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VerifiedPeptides
Cognitive

Cortagen

Also known as: AEDP · Ala-Glu-Asp-Pro

Quick answer

Cortagen is a synthetic tetrapeptide (Ala-Glu-Asp-Pro, AEDP) developed by Prof. Vladimir Khavinson's research group as a cerebral-cortex-focused "cytogen" bioregulator — the synthesized single-sequence counterpart of Cortexin, an older natural bovine-brain-extract preparation used clinically in Russia since the 1980s. Cortagen has a moderately substantial preclinical evidence base spanning nerve regeneration, chronic cerebral ischemia, and gene-expression studies, though entirely from Khavinson-affiliated Russian research groups with no independently replicated Western clinical trial. No FDA/EMA approval exists. Research-grade material sold here is a separate product intended solely for laboratory research.

What is Cortagen?

Cortagen (Ala-Glu-Asp-Pro, AEDP) is a synthetic tetrapeptide developed by Prof. Vladimir Khavinson and colleagues at the St. Petersburg Institute of Bioregulation and Gerontology, positioned as the cerebral-cortex-focused member of the institute's "cytogen" line of single-sequence synthetic bioregulator peptides. Cortagen is specifically the synthesized single-sequence counterpart of Cortexin, an older natural extract preparation derived from cattle cerebral cortex tissue that Russian clinicians have used since the 1980s — a similar cytomax-to-cytogen relationship documented for other Khavinson compounds in this catalog, such as Vilon's relationship to the natural extract Thymalin.

Chemically, Cortagen has molecular formula C17H26N4O9, molecular weight approximately 430.4 g/mol (independently cross-checked via manual atomic-mass calculation from the formula, which matched), CAS number 335591-03-2 (cross-confirmed via a specialty chemical supplier), PubChem CID 18439621.

At Verified Peptides, we think Cortagen has a genuinely more substantial and varied preclinical research base than several other Khavinson cytogens in this catalog, spanning peripheral nerve regeneration, cerebral ischemia, and systemic gene-expression studies, described in detail below — though, as with every other Khavinson-associated compound in this catalog, this research originates entirely from Russian, Khavinson-affiliated research groups.

Peripheral nerve regeneration, one of Cortagen's more concretely studied applications, is itself a well-established, independently significant area of neuroscience and clinical research: injuries to peripheral nerves (such as the sciatic nerve, the model used in Cortagen's key study) can result in prolonged or incomplete functional recovery even after surgical repair, and this general clinical problem has motivated substantial independent research into biological and pharmacological strategies to accelerate axon regrowth and remyelination — a legitimate scientific backdrop against which Cortagen's specific nerve-regeneration finding should be understood, even though that specific finding itself remains a single-institute result.

Key Benefits & Mechanisms

Mechanism of action

Cortagen's proposed mechanism follows the general Khavinson "peptide-gene" framework: the AEDP sequence is proposed to penetrate cell and nuclear membranes and interact with regulatory regions of double-stranded DNA in cortical neurons, modulating expression of genes governing neuronal survival, synaptic remodeling, and antioxidant defense in a tissue-selective manner.

A specific, well-documented functional finding supporting a neurotrophic/regenerative research application comes from a 2000 study (Turchaninova et al., Bulletin of Experimental Biology and Medicine, PMID 11276314), which examined intramuscular Cortagen administration (10 μg/kg for 10 days) in rats following sciatic nerve transection and suturing, reporting increased nerve fiber growth rate and conduction velocity in the regenerating nerve — increases of 27% and 40%, respectively, compared to untreated controls. A related follow-up study (PMID 12134478) examined the delayed effect of Cortagen on restoration of injured nerve function. We think this peripheral-nerve-regeneration finding is a genuinely concrete, functionally-measured outcome, distinguishing it from the more abstract gene-expression-only claims made for some other Khavinson cytogens.

Separately, a 2011 study (Zarubina and Shabanov, Eksperimental'naia i Klinicheskaia Farmakologiia, PMID 21476278) examined Cortagen (alongside Cortexin, its natural-extract predecessor) in a rat model of chronic cerebral ischemia, reporting that Cortagen accelerated recovery of disturbed individual behavior in ischemic rats with varying hypoxia resistance, and that both compounds reduced excessive lipid peroxidation and supported antioxidant activity in brain tissue — again, a functional behavioral outcome alongside a biochemical antioxidant mechanism.

Chronic cerebral ischemia, the condition modeled in this study, refers to sustained, long-term reduction in brain blood flow (distinct from an acute stroke event), which is independently recognized in mainstream neurology as a contributor to vascular cognitive impairment and vascular dementia. Lipid peroxidation — the oxidative degradation of cell-membrane lipids that the Zarubina/Shabanov study measured — is a well-established, independently studied marker of oxidative cellular damage used broadly across neuroscience research, giving this specific finding a connection to established, checkable biochemistry rather than a purely proprietary measure.

