Epitalon — identity, handling and published literature

Epitalon is a synthetic acidic tetrapeptide (Ala-Glu-Asp-Gly, AEDG), supplied as a lyophilised powder for laboratory use, and reported in the literature as a pineal-derived sequence.

Presentation and physical properties

Epitalon is a linear, unmodified tetrapeptide with a free N-terminal amine and a free C-terminal carboxyl. Three of its four residues carry a carboxyl group, making it strongly acidic and among the more hydrophilic peptides in common laboratory circulation. It is encountered both as the free base and as the acetate salt; the two are distinct substances for weighing purposes, and material of either form may also carry trifluoroacetate from purification.

A 2025 review noted that structural and physicochemical investigation of this peptide is sparse relative to the volume of biological work published on it, and that molecular dynamics work describes two intramolecular salt bridges which constrain its conformational freedom in aqueous solution [1].

Reconstitution arithmetic

Reconstitution is a division. The concentration of the resulting solution is the mass of peptide in the vial divided by the volume of diluent added:

C (mg/mL) = m (mg) ÷ V (mL)

The mass of peptide contained in any subsequent aliquot is the reciprocal operation, m = C × V. Both relationships are arithmetic and hold regardless of what the material is or what is being investigated. Note that the lyophilised solid contributes its own small volume on dissolution, so the final volume slightly exceeds the diluent volume added; for the milligram quantities involved this is normally below the resolution of the syringe used to add the diluent, but it is a systematic bias in the same direction every time.

Expressed in micrograms per millilitre, a 10 mg vial in 2 mL gives 5,000 µg/mL; the same vial in 3 mL gives approximately 3,333 µg/mL. The recurring decimal at 3 mL is worth carrying through a calculation rather than rounding early, because rounding at the concentration step propagates into every mass derived from it.

Two arithmetic cautions specific to this molecule. First, the label mass on a peptide vial is conventionally the mass of material dispensed, not the mass of peptide it contains; acetate or trifluoroacetate counterions and residual water can account for a substantial fraction of that mass, so the true peptide concentration is lower than the division suggests unless a net peptide content figure is available and applied. Second, epitalon’s molar mass of 390.35 g/mol is low for a peptide, so a given mass corresponds to a comparatively large molar quantity: 10 mg is approximately 25.6 µmol, and 1 mg/mL is approximately 2.56 mM.

Storage and stability

As a lyophilised solid held cold, dry and dark, the peptide is comparatively stable; in aqueous solution it is not. The general principle for short peptides is that the solid state is the storage state and solution is a working state with a finite life. The 2025 review states plainly that short peptides such as this one are typically unstable and degrade rapidly, and notes that stabilising modifications such as N-terminal acetylation or C-terminal amidation have not been evaluated for it [1].

Freeze–thaw cycling is a specific liability. Each cycle concentrates solutes at the advancing ice front and shifts pH as buffer components crystallise differentially, which drives the chemical routes below. Dividing a reconstituted stock into single-use aliquots at the point of preparation removes the problem entirely, whereas repeatedly returning one vial to the freezer does not.

Degradation routes specific to this sequence

Aspartimide formation at the Asp-Gly bond. This is the dominant chemical liability and it is a direct consequence of the sequence. The aspartyl side-chain carboxyl attacks the backbone nitrogen of the following residue to form a five-membered succinimide ring, with loss of water. Asp-Gly is the most aspartimide-prone dipeptide motif known, because glycine has no side chain to sterically hinder the cyclisation, and epitalon carries that motif at positions 3–4. Hydrolysis of the succinimide reopens the ring at either carbonyl, regenerating the original α-aspartyl peptide or producing the isoaspartyl (β-linked) isomer, typically in favour of the latter. The reaction is accelerated by neutral-to-alkaline pH and by elevated temperature, and it also opens a racemisation route at the aspartyl α-carbon via the planar succinimide intermediate.

