Research and informational content only. Not medical advice. Many peptides discussed on this site are not approved for human use.
Pinealon
Khavinson BioregulatorAlso known as: EDR peptide · Glutamylaspartylarginine · T-33 peptide · Pinealon cytogen
Animal Only
Pinealon is a plausible-sounding Khavinson-designed tripeptide backed by roughly three decades of output from a single St. Petersburg research network, with no independent Western replication. The evidence is limited to animal and in vitro preclinical studies. The Trofimova 2015 paper from the same network reported prooxidant activity and CD34+ hematopoietic suppression, a countersignal vendor marketing omits.
Countersignal from inside the same research network
Trofimova 2015, a paper from the same Khavinson network that produced essentially every Pinealon study, reported prooxidant activity and CD34+ hematopoietic cell suppression with Pinealon. This directly contradicts the "antioxidant" positioning in consumer marketing and is rarely mentioned by vendors.
For laboratory research use only. Not for human or animal consumption.
Evidence Tier
Animal Only
Mol. Weight
418.4 Da
Last Reviewed
Apr 19, 2026
Claimed benefits by evidence tier
Column header colour matches the tier
Animal Only6
- Neuroprotection against oxidative and excitotoxic stress
- Improvement of learning and memory in animal aging models
- Alzheimer-relevant neuroprotection (dendritic spine preservation)
- Huntington's disease neuroprotection
- Telomere lengthening / geroprotection
- Irisin / "exercise mimetic" effect
Unsupported3
- Circadian rhythm / sleep / "pineal function restoration"
- "Anti-Alzheimer's," "reverses aging," "treats Parkinson's / MS / encephalopathy"
- Oral bioavailability enabling at-home "nootropic" effects
About this peptide
Plain English
Pinealon is a very short synthetic peptide, just three amino acids glued together, designed by Russian researcher Vladimir Khavinson and his group in St. Petersburg. It is one of a larger family of "short peptide bioregulators" they developed and marketed in Russia as dietary supplements. The theory behind it is that the peptide is small enough to slip inside cells and even the cell nucleus and influence which genes turn on, particularly in the brain. The evidence behind these claims comes from rats, mice, and cells in a dish, with no independent Western replication.
Technical
Pinealon is the tripeptide Glu-Asp-Arg (EDR), one of several "cytogen" short peptides generated by the Khavinson laboratory by fragmenting bovine/porcine brain cortex extracts (Cortexin) and synthesizing the proposed active sequence. The literature proposes a non-receptor mechanism: EDR is thought to enter cells and nuclei directly (shown in HeLa cells with FITC-labeled peptide), bind preferentially to d(CCTGCC)/d(CCAGC)/CNG and CAG-containing motifs in the major groove of dsDNA, and modulate transcription of genes relevant to antioxidant defense (SOD2, GPX1), apoptosis (CASP3, p53), PPAR signaling (PPARA, PPARG), and monoamine synthesis (TPH1). Virtually all functional evidence is from the Khavinson group and collaborators, published mostly in Russian journals (Bull. Exp. Biol. Med., Adv. Gerontol.) with limited peer-reviewed international replication. The evidence base is limited to animal and in vitro studies with no independent replication outside the originating institute network.
Mechanism of action
Cell and nuclear penetration
FITC-labeled Pinealon labels cytoplasm, nucleus, and nucleolus in HeLa cells, implying passive or semi-active translocation without a receptor. The proposed nuclear access is the foundation for all downstream DNA-binding claims.
Proposed direct DNA binding
Molecular modeling and fluorescence quenching suggest preferential binding to d(CCTGCC)2, d(CCAGC)2, and CNG/CAG-containing oligonucleotides. Binding specificity in vivo has not been independently validated.
Reactive oxygen species suppression
Reduces ROS accumulation in rat cerebellar granule cells, PC12 cells, and human neutrophils under ouabain, H2O2, or homocysteine stress in vitro.
Delayed ERK1/2 activation
Extends the lag phase of MAPK/ERK activation under oxidative stress in rat cell culture; proposed as part of the neuroprotective signaling story.
Antioxidant enzyme induction (SOD2, GPX1)
Raises SOD2 and GPX1 activity in hypoxia-sensitive rat brain toward levels observed in hypoxia-resistant rats.
