Pinealon Research, Specifications & Scientific Information

Introduction

Pinealon is three amino acids: glutamate, aspartate, arginine. It comes from the same St Petersburg programme as Epitalon and rests on the same premise — that a short synthetic sequence can reproduce the regulatory activity of the tissue extract its composition was derived from — and it carries the same proposed mechanism, direct interaction with DNA rather than binding to a receptor.

What distinguishes it from most of that series is that one piece of its mechanistic case has been examined outside the programme. A 2019 study from a physics department at St Petersburg State University used spectroscopy, nuclear magnetic resonance, viscosimetry and molecular dynamics to look at whether the tripeptide interacts with DNA at all, and reported that it can partly penetrate the major groove and contact guanine base atoms, with magnesium ions promoting the interaction ^[3]. That is a physical result about a molecular interaction, not a biological result about an effect, and the distinction runs through this whole page.

The biological literature is thinner and more concentrated. Most of it is cell culture. Some is rodent work in Russian-language gerontology journals. The human record is one uncontrolled report in thirty-two people, which contains findings pointing in both directions.

What Is Pinealon?

Pinealon is the synthetic tripeptide Glu-Asp-Arg, written EDR in single-letter code, with free N- and C-termini and no modification. PubChem records it as compound identifier 10273502 under CAS registry number 175175-23-2.

It belongs to the series of short peptides developed by Vladimir Khavinson's group and marketed as peptide bioregulators. Each member of the series was designed from the amino-acid composition of a tissue-specific polypeptide extract, on the premise that a short sequence accounts for the activity of the complex it came from. Pinealon is presented within that scheme as the short peptide associated with brain and pineal tissue, which is where its name comes from.

Its regulatory position is worth stating plainly. It has not been approved by the U.S. Food and Drug Administration for any indication; no marketing application for it is on record in the United States; and no study of it is registered on ClinicalTrials.gov. In the Russian Federation it is sold as a non-pharmaceutical peptide preparation, which is not the same status as the registered medicines that some other compounds in this library hold there.

Pinealon Specifications

The formula and mass are PubChem's record for compound identifier 10273502, which corresponds to the unmodified free tripeptide with free N- and C-termini; the same record notes an acetate salt form, and material supplied as a reagent is commonly an acetate. CAS registry number 175175-23-2 is recorded against it. No UNII code resolves for the substance in the FDA/NCATS Global Substance Registration System, so that field is published as unknown rather than estimated. A mass measured on salt-form material will not equal the free-peptide figure above, and a purity statement that does not identify the counter-ion and the water content is incomplete.

Values that a public register does not carry are shown as not publicly characterised rather than estimated. Identifiers are reference values; the certificate of analysis supplied with a laboratory order is the record for a given lot.

How Does Pinealon Work?

No receptor has been proposed, and none has been sought successfully. The mechanism put forward by the originating group is that short regulatory peptides of this class enter cells, reach the nucleus, and interact directly with nucleic acids and with chromatin proteins, thereby influencing which genes are transcribed ^{[2, 8]}.

The case for that proposal has three parts, and they are of unequal strength.

That the peptide reaches the nucleus rests on fluorescence microscopy of labelled peptide in HeLa cells, where marked signal was observed in cytoplasm, nucleus and nucleolus ^[2]. A fluorescein label on a 418-dalton peptide is a substantial structural addition, and what is tracked is the conjugate.

That the peptide binds DNA with sequence preference rests on fluorescence-quenching measurements against labelled deoxyribooligonucleotides, from which the authors report that this tripeptide, along with Epitalon and bronchogen, binds preferentially to sequences containing the CNG motif, and that binding discriminates cytosine methylation status ^[2]. This is the most consequential claim in the programme, and it is the one that most needs independent replication.

That an interaction with DNA is physically real is the part that has been examined independently, and the answer was a qualified yes: partial penetration into the major groove, contacts at the N7 and O6 positions of guanine, and a dependence on divalent cations that screen the phosphate backbone ^[3]. Note what that study is and is not. It establishes that the molecule and the polymer interact under defined conditions. It says nothing about whether such binding occurs at physiological concentrations inside a cell, or what would follow if it did.

A separate strand of the mechanistic account is not about DNA at all: restriction of reactive oxygen species accumulation, reported across three different cell types ^[1]. The authors of that paper argue that the two strands are distinguishable, on the grounds that the antioxidant effect saturates at lower concentrations while the cell-cycle effect continues at higher ones.

