CognitiveAEDPAla-Glu-Asp-Pro

Cortagen (AEDP)

Khavinson 'Cytogen' synthetic tetrapeptide · derived from the Cortexin brain-cortex extract · single-school evidence

Cortagen is a synthetic tetrapeptide — four amino acids, Ala-Glu-Asp-Pro (AEDP) — from the 'Cytogen' line of short 'peptide bioregulators' developed by Vladimir Khavinson and the St. Petersburg Institute of Bioregulation and Gerontology in Russia. An important distinction up front: Cortagen is a single, defined molecule, not an extract. It was created by directed synthesis from the amino-acid analysis of Cortexin, a complex preparation of cattle brain-cortex peptides — so Cortagen is the small synthetic peptide derived from Cortexin, and the two should not be confused. Within the Cytogen family it is positioned as the brain-cortex peptide, marketed for neuroprotection, nerve regeneration and cognition. The chemistry is a little awkward to pin down: the name does not resolve in the main chemical database, and the molecule is found only as a structure record with undefined stereochemistry — so its formula and weight belong to that structure entry rather than to a curated drug record, and it carries no CAS or UNII. The biology is the familiar single-school picture. Essentially all the evidence comes from Khavinson's network and its long-standing Tbilisi collaborators, published mostly in the school's own Russian-language journals, with no independent Western replication and no regulatory approval. The neuroprotective and nerve-regenerative claims rest on small rodent and cell studies plus a single descriptive gene-expression screen that was actually done in heart tissue, not brain. The honest framing: an experimental Russian-school research peptide with preliminary, non-replicated evidence — not a proven brain therapy.

The short version

Cortagen is a trade name for AEDP, a synthetic peptide of four amino acids (alanine, glutamic acid, aspartic acid, proline). It comes from the Russian 'Cytogen' family of tiny 'bioregulator' peptides designed by Vladimir Khavinson's group. It is worth getting one thing straight immediately: Cortagen is a single, well-defined little molecule — it is not the same thing as Cortexin. Cortexin is a complex extract of cattle brain-cortex peptides; Cortagen is the short synthetic peptide that was designed from analysing Cortexin. People sometimes mix the two up.

Cortagen's assigned tissue is the brain cortex, and it is marketed for neuroprotection, nerve repair and cognition. The chemistry is slightly fiddly: the name 'Cortagen' doesn't come up in the main chemical database, and the molecule only appears there as a structure with its 3D shape left undefined — so the listed formula and weight come from that structure entry, not from a polished drug record, and there's no CAS or registry number.

On the biology, this is the familiar pattern for this family. Almost all the research is from Khavinson's network and a long-time collaborating lab in Tbilisi, published mostly in the school's own Russian journals, with no independent Western team reproducing it. The nerve-regeneration and neuroprotection claims rest on small rat and cell studies, plus one gene-activity screen that — notably — was run in heart tissue rather than brain. So Cortagen is best understood as an experimental research peptide with preliminary, unreplicated evidence, not a proven brain or nerve treatment.

Molecular identity

Specs

Molecular weight: 430.4 g/mol (structure-record value)
UNII: Unverified — not asserted

Sequence (4 AA): Ala-Glu-Asp-Pro (AEDP) — defined synthetic tetrapeptidePMID 15159690 (Anisimov 2004); NCBI MeSH UI 67431545
Structure / class: Synthetic tetrapeptide derived from the Cortexin brain-cortex extract; Khavinson 'Cytogen' bioregulatorPMID 15159690; Khavinson-school literature
Molecular formula: C₁₇H₂₆N₄O₉ (structure-record value, undefined stereo)PubChem CID 17906670 (flat connectivity structure)
Monoisotopic mass: 430.16998 Da (structure-record value, undefined stereo)PubChem CID 17906670
InChIKey: PLTRIMAUDDQYRV-UHFFFAOYSA-N (undefined-stereo structure)PubChem CID 17906670
CAS number: Unverified — not assertedNo CAS in PubChem xrefs for CID 17906670
PubChem record: CID 17906670 (structure only; name 'Cortagen' does not resolve by name — PUGREST.NotFound)PubChem
Water solubility: Highly water-soluble (computed XLogP −6.5)PubChem CID 17906670 (computed)
Molecular target: No classic receptor; claimed brain-cortex/CNS gene-expression modulator (neuroprotection, nerve regeneration) — single-school positioning; one microarray screen was in mouse heart, not brainKhavinson-school 'tissue-specific peptide' framework
Half-life: Not established (no published human pharmacokinetic data; only an animal research dose exists)Not established
Regulatory status: Not approved by any major drug regulator; no independent Western trials locatedNo NDA/BLA/EMA record located