The analytical significance is that the principal degradant is an isomer. Isoaspartyl epitalon has exactly the same molecular formula and exactly the same mass as epitalon, so it is invisible to any test that measures mass alone and requires chromatographic separation to detect.

Acid-catalysed backbone hydrolysis. Aspartyl peptide bonds are the most labile of the common residues to acid hydrolysis, so storage in acidic solution or lyophilisation from strongly acidic media favours cleavage adjacent to the aspartate.

Routes that do not apply. It is as useful to know which degradation pathways this sequence cannot take. Epitalon contains no asparagine or glutamine, so there is no deamidation route. It contains no cysteine, so there is no disulphide scrambling and no thiol oxidation. It contains no methionine, tryptophan or histidine, so the usual oxidative liabilities of peptide storage are largely absent and protection from oxygen is a lower priority than protection from water and from warm neutral pH. It has no N-terminal glutamine or glutamate, so it cannot cyclise to pyroglutamate — a point exploited analytically below.

Microbial growth in reconstituted aqueous solutions is a separate concern from chemical degradation and is not addressed by refrigeration alone. Solutions prepared in non-preserved water offer no barrier to microbial proliferation, and a peptide solution supporting microbial growth will also be subject to enzymatic proteolysis from that source.

Analytical identity

Reversed-phase HPLC

Epitalon is difficult to retain on standard C18 stationary phases. With no hydrophobic residue and three ionisable carboxyls, it elutes at or near the void volume under conventional gradient conditions, where it co-elutes with salts and other polar material and cannot be resolved from its impurities. This is not a defect of the sample; it is a mismatch of method to analyte, and a chromatogram showing a single sharp early peak with excellent apparent purity is the expected artefact of that mismatch rather than evidence of a clean product.

Workable approaches are ion-pairing with trifluoroacetic acid or a longer-chain alkyl sulphonate to increase retention; an aqueous-compatible or polar-embedded C18 that tolerates highly aqueous starting conditions without phase collapse; or hydrophilic interaction chromatography (HILIC), which plays to the analyte’s polarity rather than against it. Detection is by UV at 205–215 nm, where the amide bond absorbs. Detection at 280 nm returns nothing, because the molecule has no aromatic residue.

Mass spectrometry

Electrospray ionisation with tandem MS is the reference technique for identity. Vanhee and colleagues reported LC-MSⁿ as an appropriate method for identifying epitalon in pharmaceutical preparations, in a study that arose from the analysis of two illegal preparations seized in Belgium [2]. Because the peptide is strongly acidic with a single basic site, negative-mode ionisation is often more efficient than positive mode, which is the reverse of the usual peptide situation and a common reason for poor signal when a generic positive-mode peptide method is applied unchanged.

Sequence-informative fragments distinguish epitalon from its sequence isomers. Calculated singly charged b-ions are b2 (Ala-Glu) at 201.087 and b3 (Ala-Glu-Asp) at 316.114; calculated y-ions are y2 (Asp-Gly) at 191.066 and y3 (Glu-Asp-Gly) at 320.109. The y3 ion is the discriminating fragment against the transposed isomer Glu-Ala-Asp-Gly, which has an identical precursor mass and an identical b2 ion but a y3 of 262.103.

An orthogonal chemical test for that same isomer is available and was described in the Vanhee work: a sequence beginning with glutamate can cyclise to pyroglutamate on heating, with a characteristic loss of 18 Da, whereas epitalon’s N-terminal alanine cannot [1,2]. A heat-treated sample that develops the corresponding mass shift is not epitalon.

What area-percent purity does and does not measure

An area-percent figure from an HPLC trace is the proportion of the integrated detector response falling under the main peak. It is a statement about that chromatogram under those conditions, and its limits are considerable.

It does not measure counterion content. Acetate or trifluoroacetate does not absorb usefully at 210 nm and does not appear as a peak, yet it contributes real mass to what is weighed. It does not measure residual water, which in a hygroscopic lyophilisate can be a significant mass fraction. It does not measure residual solvents, endotoxin or elemental impurities. Consequently a material reported at 99% area purity may be materially less than 99% peptide by mass, and net peptide content — determined by amino acid analysis, quantitative NMR or nitrogen determination — is a different measurement answering a different question.