No pharmacokinetic data of any kind are published for this tripeptide in any species. How a 418-dalton, highly polar, charged molecule reaches a cell nucleus in an intact organism is not addressed in the accessible literature.

Pinealon Mechanism of Action

In vitro research

Reactive oxygen species and cell viability. In cerebellar granule cells, neutrophils and PC12 pheochromocytoma cells under oxidative stress induced by receptor-dependent and receptor-independent stimuli, the tripeptide restricted reactive oxygen species accumulation in a concentration-dependent manner and reduced necrotic cell death measured by propidium iodide staining. The protective effect was accompanied by a delayed time course of ERK 1/2 activation and by modification of the cell cycle ^[1].

Nuclear localisation and nucleic-acid binding. Fluorescein-labelled peptide was observed in the cytoplasm, nucleus and nucleolus of HeLa cells. Stern-Volmer constants for quenching of labelled deoxyribooligonucleotides differed between peptides according to their primary structure, which the authors interpret as sequence-specific interaction; preferential binding to CNG-containing and CAG-containing sequences is reported for this tripeptide ^[2].

Physical characterisation of the DNA interaction. Spectral methods, nuclear magnetic resonance, viscosimetry and molecular dynamics indicated partial penetration into the major groove with effects on guanine N7 and O6 atoms, promoted by magnesium ions screening the DNA phosphate charge ^[3]. This is the only study on this compound located from a group with no connection to the originating programme.

Serotonin expression in cortical cultures. In ageing brain cortex cell cultures, the tripeptide was reported to stimulate serotonin expression, with molecular docking offered as the mechanistic account: a CCTGCC sequence in the tryptophan hydroxylase gene described as complementary to the peptide ^[4]. Docking is a computational prediction, and the paper presents it as one.

Induced neurons from elderly donors. In a model based on transdifferentiating dermal fibroblasts from elderly donors into induced cortical neurons, this tripeptide and two others increased dendritic arborisation — both the number of primary processes and total dendrite length. The tripeptides did not change mitochondrial or lysosomal activity or p16 protein levels; this one specifically reduced oxidative DNA damage ^[9]. The negative findings in that paper are as informative as the positive ones, and the authors report both.

Findings in this section were obtained in cell culture, in cell-free systems and by computation. Nothing in them establishes anything about intact animals or about humans.

What Is Pinealon Being Researched For?

• Peptide–DNA interaction as a proposed epigenetic mechanism — the central claim of the bioregulator programme, examined here in labelled-oligonucleotide binding ^[2] and in physical characterisation of the interaction ^[3].
• Neuroprotection under oxidative stress — reactive oxygen species restriction and necrotic death in three cell types ^[1], and oxidative DNA damage in induced neurons from elderly donors ^[9].
• Rodent models of prenatal and age-related stress — offspring of hyperhomocysteinaemic dams ^[5] and 18-month-old rats under hypobaric hypoxia and mild hypothermia ^[6].
• Serotonin and monoamine regulation — expression in cortical cultures ^[4] and mediator accumulation in aged rat brain ^[6].
• Alzheimer's disease pathogenesis, as a review-level hypothesis — a 2020 review from the originating group assembles the reported findings into a proposed pathway involving MAPK/ERK signalling, caspase-3 and p53, SOD2 and GPX1, and the PPARA and PPARG transcription factors ^[8]. That paper is a synthesis of existing reports, not new evidence.

None of that research is research into, or evidence about, research-grade material supplied for laboratory use.

Human Research on Pinealon

Human clinical research

Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.

There is one indexed human report on this tripeptide.

Biological-age indices in older adults, 2015

Design. Thirty-two people — 18 men and 12 women, aged 41 to 83 — with chronic polymorbidity and organic brain syndrome of the central nervous system in remission, given the tripeptide or the related tripeptide vesugen, with cellular and metabolic indices of biological age as the measured outcomes. Published in Russian in Advances in Gerontology ^[7].

Result as reported. Both preparations were described as having a significant anabolic effect and as slowing the rate of ageing by biological-age indicators, with vesugen showing the more pronounced effect of the two. Neither preparation affected the degree of chromatin condensation, which the authors offer as evidence of safety at the nuclear genetic level ^[7].