Plain English

Mechanism

The Khavinson framework holds that ultra-short peptides penetrate cells and nuclei, bind specific DNA or chromatin sites, and act as transcription modulators — 'tissue-specific' geroprotectors that normalise age-altered gene expression. Cortagen is positioned as the brain-cortex-specific member of the family, with claimed downstream effects that are neurotrophic, neuroprotective in ischemia, antioxidant and immunomodulatory.

It needs to be said plainly: this gene-regulation paradigm is a single-school hypothesis. The direct DNA-binding / transcription-factor mechanism has not been demonstrated for Cortagen specifically — it is extrapolated from the broader Khavinson peptide-DNA model, which itself remains contested and largely unreplicated by independent structural and biophysical groups.

What has actually been shown is narrower and, in one key respect, off-target. Cortagen altered the expression of roughly 110 genes in mouse heart in a cDNA-microarray screen — but that is a single descriptive transcriptome snapshot, and it was in heart, not cortex. In rats, it was reported to speed sciatic-nerve regeneration and improve nerve-conduction measures. These are real reported effects in animal models, but they are a long way from a validated, brain-specific gene-regulatory mechanism, and the descriptive gene screen does not establish the proposed direct-DNA-binding action.

Sources:PMID 15159690 PMID 11276314 PMID 11713572

Why people reach for it

Potential benefits

Cortagen (AEDP) is the Khavinson family's brain-cortex peptide, derived from the Cortexin extract. Here's what draws people to it — kept modest, because the evidence is small rodent and cell studies from a single research network, not human proof.

A nerve-repair angle people pursue — Cortagen's most concrete result is in rat sciatic-nerve studies, where it was reported to speed nerve regeneration and improve nerve-conduction measures — which is why it's reached for in pursuit of nerve recovery, with the caveat that this is rodent work, not human data.
Neuroprotection and daytime-cognition interest — Marketed as a cortical neuroprotectant, it's used in pursuit of clearer daytime thinking and brain resilience; a rat chronic-cerebral-ischemia study described it as a corrector of brain metabolic disorders — an early-stage signal from a school-affiliated group.
The brain-cortex tile of the bioregulator set — Within Khavinson's one-peptide-per-tissue concept, Cortagen is the cortex-assigned member, which is why users add it when the goal is cortical/cognitive support specifically.
Pairs with a better-evidenced nootropic — It's commonly stacked with Semax, which carries a stronger independent base for BDNF and neurotrophic support — Cortagen is positioned as the cortical-bioregulator layer alongside it, judged mostly on Semax's evidence.
Runs as a short, defined course — Like the rest of the family, Cortagen is used in brief pulsed courses (around 5–10 days) rather than daily indefinitely — a contained pattern that fits the bioregulator approach.

Sources:PMID 11276314 PMID 12134478 PMID 21476278

What people reach for Cortagen for, drawn from what the research reports (single-school, rodent and cell only) and how it's used — not proven human outcomes or medical claims.

Implied timing

Best time to dose

Implied best time

Morning (or consistent)

Most people take Cortagen in the morning, leaning on its daytime-cognition positioning — but a consistent daily time matters more than the exact hour.

Cortagen is marketed as a cortical neuroprotectant aimed at daytime cognition and mental clarity, so a morning dose lines the peptide up with the part of the day people actually want that effect.
There's no circadian or pineal logic pulling it toward the evening (unlike Epitalon or Pinealon), so morning is simply the sensible default for a cognition-oriented compound rather than a mechanistic requirement.
No published chronobiology or human pharmacokinetic data exist for Cortagen, so timing is reasoned from how it's used, not from the clock — which is why consistency across the short course matters more than the precise hour.
Cortagen is run in short pulsed courses (around 5–10 days), so holding the same daily slot through the course is the practical priority.

