- No published human study of Cortagen was located; the originating group's own 2014 review of clinical results for its peptide bioregulators does not list it.
- Sequence confirmed as Ala-Glu-Asp-Pro; chemistry verifiable via PubChem CID 18439621 — C17H26N4O9, 430.4 g/mol, CAS 335591-03-2.
- The clearest in vivo finding is accelerated functional recovery after rat sciatic-nerve injury, with a reported delayed effect after dosing ceased — peripheral nerve, not cortex.
- A Tbilisi State University group (Lezhava and colleagues, no Khavinson co-authorship) reported heterochromatin decondensation in aged human lymphocytes exposed to Cortagen — the nearest thing to independent work in this family, but in vitro only and in a low-visibility journal.
- Microarray work reported differential gene expression in mouse heart after Cortagen, which conflicts with claims of strict cortical tissue specificity.
- Cortagen is distinct from Cortexin, a registered Russian polypeptide brain-extract product; the two are frequently conflated in secondary sources.
limitations of the evidence
- No human evidence of any kind — no trial, no clinical report, no pharmacokinetics or bioavailability data.
- The principal in vivo model is peripheral nerve injury in rats, which does not test the marketed cortical or cognitive claim.
- The one non-Khavinson group publishes in vitro cytogenetics in International Journal of Peptide Research and Therapeutics and Georgian Medical News — both low-indexing venues with limited external scrutiny.
- Much primary work appears in Russian-language or Russian-translated journals (Bulletin of Experimental Biology and Medicine, Doklady Biological Sciences, Eksperimental'naya i Klinicheskaya Farmakologiya).
- Reported effects span heart, spleen and lymphocytes as well as nerve, undermining the tissue-specificity premise.
- Sources are shared with the other Khavinson bioregulators in this index because these compounds are described in one common body of literature.
documented safety signals
- No documented safety signals, but no published human safety data, no accessible toxicology package, and no adverse-event surveillance.
- Absence of reported harm reflects absence of monitored human exposure, not demonstrated safety.
- Conflation with Cortexin creates a real-world risk of users assuming a registered medicine's safety record applies to an unstudied synthetic tetrapeptide.
identity
| full name | Cortagen (Ala-Glu-Asp-Pro, AEDP) |
| category | Cognitive |
| modality | peptide |
| formula | C17H26N4O9 |
| molar mass | 430.4 g/mol |
| cas | 335591-03-2 |
| sequence | Ala-Glu-Asp-Pro (AEDP) |
laboratory handling
| storage | Lyophilised powder is stored desiccated at -20 °C and protected from light. Once reconstituted, laboratory practice is refrigeration at 2-8 °C for short-term use, or aliquoting and freezing to avoid repeated freeze-thaw cycles. Handling information only; this compound has no approved human use. |
| solubility | Short hydrophilic peptide, readily soluble in sterile or bacteriostatic water and in dilute aqueous buffer. Lot-specific solubility is stated on the certificate of analysis. |
Handling information describes laboratory practice for a research reagent. It is not a preparation guide for use in humans.
the receipts
6 citedPubChem, US National Library of Medicine · 2026 · official
ClinicalTrials.gov, US National Library of Medicine · 2026 · official
Advances in Gerontology (English translation of Uspekhi Gerontologii, Russian) · 2014 · review
Bulletin of Experimental Biology and Medicine (Russian translated journal) · 2000 · preclinical
Neuroendocrinology Letters · 2004 · preclinical
International Journal of Peptide Research and Therapeutics (low-indexing) · 2015 · preclinical
others in Cognitive