Caspase-3 / p53 modulation
Reduces caspase-3 activity in aged rat brain after hypoxic hypoxia and alters p53-related apoptotic signaling. Reduced apoptotic clearance of damaged cells is a theoretical long-term safety concern not evaluated in any long-duration study.
PPARA / PPARG transcriptional binding (in silico)
Proposed binding motifs identified in PPARA and PPARG promoters through in silico scanning only, no functional ChIP or reporter-assay validation published.
TPH1 / serotonin synthesis
Increases serotonin expression in rat brain cortex cultures; one predicted TPH1 promoter binding site.
Every mechanistic claim above derives from the Khavinson research network (St. Petersburg Institute of Bioregulation and Gerontology and direct collaborators). There is no independent replication in Western labs of the proposed sequence-specific DNA-binding mechanism, and the idea that a naked, charged tripeptide efficiently crosses plasma and nuclear membranes to exert transcriptional effects is not a mainstream pharmacological model. Most of the downstream gene-regulation claims (PPARA, PPARG, TPH1 binding) come from in silico promoter scanning rather than functional ChIP or reporter assays. Treat the mechanism as "proposed by one research school" rather than "established."
Key studies
Independence warning: most research for this peptide originates from a single research group. Replication by independent groups is limited.
Pinealon Increases Cell Viability by Suppression of Free Radical Levels and Activating Proliferative Processes (2011)
Khavinson V.Kh., Lin'kova N.S., Tarnovskaia S.I., Umnov R.S., Elashkina E.V., Durnova A.O. · Rejuvenation Research 14(5):535–541
- Participants
- Rat cerebellar granule cells, human neutrophils, PC12 pheochromocytoma cells (all cell culture)
- Methodology
- Induced oxidative stress with ouabain, homocysteine, H2O2, or zymosan; measured ROS, propidium-iodide necrosis, and ERK1/2 phosphorylation timing with vs without Pinealon.
- Result
- Dose-dependent reduction of ROS and necrosis; delayed ERK1/2 activation.
Honest read
In vitro only. Single research group. No independent cell-biology replication in the 15 years since. ROS quenching in a dish is mechanistically plausible for any charged small molecule and is a low-bar assay. Relevance to human cognition is unestablished.
Pinealon protects the rat offspring from prenatal hyperhomocysteinemia (2012)
Arutjunyan A.V., Kozina L.S., Stvolinskiy S.L., Bulygina Y.V., Mashkina A.P., Khavinson V.Kh. · Int J Clin Exp Med 5(2):179–185
- Participants
- Pregnant Wistar rats loaded with methionine to induce hyperhomocysteinemia; 3 groups, 6 families each, 23 pups per behavioral arm
- Methodology
- 10 µg/kg i.p. Pinealon to pregnant dams; Morris water maze in 45-day-old pups; flow cytometry ROS/PI on cerebellar granule cells from 10-day-old pups.
- Result
- Pinealon-treated pups had normal body weight, better spatial navigation, fewer necrotic neurons, and lower ROS vs methionine-only pups. Plasma homocysteine unchanged.
Honest read
Small animal study with non-blinded outcome measurement and small sample (~23/arm for behavior, n=4–5 for chemistry). Affiliation: D.O. Ott Institute + Khavinson's own Institute of Bioregulation and Gerontology, not an independent group. Model is disease-specific (prenatal hyperhomocysteinemia), not a generalizable aging model. The Int J Clin Exp Med is a low-impact, frequently-criticized venue.
Penetration of short fluorescence-labeled peptides into the nucleus in HeLa cells and specific interaction of the peptides with deoxyribooligonucleotides and DNA in vitro (2011)
Fedoreyeva L.I., Kireev I.I., Khavinson V.Kh., Vanyushin B.F. · Biochemistry (Moscow) 76(11):1210–1219
- Participants
- HeLa cell cultures; in vitro FAM-labeled oligonucleotides for Stern-Volmer quenching
- Methodology
- FITC-labeled Pinealon, Epithalon, Testagen incubated with HeLa cells; fluorescence imaging of cytoplasm/nucleus/nucleolus; Stern-Volmer quenching with FAM-labeled oligonucleotides.