No study establishes an ideal time of day for Cortagen — this is reasoned from its daytime-cognition positioning and how it's used. As a rule of thumb most peptide dosing lands in the midday-to-evening window; for Cortagen the lean is morning, with consistency the real point.

How to run it

Dosing & protocol

Cortagen is used here as a subcutaneous injection — the form sold as a research peptide and the route the on-page calculator is built for. One honest fact upfront: no published human dose exists. The only citable experimental figure is a rodent research dose (10 µg/kg IM × 10 days in rats). The ranges and schedule below are community convention among Khavinson-bioregulator users, not a human trial protocol. Read them as a map of how people actually run injectable Cortagen — not a validated prescription.

Single-school evidence + no human dose: Cortagen's entire evidence base is rodent and cell work from one research network. There is no published human dose, no human trial, and no independent Western replication. Every number here is usage convention, not trial data — and this peptide's thin evidence makes that caveat heavier than for most.

Dose — no established human dose

The only quantitatively citable dose is a rodent research figure. Community convention fills the gap.

Rodent reference (not a human protocol):: 10 µg/kg intramuscularly once daily for 10 days in rats (Turchaninova 2000, PMID 11276314) — an animal-model dose used to produce a nerve-regeneration readout. Do not convert this to a human dose; it is not validated for that purpose.
Community convention (SubQ):: Longevity and Khavinson-bioregulator communities report short courses of 0.1–0.5 mg subcutaneously daily for 5–10 days. This is unverified vendor/community convention with no clinical backing — treated here as 'how people actually run it,' not as evidence.
Route:: Subcutaneous injection. The rodent studies used IM; SubQ is the practical research-peptide convention.

Subcutaneous administration

Cortagen is injected into subcutaneous fat; site, rotation, and timing are the actionable choices.

Injection site:: Abdomen (staying a couple of inches clear of the navel), the outer thigh, or the love-handle area. Rotate sites between doses to prevent local irritation and fatty lumps (lipohypertrophy).
Measuring the dose:: Drawn on a U-100 insulin syringe from the reconstituted vial. The reconstitution card below converts each dose to syringe units — at the standard mix of 10 mg + 2 mL BAC water (5,000 mcg/mL), 100 mcg = 2 IU · 250 mcg = 5 IU · 500 mcg = 10 IU. The on-page calculator adjusts for any vial size.
Time of day:: Morning is the conventional choice for daily Cortagen dosing among longevity users — see Best time to dose above. No published timing rationale exists for Cortagen specifically, but morning fits its daytime-cognition positioning; a consistent daily time across the short course matters more than the exact hour.
Food window:: Subcutaneous Cortagen is independent of meals; no food-window restriction applies.

Cycle & washout

Khavinson-family peptides are characteristically run as short, pulsed courses — the school's own protocols use this pattern.

Standard course:: 5–10 days of daily subcutaneous use, consistent with the rodent study design and Khavinson-school convention for short bioregulator courses.
Repeat interval:: Khavinson protocols conventionally repeat courses every 3–6 months. No washout rationale from human pharmacokinetics exists — this is the school's empirical pattern.
Why short courses:: The peptide-bioregulator framework posits transient gene-modulating action; prolonged continuous use is not modeled in any published study. Short pulsed courses are what the evidence base (however thin) actually used.

Reconstitution at a glance

The on-page calculator does this live; quick reference for a 10 mg vial + 2 mL BAC water:

Mixing:: 10 mg vial + 2 mL bacteriostatic water = 5,000 mcg per mL. On a 100-unit (1 mL) insulin syringe: 100 mcg = 2 IU · 250 mcg = 5 IU · 500 mcg = 10 IU · 1,000 mcg = 20 IU.
Why 2 mL:: Matches the calculator's default for this vial size. The resulting concentration keeps small microgram doses measurable on a standard insulin syringe without microscopic increments.