Research Summary

At Verified Peptides, we think Cortagen has one of the more methodologically varied preclinical evidence bases among the Khavinson cytogens in this catalog, spanning at least three genuinely distinct experimental models, and we want to describe this honestly alongside its real limitations. Beyond the nerve-regeneration and cerebral-ischemia studies described above, a 2004 study (Anisimov, Khavinson, and Anisimov, Neuro Endocrinol Lett, PMID 15159690) examined Cortagen's effects on gene expression in mouse heart tissue using microarray analysis of approximately 15,000 transcripts, reporting significant expression changes in 234 clones matching 110 known genes across various functional categories, with fold-changes ranging from 5.42-fold upregulation to 2.86-fold downregulation. We think it is worth noting directly that this is a somewhat unusual study for a compound whose primary research framing is cerebral-cortex-specific — testing a "brain cortex peptide" for effects on cardiac gene expression — which the original authors appear to have undertaken specifically to examine whether Cortagen's effects extend, or are limited to, its primary target tissue.

We want to be equally direct about this evidence base's real limitations: every study described above originates from Khavinson-affiliated Russian research groups, and we are not aware of any independent replication by researchers outside this network, nor any registered or published Western randomized controlled human clinical trial. Secondary sources describe reported human clinical use of Cortagen (and its natural-extract predecessor Cortexin) for nerve recovery and cerebrovascular parameters in Russian clinical settings, but we could not independently verify the specifics of these human studies against checkable, indexed primary sources with the same confidence as the animal studies cited above. We think it is worth directly comparing Cortagen's evidence profile to the other Khavinson cytogens built across this catalog: it is more substantively documented than Cardiogen and Crystagen (for which little to no dedicated research was located), roughly comparable in depth to Vilon, Chonluten, and Pinealon (each with a handful of specific, real studies), but still meaningfully behind genuinely independent, multi-group, internationally-published compounds such as Thymulin or Nesiritide. Researchers should calibrate their confidence in any specific Cortagen claim accordingly, weighing the real functional findings described above against the single-network origin of all of them.

No FDA, EMA, or other Western regulatory body has evaluated or approved Cortagen for any indication. At Verified Peptides, we sell research-grade Cortagen exclusively for laboratory research, and we think its combination of a specific, functionally-measured nerve-regeneration finding, a cerebral-ischemia behavioral study, and a genuinely distinct gene-expression investigation gives it a moderately more substantial (though still entirely single-network) evidence base than several other Khavinson cytogens built in this catalog.

Common Stacks

Cortagen and Semax At Verified Peptides, we see Cortagen and Semax as two CNS-focused peptides with Russian research origins, studied for neuroprotective and cognitive-support research through different mechanisms — Cortagen via proposed gene-regulatory effects in cortical neurons and documented nerve-regeneration/antioxidant findings, Semax via effects linked to BDNF and NGF expression. Researchers studying this broader category of Russian-origin neuroprotective peptides may find this pairing useful for comparing these distinct mechanistic and evidentiary profiles. Cortagen and Selank At Verified Peptides, we note that Cortagen and Selank are both CNS-active peptides from the broader Russian peptide-bioregulator research tradition, though Selank's research centers on GABAergic/anxiolytic mechanisms while Cortagen's centers on cortical gene regulation, nerve regeneration, and ischemic neuroprotection. Researchers examining this general research space may find this pairing useful for contrasting these different mechanistic research directions. Cortagen and Pinealon At Verified Peptides, we see Cortagen and Pinealon as two Khavinson cytogens sharing the same general tissue-selective gene-regulation research framework applied to CNS tissue, with Cortagen focused on cerebral cortex (nerve regeneration, ischemic neuroprotection) and Pinealon focused more broadly on oxidative-stress protection across multiple cell types. Researchers examining this bioregulator research program's internal consistency across CNS-relevant compounds may study the two together, noting each compound's distinct specific evidence base.

Lesser-Known Facts About Cortagen

Cortagen's relationship to Cortexin — the older natural bovine-brain-extract preparation it was synthesized to replicate in single-sequence form — mirrors a pattern seen elsewhere in this catalog's Khavinson-associated compounds (Vilon from Thymalin, Thymogen also from Thymalin), where a natural tissue extract used in earlier Russian clinical practice was later fractionated to identify and synthesize its proposed active peptide fragment as a standalone compound.

The 2011 chronic cerebral ischemia study's finding that Cortagen's effects were specifically studied across rats with "different resistance to hypoxia" reflects a genuinely more sophisticated experimental design than a simple treated-versus-untreated comparison, since it examined whether Cortagen's effects depended on the animals' baseline physiological resilience to oxygen deprivation — a nuance relevant to researchers interested in whether a compound's neuroprotective effects are uniform across different baseline vulnerability profiles.

The nerve-regeneration study's reported outcome measures — nerve fiber growth rate and conduction velocity — are both standard, independently established electrophysiological and histological measures used broadly in peripheral nerve injury research, not measures unique to Khavinson's research program, lending some methodological credibility to how that specific study's findings were measured even though the study itself was not independently replicated.