- Result
- All three peptides found in nuclei; Pinealon quenched CAG- and CNG-containing sequences preferentially.
Honest read
FITC-peptide localization is notoriously artifact-prone, fluorophore alone can drive cellular uptake, and fixation-induced redistribution is a known issue in the broader cell-penetrating-peptide literature (see Wikipedia/CPP). The study does not address whether unlabeled EDR penetrates comparably, nor whether the binding is strong/specific enough to matter at physiological concentrations. This is the single cited source for most downstream "direct DNA regulator" claims.
Neuroprotective Effects of Tripeptides EDR and KED in an In Vivo 5xFAD Model of Alzheimer's Disease (2021)
Khavinson V., Ilina A., Kraskovskaya N., Linkova N., Kolchina N., Mironova E., Erofeev A., Bezprozvanny I. · Pharmaceuticals 14(6):515
- Participants
- 5xFAD-M transgenic mice (Alzheimer's model)
- Methodology
- EDR and KED peptides administered IP; dendritic spine morphology quantified.
- Result
- Both peptides prevented loss of mushroom-shaped dendritic spines.
Honest read
Same research group; MDPI's Pharmaceuticals has a more variable review standard than top neuroscience journals. Dendritic spine preservation is a surrogate endpoint, not cognitive function. No Western replication.
Research timeline
- 2007
Khavinson group files Russian and European patents describing short peptides stimulating CNS neuron regeneration, including EDR/Pinealon (EP 2024388 / WO 2007/139431).
- 2008
Kozina et al., Doklady Biological Sciences 418:419, first reports of in vivo antihypoxic effects of short peptides including Pinealon in rats.
- 2011
Fedoreyeva et al. show FITC-labeled Pinealon penetrates HeLa cell nuclei and binds specific oligonucleotides. Foundational mechanistic paper.
- 2011
Khavinson et al., Rejuvenation Research, foundational cell-viability / ROS study in rat cerebellar granule cells, PC12, and human neutrophils.
- 2012
Arutjunyan et al., Int J Clin Exp Med, prenatal hyperhomocysteinemia rat pup behavioral study.
- 2012
Bashkireva & Artamonova, open-label observational study; Pinealon combined with Vesugen in 150 truck drivers, outcomes confounded by the combination and lack of controls.
- 2013
Umnov, Linkova, Khavinson TBI/cerebrasthenia observational report (n=72), open-label, no placebo, authored by the same institute that markets the product.
- 2014
Mendzheritskii et al., Adv Gerontol, hypoxic hypoxia in aged rats; caspase-3 modulation reported.
- 2015
Trofimova et al. polymorbidity/organic brain syndrome case series, COUNTERSIGNAL: prooxidant activity and CD34+ hematopoietic suppression observed with Pinealon.
- 2017
Kraskovskaya et al., dendritic spine preservation in 5xFAD Alzheimer mouse model.
- 2019
Georgievna et al., 2-macaque preliminary report in a Moscow University anthropology bulletin (not well-indexed in Western databases).
- 2020
Khavinson et al. mechanistic review in Molecules, most-cited recent synthesis.
- 2021
Khavinson et al., Pharmaceuticals 14:515, 5xFAD Alzheimer's mouse neuroprotection with EDR and KED tripeptides.
- 2024
Vladimir Khavinson dies. Research program continues under collaborators (Linkova, Trofimova, Popugaeva, Kraskovskaya); future trajectory and independence of the Pinealon literature is uncertain.
- 2026
ClearBatch verification pass (April 2026): no registered preclinical-to-clinical development program identified for Pinealon in public trial registries, and no FDA 503A nomination has ever been submitted.
What we don't know
- Pharmacokinetics, no published PK data for EDR in any in vivo model. Oral bioavailability, plasma half-life, brain penetration, and metabolism of intact EDR vs hydrolysis to free amino acids are all uncharacterized.
- Whether oral EDR survives the gut, tripeptides are cleaved by brush-border peptidases, and there is no evidence that orally-administered Pinealon reaches the brain intact at physiologically meaningful concentrations in any studied organism.
- Specificity of DNA binding in vivo, in-silico promoter-motif matches (CCTGCC, CCAGC) are extremely short and occur many thousands of times across the genome; evidence of genuine functional selectivity is absent.