Sources:PMID 11276314 PMID 15159690

Substrate the signal needs

Nutritional cofactor precision

Cortagen has no cofactor research of its own. These cards are reasoned from what it proposes to do — a brain-cortex neuro-bioregulator marketed for neuroprotection and nerve repair — matched to the nutrients brain and nerve tissue actually run on. Three questions drove the grouping: what substrate does the proposed action need? what amplifies brain health independently? what could mitigate any downside?

Mechanistic reasoning applied to a single-school hypothesis — not a Cortagen cofactor study. Every compound and dose below is community range for general brain/nerve support, not a Cortagen-specific finding. The caveats on Cortagen itself apply here too: the underlying mechanism is unproven.

Supply the neuro substrate (omega-3 DHA · B-vitamins · protein)

If Cortagen acts on brain and nerve tissue at all, these are the raw materials it would need.

Omega-3 DHA:: 2–3 g combined EPA/DHA daily (fish oil or algal DHA). DHA is the long-chain fat the brain is structurally built from and that nerve membranes require for repair and plasticity. This is the single most evidence-backed nutritional input for brain and nerve health.
B6 / B9 / B12:: B12 500–1,000 mcg (methylcobalamin preferred), folate (B9) 400–800 mcg, B6 1–2 mg — taken with food. These three are required for myelin sheath integrity and healthy nerve signalling; a deficiency in B12 or folate produces real neurological damage on its own, making them foundational rather than optional.
Adequate dietary protein:: Any peptide is made of amino acids, and nerve repair draws on them. ~1.6–2.2 g/kg bodyweight daily — not a supplement, just the basic substrate Cortagen (and every peptide) is built from and any nerve tissue synthesis would draw on.

Amplify — BDNF & glymphatic support (exercise · sleep · magnesium)

The most evidence-backed cofactors for brain health are lifestyle inputs, not supplements.

Aerobic exercise:: 20–45 min moderate-intensity cardio 4–5×/week is the single most robust driver of BDNF (brain-derived neurotrophic factor — the brain's own growth and repair signal). BDNF has far stronger evidence for neuroprotection than Cortagen does; exercise is the foundation, not an add-on.
Sleep (7–9 hours):: Glymphatic clearance — the brain's overnight waste-removal system — runs almost entirely during sleep. Chronic poor sleep impairs every neuroprotective process. If Cortagen does anything for brain health, it is built on top of this, not a substitute for it.
Magnesium glycinate or threonate:: 200–400 mg magnesium glycinate nightly (or magnesium L-threonate 1.5–2 g for the brain-penetrant form). Magnesium gates NMDA receptor activity, supports nerve-signal transmission, and many people run chronically low — a deficiency impairs every neurotransmitter system.

Mitigate — antioxidant buffer (vitamin C · E · polyphenols)

Cortagen's claimed profile includes antioxidant effects; supporting the nervous system's antioxidant baseline is the logical cofactor for any neuroprotective peptide claim.

Vitamin C:: 500–1,000 mg/day. The nervous system is metabolically active and oxidative-stress-prone; vitamin C is the primary water-soluble antioxidant maintaining neuronal redox balance.
Vitamin E (mixed tocopherols):: 200–400 IU/day with food. The fat-soluble antioxidant protecting nerve-cell membranes — works in combination with vitamin C, not redundantly.
Polyphenol-rich diet:: Colourful plants (berries, leafy greens, dark chocolate, green tea) deliver a broad polyphenol spectrum that independently supports NF-κB modulation and neuroinflammation control. No precise dose — dietary pattern matters more than any single extract.

Combinations + timing

Stacking notes + timing windows

Cortagen is a Khavinson-school neuro-bioregulator with claimed brain-cortex targeting. The most useful pairings come at the same broad goal from a meaningfully different angle — a better-evidenced neurotrophic agent, or another Khavinson tissue-specific peptide. Cortexin is mentioned here only to distinguish it from Cortagen (extract vs defined tetrapeptide), not as a stack partner.

All Cortagen stacks are doubly speculative: Cortagen itself has only thin single-school rodent evidence and no human dose, so any stack inherits that uncertainty on top of the general 'combination not studied' caveat. Community convention only — not a validated protocol.

Cortagen + Semax

The most defensible neuro pairing — Semax brings meaningfully better BDNF/neurotrophic evidence to complement Cortagen's proposed cortical-bioregulator action.