Cortagen's inclusion in a mouse cardiac gene-expression study, despite being developed and marketed as a brain-specific compound, illustrates a broader, honest point about tissue-selectivity claims across the Khavinson cytogen catalog: even compounds marketed around a specific target organ may show measurable effects in other tissues when directly tested, which is either evidence against strict tissue-selectivity or evidence of genuinely broader systemic activity, depending on interpretation — a nuance not always reflected in commercial marketing framing built around a single target organ.

Purity & Sourcing Considerations

At Verified Peptides, we require independent third-party HPLC purity testing and mass spectrometry identity confirmation for every batch of research-grade Cortagen we offer, with a Certificate of Analysis (COA) available for each lot. As a four-residue peptide, Cortagen is straightforward to synthesize to high purity using standard solid-phase peptide synthesis methods.

We source exclusively from manufacturers operating under Good Manufacturing Practice (GMP)-aligned quality systems, and every lot is independently verified rather than accepted solely on a supplier's internal documentation. Researchers should always request and review the specific COA for the lot they receive, confirming purity percentage and molecular identity before use in any experimental protocol.

Storage & Stability

Lyophilized Cortagen is stable when stored at -20°C, protected from light and moisture, and researchers can generally expect the unreconstituted peptide to maintain integrity over an extended period under these conditions. At Verified Peptides, we ship lyophilized peptide with appropriate cold-chain packaging to preserve stability in transit.

Once reconstituted with bacteriostatic water or another appropriate sterile diluent, Cortagen solution should be stored refrigerated at 2–8°C and used within the timeframe indicated on the product's documentation. As with other short peptides in this catalog, reconstituted solutions are generally less stable than the lyophilized form and more susceptible to degradation and microbial contamination with repeated freeze-thaw cycling.

Researchers should avoid repeated freeze-thaw cycles of reconstituted material and should follow the specific storage guidance provided with each lot's documentation to preserve sample validity for research use.

Frequently asked questions about Cortagen

What is Cortagen and what is it studied for?

Cortagen (AEDP, Ala-Glu-Asp-Pro) is a synthetic tetrapeptide developed by Khavinson's research group as a cerebral-cortex-focused bioregulator, studied for peripheral nerve regeneration, cerebral ischemia recovery, and gene-expression effects.

What is the strongest evidence for Cortagen?

A 2000 study (PMID 11276314) found Cortagen increased nerve fiber growth rate (27%) and conduction velocity (40%) after sciatic nerve injury in rats. A 2011 study (PMID 21476278) found it accelerated behavioral recovery and reduced oxidative damage in a chronic cerebral ischemia rat model. Both are real, functionally-measured outcomes from Khavinson-affiliated Russian research groups.

What is the relationship between Cortagen and Cortexin?

Cortexin is an older natural extract derived from cattle cerebral cortex tissue, used in Russian clinical practice since the 1980s. Cortagen is the synthesized, single-sequence tetrapeptide counterpart developed later, identified as a proposed active fragment of the natural extract — the same general relationship pattern seen between Vilon and its natural-extract predecessor Thymalin.

Is Cortagen's research independently replicated outside Russia?

No. All located Cortagen studies originate from Khavinson-affiliated Russian research groups. We are not aware of independent replication by outside research groups or any Western randomized controlled human clinical trial.

Is Cortagen FDA approved?

No. Cortagen has not been evaluated or approved by the FDA, EMA, or any other Western regulatory body for any indication. It remains an investigational research compound.

Why was a 'brain cortex peptide' tested for effects on the heart?

A 2004 study (PMID 15159690) specifically examined whether Cortagen's effects extend beyond its primary target tissue, using microarray analysis of mouse cardiac gene expression. It found significant changes in 110 known genes, illustrating that even organ-specific-marketed cytogens can show measurable effects in other tissues when directly tested.

What is the proposed mechanism behind Cortagen's effects?

Cortagen is proposed to penetrate cell and nuclear membranes and interact with DNA regulatory regions in cortical neurons, modulating expression of genes governing neuronal survival, synaptic remodeling, and antioxidant defense, following the general Khavinson cytogen 'peptide-gene' framework.

What administration route has been used in Cortagen research?

Published rodent research has used intramuscular injection. This describes methodology used in published research, not usage instructions — Verified Peptides does not provide dosing guidance for human or animal administration.

How does Cortagen's evidence base compare to other Khavinson peptides in this catalog?

Cortagen is more substantively documented than Cardiogen and Crystagen (for which little to no dedicated research was located), roughly comparable to Vilon, Chonluten, and Pinealon, but still behind genuinely independent, multi-group, internationally-published compounds like Thymulin or Nesiritide. All of its evidence originates from Khavinson-affiliated Russian research groups.

Legal & research status: Cortagen has not been approved by the FDA, EMA, or any other Western regulatory body for any human or animal indication, and no independently verified Western randomized controlled human clinical trial has been located for the compound as of 2026. Material sold as a research peptide is offered strictly for laboratory and research use, not for human consumption or therapeutic use.

Research use only All content is provided for informational and research purposes only and is not medical advice. Peptides referenced are sold and discussed for laboratory and research use only, not for human consumption. Consult a licensed physician before making any health decision.