Two limitations bite particularly hard on this molecule. First, area percent is blind to anything that co-elutes, and for a peptide this poorly retained on reversed phase under generic conditions, a great deal co-elutes. Second, the principal expected degradant is the isoaspartyl isomer, which is identical in mass and closely similar in polarity; unless the method has been shown to separate it, the isomer is counted inside the main peak and inflates the reported purity by exactly the amount the analyst most wants to know about. There is no pharmacopoeial monograph for epitalon and no certified reference standard, so there is no external anchor against which a supplier’s method can be judged.

What the published literature investigated

The published record is substantial in count and narrow in origin; the qualification in Evidence gaps and limitations below applies to everything in this section and should be read alongside it.

In vitro

The founding observation in this literature is a 2003 report by Khavinson, Bondarev and Butyugov which described induction of telomerase activity and telomere elongation in cultured human somatic cells exposed to the peptide [4]. A follow-up from the same authors reported that cells so treated continued dividing beyond the point at which control cultures ceased [5]. These two short papers are the source of most subsequent secondary description of the compound.

A 2025 study from the Centre for Genome Engineering and Maintenance at Brunel University London examined telomere length across a panel of normal and cancer-derived human cell lines, including normal fibroblasts and mammary epithelial cells alongside breast and prostate cancer lines, and reported concentration-dependent telomere lengthening in culture [6]. The authors reported that the mechanism appeared to differ by cell type, with hTERT upregulation in normal cells and alternative lengthening of telomeres (ALT) activity in cancer lines. A correction to that paper was published subsequently [7]. This is, so far as the indexed record shows, the first substantial work on this compound from a group unconnected to its originators.

A 2019 study reported measurements of telomere length and mitotic index in phytohaemagglutinin-stimulated human blood lymphocytes exposed to the peptide [8]. Earlier work using fluorescence-labelled short peptides reported nuclear penetration in HeLa cells and interaction with deoxyribo-oligonucleotides and DNA in vitro, offering a proposed mechanism by which a tetrapeptide might act on transcription [9]. Subsequent reports have described gene expression and protein synthesis during neurogenesis in culture [10], measurements in fibroblast-derived induced neurons [11], and proliferative and inflammatory pathway markers in the THP-1 monocyte/macrophage line [12]. A 2025 study reported effects on wound closure in an in vitro model of diabetic retinopathy [13].

A point of provenance worth recording: the tetrapeptide was synthesised and named as a pineal peptide well before it was reported to have been detected in pineal tissue. Its identification within the polypeptide complex of the pineal gland was published in 2017 [3].

Invertebrate

Three papers published in 2000 reported lifespan and antioxidant measurements in Drosophila melanogaster [14,15,16]. These are the earliest organism-level reports in the series and, like the cell work, originate with the same group.

Rodent and other animal models

The rodent literature is the largest block and is dominated by tumour-incidence and lifespan endpoints in cancer-prone strains, published between 2002 and 2007 largely by Anisimov, Khavinson and colleagues.

In HER-2/neu transgenic mice, two 2002 reports described reduced incidence and size of spontaneous mammary adenocarcinomas in treated animals [17,18]. In rats given 1,2-dimethylhydrazine to induce colon carcinogenesis, a 2002 paper in Cancer Letters reported an inhibitory effect on tumour development [19], and a 2003 follow-up examined proliferative activity and apoptosis in colon tumours and mucosa [23]. A 2003 study in female Swiss-derived SHR mice reported measurements of ageing biomarkers, lifespan and spontaneous tumour incidence [20]. A 2006 study in female C3H/He mice examined spontaneous carcinogenesis [22], and a 2002 report described chromosome aberration frequency in senescence-accelerated mice [21]. A 2007 study in female rats reported lifespan and spontaneous tumour development under differing illumination regimes [24].