Findings pointing the other way. The same report describes prooxidant activity detected by chemiluminescence, and a decrease in circulating CD34-positive haematopoietic polypotent cells that the authors characterise as significant inhibition of haemopoiesis ^[7]. A geroprotective claim and a marrow-suppression signal in the same thirty-two people is a combination that should be read carefully rather than filtered.

Limitations. Thirty-two participants, no control group, no randomisation, no blinding, and composite biological-age indices rather than clinical endpoints. Two different peptides were administered within one small sample. The paper is indexed with an English abstract and is otherwise in Russian. Nothing in it is confirmatory, and the authors' own recommendation is framed as a suggestion for geriatric practice rather than as a demonstrated result.

That is the whole of the human record for this compound.

Preclinical Research on Pinealon

Animal research

Rat offspring under prenatal hyperhomocysteinaemia

Design. Pregnant rats were made hyperhomocysteinaemic by dietary methionine loading. The tripeptide was administered to the dams, and the offspring were assessed for cognitive function and for the oxidative resistance of isolated cerebellar neurons ^[5].

Result as reported. Offspring spatial orientation and learning ability were significantly improved, and reactive oxygen species accumulation and the number of necrotic cells among isolated cerebellar neurons were reduced ^[5].

Limitations. The indexed abstract reports no group sizes, no numerical results and no statistical detail. The journal is not one in which this programme's work is routinely scrutinised, and the study's own framing is that it confirms the group's earlier in vitro findings — which is the weakest form of confirmation, since the same hypothesis, the same laboratory and the same compound are on both sides.

Aged rats under hypobaric hypoxia and hypothermia

Design. Eighteen-month-old rats in two stress models — acute hypobaric hypoxia and mild hypothermia — given the tripeptide or the polypeptide preparation cortexin, with behavioural and neurochemical measures ^[6].

Result as reported. Cortexin had a more pronounced effect than the tripeptide on free-radical processes and on caspase-3 activity in brain. Both preparations promoted accumulation of adrenergic mediators in the hypoxia model and of serotonin in the cerebral cortex in the hypothermia model, which the authors suggest may underlie geroprotective effects ^[6].

Limitations. A Russian-language report with an abstract but no accessible numerical results. The comparator is a porcine-brain polypeptide complex rather than a placebo, and on the measures reported the tripeptide performed less well than that comparator.

Findings described in this section were observed in rats. Nothing in them establishes anything about humans.

Current Research Status

Status as of September 22, 2026. This block is rendered from maintained fields, not from prose, so it cannot go stale in one place and stay current in another.

Pinealon vs Related Compounds

Within the bioregulator series

Epitalon (Ala-Glu-Asp-Gly) is the best known member and has the larger literature, including the telomerase work in cultured fibroblasts. The two peptides were compared directly in the nuclear-penetration study, where both entered HeLa cell nuclei and both bound preferentially to CNG-containing sequences ^[2]. They share a programme, a premise and a proposed mechanism; they do not share results.

Against thymic bioregulators

Thymalin is the thymic preparation from the same programme and is a polypeptide complex rather than a defined short peptide — a difference in kind, not in degree.

Vesugen, the comparator in the human report

The one human study administered both this tripeptide and vesugen, and reported the more pronounced effect for vesugen ^[7]. A result generated in a sample of thirty-two people with no control arm does not rank two compounds against each other, and nothing here should be read as doing so.

Cortexin and cerebrolysin

The Russian rodent work sets this tripeptide against cortexin, a porcine brain polypeptide complex closely comparable to Cerebrolysin ^[6]. Those are undefined mixtures with their own evidence base; a short synthetic tripeptide is a different kind of substance and its results do not transfer to them, or theirs to it.

No comparison of effect between these compounds is made on this page.

Chemical & Molecular Characteristics

Pinealon is an unmodified three-residue peptide, and at 418 daltons it is among the smallest molecules in this library. Its chemistry is dominated by an unusual charge arrangement.

Two acids and one strong base, in that order. Glutamate at position 1 and aspartate at position 2 carry side-chain carboxylates; arginine at position 3 carries a guanidinium group that remains protonated across the entire physiological pH range, and the C-terminal carboxylate sits beside it. The molecule is therefore zwitterionic with charge separated along a very short backbone — three negative centres against two positive ones at neutral pH. That arrangement is directly relevant to the proposed mechanism: the guanidinium is the plausible contact point for DNA phosphate, and the carboxylates are what magnesium screening was reported to overcome ^[3].