Why it works:: Semax (a synthetic ACTH(4-7) analog) has documented BDNF upregulation and neuroprotective data in multiple independent rodent models, plus some human clinical work in Russia — considerably better than Cortagen's evidence base. Semax targets BDNF-pathway neurotrophin support; Cortagen is proposed to work through a gene-modulation route. Two different levers on brain-cortex health rather than the same one twice.
The protocol:: Cortagen by SubQ injection (community convention: 0.1–0.5 mg daily, 5–10 day course) + Semax intranasally (community convention: 300–600 mcg/day intranasally in split doses). Run the two courses together or in sequence. Semax is the anchor here — its evidence base is substantially stronger.
Outcome:: The pairing users reach for when combining a Khavinson-school short bioregulator with a better-studied Russian nootropic peptide for general cognitive and neuroprotective goals.

Cortagen + Pinealon

Same-family Khavinson stacking — Pinealon is the pineal / anti-aging short peptide; Cortagen covers the brain-cortex tissue slot.

Why it works:: Pinealon (Glu-Asp-Arg, another Khavinson Cytogen tripeptide) is positioned as a pineal/neurological geroprotector; Cortagen covers brain-cortex neuroprotection. The Khavinson framework runs them together on 'tissue-specific bioregulator' logic — different molecular targets, same research network. Flag: stacking two single-school bioregulators with thin, non-replicated evidence multiplies the speculation. This is community pattern, not a validated two-peptide protocol.
The protocol:: Short co-courses: Cortagen 0.1–0.5 mg SubQ + Pinealon 0.1–0.5 mg SubQ, once daily for 5–10 days. Both on the same Khavinson short-course / repeat-quarterly convention. Doses are community convention — neither has a published human dose.
Outcome:: Used in longevity and Khavinson-bioregulator communities for broad neuro/cognitive geroprotection. Honest framing: two speculative peptides from the same school, stacked on unproven shared framework — the evidence does not compound, the speculation does.

Cortagen vs Cortexin — a distinction, not a stack

Cortexin is the brain-cortex extract Cortagen was derived from. They are not the same compound and are not meaningfully stacked.

The distinction:: Cortexin is a complex multi-peptide extract of bovine brain cortex — a mixture of many peptides, used clinically in Russia and some Eastern European countries. Cortagen (AEDP, Ala-Glu-Asp-Pro) is the single synthetic tetrapeptide isolated and then synthesized from the amino-acid analysis of Cortexin. One molecule vs a complex mixture. They share a lineage, not an identity.
Why they are not stacked:: Cortexin already contains AEDP-like peptides within its mixture. Combining the defined synthetic tetrapeptide with the extract from which it was derived adds no complementary mechanism — it would just be partial overlap on the same already-speculative pathway. The two are discussed together only to clarify this distinction.

Reconstitution math

Reconstitution calculator

Calculated for a 1 mL U-100 insulin syringe (100 units/mL).

Peptide per vial

BAC water added

Desired dose

Units per dose

Draw to this mark on a U-100 syringe

Volume per dose: 0.2 mL
Doses per vial: 10
Concentration: 5 mg/mL

One vial lasts

Daily: 10 days
Every other day: 20 days
5×/week: 14 days

Research use only. Not for human consumption. Outputs are reference values based on research literature — verify all measurements independently.

From the studies

Side effects from research

There is no meaningful human safety database for Cortagen. The research is rodent and cell work, which cannot characterise side effects, rare events, or long-term risk in people. Absence of reported harm in such studies is not the same as a demonstrated safety profile.

Within those animal and cell models the peptide was generally described as well tolerated, but total human exposure in controlled settings is effectively zero, so nothing can be said with confidence about safety at any dose, over any duration.

Gray-market sourcing adds purity and identity risk independent of the peptide. The honest summary: Cortagen's human safety is uncharacterised, not established.

Sources:PMID 11276314

As reported in literature

Research dosing ranges

These are experimental designs from rodent and cell studies — all from the Khavinson network and its Tbilisi collaborators — shown for reference only. The one quantitative dose (10 µg/kg, rats) is an animal research dose, not a human protocol. There is no human dose, no approved regimen, and no independent Western replication.