A separate strand concerns the pineal axis. A 2003 study by Djeridane and colleagues, including a French co-author group, examined melatonin secretion by the pineal gland of young and old rats [25], and a 2002 report described pineal secretion in stress-exposed rats [26]. Retinal endpoints were examined in Campbell rats of various ages in 2003 [27].

More recent animal-derived work sits outside the original group. A 2022 study reported measurements in mouse oocytes subjected to post-ovulatory ageing in vitro [28], and a 2025 study from a Korean group reported maturation rates in bovine oocytes and development of post-thaw embryos [29]. In non-human primates, a 2005 study in Experimental Gerontology examined hormonal functions of the pineal gland and pancreas in aged monkeys using pineal peptide preparations [30].

Human

This subsection is short, and its brevity is the most important fact in this entry.

Exactly one record in PubMed carries the Clinical Trial publication type for this compound: a 2002 paper in Neuro Endocrinology Letters reporting outcomes in patients with degenerative retinal lesions [31]. The 2025 review describes this as having involved 162 patients [1]. The published abstract reports no randomisation, no blinding, no placebo group and no comparator, and the study originates with the group that developed the compound. It is a single-arm open observation.

Beyond that single record, work described as “human” in secondary sources is generally work on human cells rather than intervention in people. A 2004 paper reported chromatin measurements in lymphocytes obtained from elderly subjects [32], and a 2019 paper reported telomere length and mitotic index in stimulated human blood lymphocytes [8]; both are ex vivo observations on cells taken from donors, not studies in which anything was administered to a person.

The frequently cited long-term human work does not concern this compound. Korkushko and colleagues published a 15-year follow-up of elderly coronary patients randomised to receive a peptide geroprotector alongside standard therapy, reporting differences in mortality and in cardiovascular and metabolic measures over the follow-up period [33]. The substance administered in that study was epithalamin — a peptide extract prepared from bovine pineal tissue — and not the synthetic tetrapeptide described in this entry. A related 2007 Russian-language paper likewise reports on pineal gland peptide preparations in old monkeys and elderly people [34]. The distinction is set out further below.

Evidence gaps and limitations

This is the section that matters most for this compound, and nothing in the sections above should be read without it.

The evidence originates almost entirely from one research group

Essentially the whole literature traces to Vladimir Khavinson and the St Petersburg Institute of Bioregulation and Gerontology, together with a small number of long-standing collaborators — most prominently Vladimir Anisimov at the Petrov Institute of Oncology, also in St Petersburg. Khavinson appears as an author on the large majority of indexed records concerning this peptide, including the founding telomerase work, the Drosophila lifespan series, the rodent carcinogenesis series, the retinal work, and the single human study carrying a Clinical Trial designation. The compound was synthesised by that group, named by that group, tested by that group, and reviewed by that group.

This is not an allegation of misconduct. It is a structural statement about the evidence: a body of findings produced within a single laboratory tradition has not been subjected to the independent adversarial replication that is the mechanism by which scientific claims are ordinarily tested. Where every result comes from the people who expect it, the usual error-correcting process has not run.

Independent work is very recent and very limited. The 2025 study from Brunel University London [6] is the first substantial investigation from an unconnected group; it is in vitro only, it reports a mechanism partly different from the originating account, and it carries a published correction [7]. One in vitro paper from one independent laboratory does not constitute replication of a twenty-five-year literature.

Publication venue and language concentrate the same problem

A large proportion of the record appears in a small number of Russian journals and their English translations — principally Bulletin of Experimental Biology and Medicine (translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny) and Advances in Gerontology (Uspekhi Gerontologii). Several records are Russian-language originals for which only the abstract is available in English [34], so the methods cannot be scrutinised by a non-Russian-reading reader at all. Many of the individual papers are two to four pages long, which does not accommodate a full methods section, a power calculation, or the reporting of negative or ancillary findings.