- Efficacy evidence for any claimed indication is limited to animal and in vitro studies with no independent replication outside the Khavinson network.
- Dose-response relationships, the doses used in preclinical studies have not been validated or contextualized by independent researchers.
- Long-term safety, no studies with formal adverse-event tracking beyond short observation windows.
- Interactions with other compounds, not formally studied in any model.
- Reproductive and developmental signals are limited to the rat prenatal hyperhomocysteinemia model; no independent follow-up.
- Purity and identity of commercial material, whether vendor-sold Pinealon is actually the intended L-Glu-L-Asp-L-Arg sequence rather than diastereomers, cyclic products, or truncation products is rarely independently verified.
- The FDA PCAC review of Epitalon (Khavinson-family sibling peptide) scheduled for February 2027 may set precedent for how the FDA characterizes short Khavinson peptide bioregulators generally.
Stability & handling
- Lyophilized shelf life
- Typically labeled 2–3 years at −20°C sealed and desiccated; 0–4°C acceptable for weeks
- Lyophilized storage
- Freeze at −20°C or below, sealed and desiccated; protect from light and moisture
- Reconstitution diluents
- Sterile physiological saline or bacteriostatic water (research use), Sterile water or PBS (cell culture)
- Reconstituted (refrigerated)
- Short (days to ~2 weeks) refrigerated at 2–8°C
- Reconstituted (room temp)
- Not recommended for extended periods, stability not characterized
- OK to refreeze
- No
- Light sensitive
- Yes, protect from light
EDR has a small MW (~418) and is prone to hygroscopic mass gain; keep desiccated. Do not refreeze thawed reconstituted solution, repeated freeze/thaw cycles increase hydrolysis and adsorption loss. If long-term frozen storage is needed, divide reconstituted solution into single-use aliquots at reconstitution time and thaw each aliquot only once. No peer-reviewed stability characterization (e.g., forced degradation studies with mass spec) of Pinealon specifically has been identified in the primary literature; the values above are vendor-derived.
Frequently asked questions
Is it banned by WADA?
It is not named on the 2026 Prohibited List but falls under the catch-all category S0 (Non-Approved Substances), which captures any substance not authorized by a regulatory authority. The S0 category is the default for unapproved peptides that lack an explicit listing.
Pinealon vs Epitalon, what's the difference?
Both come from the Khavinson program. Epitalon (Ala-Glu-Asp-Gly, AEDG) is a tetrapeptide associated with claimed pineal/telomerase effects and has a larger (still mostly single-group) literature. Pinealon (EDR) is a tripeptide positioned as the neuroprotective cousin. They are NOT the same peptide and should not be conflated.
Why does so much of the marketing copy sound impressive?
Because the Khavinson group published a very large number of papers over four decades, mostly in Russian journals and mostly in-house. Vendors quote the sheer volume and use phrases from those papers. Volume of publication is not the same as independent replication or regulatory acceptance, a distinction that is easy to lose on vendor pages.
Is it the same as "Cortexin"?
No. Cortexin is the original animal-derived polypeptide mixture from bovine/porcine cerebral cortex, a registered product in Russia/CIS countries. Pinealon is a single synthetic tripeptide (EDR) that was identified as a fragment of Cortexin and is marketed separately. Conflating them is a common marketing-copy error.
What should I look for on a Pinealon COA?
A Pinealon COA should report four things, separately: (1) peptide content (%) distinct from HPLC purity (%), stated vial masses often represent salt weight, not peptide content; (2) counterion identity (acetate vs TFA) and % by mass, residual TFA above ~0.5% can be cytotoxic; (3) ESI-MS confirmation of the 418-Da molecular ion; (4) chiral/stereochemistry verification (chiral HPLC or NMR), charged tripeptides with Glu and Asp side chains are prone to aspartimide formation yielding β-Asp and D-Asp impurities. Endotoxin (LAL) testing is also relevant for any injectable-intended peptide. A COA that reports only "HPLC purity ≥98%" without the above has not actually demonstrated what is in the vial. ClearBatch's vendor pages show which of these signals are published per batch.
Last researched: Apr 19, 2026
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