Dose	Route	Model	Outcome	Sources:
10 µg/kg daily ×10 d	IM (rats)	Rat sciatic-nerve regeneration (Turchaninova 2000, Bull Exp Biol Med)	Reported increased sciatic-nerve growth rate (~+27%) and conduction velocity (~+40%) — a rodent nerve-regeneration signal, not a clinical outcome	PMID 11276314
In vivo	In vivo (rats)	Injured-nerve functional restoration (Kolosova 2002, Doklady Biological Sciences)	Reported a delayed effect of Cortagen on functional restoration of an injured nerve — an animal recovery signal	PMID 12134478
In vivo	Microarray (mouse)	Mouse heart cDNA-microarray gene screen (Anisimov 2004, Neuro Endocrinol Lett)	Altered expression of ~110 genes — a single descriptive transcriptome screen, and notably in heart, not brain; this is the paper that defines Cortagen = Ala-Glu-Asp-Pro from Cortexin	PMID 15159690
In vivo	In vivo (rats)	Chronic cerebral ischemia, brain metabolic correction (Zarubina 2011, Eksp Klin Farmakol)	Cortexin and Cortagen reported as correctors of brain metabolic disorders in chronic ischemia — a rodent neuroprotection signal from a school-affiliated group	PMID 21476278

Quick answers

Frequently asked

What is Cortagen, and is it the same as Cortexin?

No — they are different. Cortagen is a single defined synthetic tetrapeptide (Ala-Glu-Asp-Pro) from Vladimir Khavinson's Russian 'Cytogen' line. Cortexin is a complex extract of cattle brain-cortex peptides. Cortagen was designed from the amino-acid analysis of Cortexin, but it is one molecule, not the extract.

Does Cortagen protect the brain or regenerate nerves?

That is not established in people. The evidence is small rodent studies (sciatic-nerve regeneration, cerebral-ischemia models) and a single gene-expression screen that was actually run in heart tissue — all from Khavinson's network and its Tbilisi collaborators, with no independent Western replication and no human trials. Treat the neuroprotective and nerve-repair claims as hypotheses, not facts.

Why is the chemistry described as uncertain?

The name 'Cortagen' doesn't resolve in the main chemical database, and the molecule appears only as a structure record with undefined 3D stereochemistry. So the listed formula (C₁₇H₂₆N₄O₉) and weight (430.4 g/mol) are structure-record values, not a curated drug entry, and there is no CAS or UNII. The sequence itself, though, is primary-sourced in the literature.

Is there a known dose?

There is no human dose. The only quantitative figure is a rodent research dose — 10 µg/kg intramuscularly once daily for 10 days in rats — reported for reference only, not as a human protocol. Any vendor mg amounts or 'courses' are unverified.

Is Cortagen approved or independently validated?

No. It is not approved by any major drug regulator, and no independent Western group has reproduced the findings. The most recent paper (a 2023 Tbilisi study) is from a long-standing Khavinson collaborator, not an independent replication.

Primary sources

References

PMID 11276314Turchaninova LN et al., Bull Exp Biol Med 2000 — IM Cortagen 10 µg/kg ×10 d increased sciatic-nerve growth rate (~+27%) and conduction velocity (~+40%) in rats
PMID 12134478Kolosova LI et al., Doklady Biological Sciences 2002 — delayed effect of Cortagen on functional restoration of an injured nerve (rat)
PMID 15159690Anisimov SV et al., Neuro Endocrinol Lett 2004 — microarray: Cortagen altered ~110 genes in mouse heart; defines Cortagen = Ala-Glu-Asp-Pro from Cortexin
PMID 11713572Khavinson VK et al., Bull Exp Biol Med 2001 — tissue-specific effects of short peptides (school mechanism framing)
PMID 21476278Zarubina IV et al., Eksperimental'naia i Klinicheskaia Farmakologiia 2011 — Cortexin & Cortagen as correctors of brain metabolic disorders in chronic ischemia (rat)
PubChem CID 17906670PubChem structure record — connectivity structure (undefined stereo); name 'Cortagen' does not resolve by name. Formula/MW are structure-record values

Research use only · Not medical advice · Updated 2026-06-01