Reporting standards in this body of work are, by contemporary expectation, weak. Blinding is rarely described. Randomisation is rarely described. Sample sizes are small and are not justified. Pre-registration does not feature. Protocols are not published. Data availability statements are absent. Effect sizes and confidence intervals are frequently not given.

There is no registered clinical trial

A search of ClinicalTrials.gov for epitalon and epithalon in August 2026 returned no registered studies. There is accordingly no publicly registered protocol, no pre-specified primary endpoint and no registered result for this compound anywhere in that registry.

No completed randomised controlled trial of the synthetic tetrapeptide has been published. No dose-ranging study has been published. No human pharmacokinetic characterisation has been published — absorption, distribution, metabolism, elimination and half-life are unestablished, which is a conspicuous gap for a four-residue peptide with no protecting modification, since such peptides are ordinarily expected to be cleared rapidly by ubiquitous peptidases. Notably, no human study has measured telomere length before and after administration under controlled conditions, despite telomere biology being the compound’s central claim to interest.

The single human interventional record is weak on its own terms

The 2002 retinal study [31] is uncontrolled, unblinded, unrandomised, single-arm, from the originating group, published in a journal that is not a general clinical outlet, and it has never been replicated by anyone. Its reported outcome is a proportion of participants judged to have responded, assessed without a comparator, in a setting where assessor expectation cannot be excluded. It would not today be accepted as evidence of effect in any regulatory or systematic-review context.

The most-cited human evidence is for a different substance

This point causes persistent confusion in secondary sources and should be stated flatly. Epithalamin and epitalon are not the same thing. Epithalamin is a peptide extract of bovine pineal tissue: a biological preparation of undefined and batch-variable composition containing many peptides. Epitalon is a single, chemically defined synthetic tetrapeptide. The long-term human follow-up data most often quoted in support of epitalon — including the fifteen-year mortality follow-up in elderly coronary patients [33] — were generated using epithalamin, not the tetrapeptide.

The conflation is embedded in reference infrastructure and therefore propagates easily: PubChem’s synonym list for the tetrapeptide includes “Epithalamin” and “Epithalamine”, which is chemically incorrect. Any source that cites long-term human outcome data for epitalon should be checked against the underlying paper to establish which substance was actually administered. In most cases it was the extract.

Safety data are largely absent

The 2025 review states explicitly that information on critical safety questions is missing, naming genotoxic activity, carcinogenic potential, and food–drug and drug–drug interactions, and concluding that additional short- and long-term toxicity studies would be essential before the substance could be considered as an active pharmaceutical ingredient [1]. There is no published formal toxicology package, no established no-observed-adverse-effect level, and no immunogenicity assessment. Absence of reported adverse effects in small, short, unblinded, uncontrolled studies is not evidence of safety; it is an absence of the observations that would detect a problem.

The literature contains almost no negative results

Across roughly 150 indexed records, null and contradictory findings from the originating group are close to nonexistent. A research programme spanning twenty-five years, multiple species and many endpoints that reports supportive results almost uniformly is displaying a pattern more consistent with selective publication than with an unusually well-chosen hypothesis. This does not establish that the findings are wrong; it establishes that the published record cannot be taken as a representative sample of the experiments performed.

Product identity in circulation is unverified

There is no pharmacopoeial monograph and no certified reference standard for this peptide, so no supplier’s analytical claim can be traced to an external authority. The circumstance that prompted the principal published analytical method was the seizure of illegal pharmaceutical preparations containing the peptide [2]. Material offered commercially is not subject to any regulatory quality regime, and the analytical limitations described above — poor reversed-phase retention, no aromatic chromophore, and a mass-identical principal degradant — mean that routine purity documentation is unusually poor at detecting the problems most likely to be present.

Regulatory and standards position

United Kingdom

Epitalon holds no UK marketing authorisation and is not an authorised medicinal product. It is not listed under the Misuse of Drugs Act 1971 or the Misuse of Drugs Regulations 2001, and is not a controlled drug. It is supplied lawfully as a laboratory research chemical.