No aromatic residue, so no ultraviolet handle. There is no tryptophan, tyrosine or phenylalanine, and therefore essentially no absorbance at 280 nm. Quantification must rely on peptide-bond absorbance near 214 nm, where buffers and solvents also absorb, or on a derivatisation method. This is a real analytical constraint and it applies to every lot of this material.

Reversed-phase retention is very poor. A 418-dalton peptide with this polarity is barely retained on conventional C18 columns and can elute close to the void volume, where it is hard to resolve from salts and from synthesis-related impurities. Purity "by HPLC" for a molecule of this kind is only as meaningful as the method behind it, and ion-pairing or hydrophilic-interaction chromatography is generally required to say anything useful.

Asp and Glu bring isomeric impurities that mass cannot detect. Both residues are susceptible to alpha/beta rearrangement chemistry, and the resulting isomers are identical in mass to the intended product. In a three-residue peptide the proportion of the molecule affected by a single such rearrangement is large. Mass spectrometry confirms composition; it does not confirm that the residues are joined in the intended way through the intended bonds.

Salt form. The PubChem record notes an acetate form and commercial material is commonly supplied as an acetate. A measured mass on salt-form material will not match the free-peptide figure, and the difference is proportionally larger for a molecule this small than for a large peptide.

No UNII code resolves for this substance in the FDA/NCATS Global Substance Registration System, so that field is published as unknown rather than filled with a plausible value.

Frequently Asked Questions

Scientific References

1. Khavinson V, Ribakova Y, Kulebiakin K, et al.. Pinealon increases cell viability by suppression of free radical levels and activating proliferative processes Rejuvenation research; 2011. PMID 21978084 doi:10.1089/rej.2011.1172
2. Fedoreyeva LI, Kireev II, Khavinson VKh, et al.. Penetration of short fluorescence-labeled peptides into the nucleus in HeLa cells and in vitro specific interaction of the peptides with deoxyribooligonucleotides and DNA Biochemistry. Biokhimiia; 2011. PMID 22117547 doi:10.1134/S0006297911110022
3. Silanteva IA, Komolkin AV, Morozova EA, et al.. Role of Mono- and Divalent Ions in Peptide Glu-Asp-Arg-DNA Interaction The journal of physical chemistry. B; 2019. PMID 30762356 doi:10.1021/acs.jpcb.8b10359
4. Khavinson VKh, Lin'kova NS, Tarnovskaya SI, et al.. Short peptides stimulate serotonin expression in cells of brain cortex Bulletin of experimental biology and medicine; 2014. PMID 24909721 doi:10.1007/s10517-014-2496-y
5. Arutjunyan A, Kozina L, Stvolinskiy S, et al.. Pinealon protects the rat offspring from prenatal hyperhomocysteinemia International journal of clinical and experimental medicine; 2012. PMID 22567179
6. Mendzheritsky AM, Karantysh GV, Ryzhak GA, et al.. [Pinealon and Cortexin influence on behavior and neurochemical processes in 18-month aged rats within hypoxia and hypothermia] Advances in gerontology = Uspekhi gerontologii; 2015. PMID 28509493
7. Meshchaninov VN, Tkachenko EL, Zharkov SV, et al.. [EFFECT OF SYNTHETIC PEPTIDES ON AGING OF PATIENTS WITH CHRONIC POLYMORBIDITY AND ORGANIC BRAIN SYNDROME OF THE CENTRAL NERVOUS SYSTEM IN REMISSION] Advances in gerontology = Uspekhi gerontologii; 2015. PMID 26390612
8. Khavinson V, Linkova N, Kozhevnikova E, et al.. EDR Peptide: Possible Mechanism of Gene Expression and Protein Synthesis Regulation Involved in the Pathogenesis of Alzheimer's Disease Molecules (Basel, Switzerland); 2020. PMID 33396470 doi:10.3390/molecules26010159
9. Kraskovskaya N, Linkova N, Sakhenberg E, et al.. Short Peptides Protect Fibroblast-Derived Induced Neurons from Age-Related Changes International journal of molecular sciences; 2024. PMID 39518916 doi:10.3390/ijms252111363

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Research-Use Information

For in vitro research use only. This material is a laboratory reagent. It is not a drug, food, dietary supplement, or cosmetic and is not for human or veterinary use, including ingestion, injection, or any other administration. No information on this page describes or implies any effect in humans or animals. Sold only to researchers under our Terms of Sale.