Its status is nonetheless claim-dependent rather than fixed. Under the Human Medicines Regulations 2012 and the MHRA’s Guidance Note 8, a substance presented as having properties for treating or preventing disease is a medicinal product by presentation regardless of its pharmacology — the principle established in Ter Voort (C-219/91). A supplier or publisher who attaches a therapeutic claim to this peptide converts it, in law, into an unauthorised medicinal product and commits an offence in placing it on the market. The compound’s regulatory position therefore depends on how it is described, not only on what it is.

European Union

No EMA marketing authorisation and no national authorisation in any member state. It is not recognised as an established active pharmaceutical ingredient, and no European Pharmacopoeia monograph exists. The Belgian medicines agency work that produced the principal published analytical method [2] arose in an enforcement context, following the identification of the peptide in illegal pharmaceutical preparations.

United States

Epitalon is not an FDA-approved drug and no approved product contains it. FDA has treated it as a bulk drug substance nominated for use in compounding under section 503A of the Federal Food, Drug and Cosmetic Act, in the category of substances raising characterisation and safety concerns. At its meeting of 23–24 July 2026, FDA’s Pharmacy Compounding Advisory Committee considered epitalon (free base) and epitalon acetate for inclusion on the 503A Bulks List and, according to contemporaneous trade reporting, voted to recommend inclusion alongside five other peptides. Advisory committee votes are recommendations and are not binding on FDA; formal action would be required before the substance could lawfully be used in compounding, and as at August 2026 no such action has been recorded. The substance remains unapproved.

FDA’s preferred spelling is “epitalon” while most of the scientific literature uses “epithalon”, a divergence that is itself a symptom of the compound’s weak standardisation.

Anti-doping

Epitalon is not named anywhere on the WADA Prohibited List, in any class. It is not a peptide hormone, growth factor or related substance within the meaning of section S2, and it does not correspond to any other named class.

It does, however, fall within the scope of section S0, Non-Approved Substances, which prohibits at all times any pharmacological substance not addressed by another section of the List and with no current approval by any governmental regulatory health authority for human therapeutic use. Epitalon meets that description in every major jurisdiction. Substances captured by S0 are prohibited both in and out of competition. Any athlete subject to anti-doping rules should confirm status directly with their national anti-doping organisation or via Global DRO rather than relying on the absence of the compound’s name from the List.

Standards

No monograph exists in the British Pharmacopoeia, European Pharmacopoeia, United States Pharmacopeia or Japanese Pharmacopoeia. No certified reference material is available from a national metrology institute. There is consequently no authoritative specification against which a batch can be assessed, and no established compendial method for assay or related substances.

Laboratory handling and safety

The compound should be handled as a biologically active substance of incompletely characterised toxicology. The absence of published toxicity data is a reason for greater caution in handling, not less: the hazard profile is unknown rather than established as low, and no occupational exposure limit exists.

Personal protective equipment. Nitrile gloves, safety spectacles and a laboratory coat as a minimum. The lyophilised solid is low-density and readily becomes airborne when a vial is opened or a cake is disturbed, so weighing and any operation on the dry solid should be carried out in a fume hood, powder-weighing enclosure or containment balance to control inhalation exposure. Allow refrigerated vials to reach room temperature before opening, both to limit condensation into a hygroscopic solid and to reduce the pressure differential that scatters powder on opening.

Reconstitution. Add diluent slowly down the vial wall rather than directly onto the cake, and dissolve by gentle inversion or swirling. Vigorous vortexing and shaking generate an air–liquid interface that promotes surface denaturation and aggregation; for a short peptide this is less critical than for a protein but remains poor practice. Do not sonicate, which introduces localised heating.

Spills. Dry spills should be dampened before clearing, never brushed or swept, which re-aerosolises the powder. Wipe with a damp absorbent, working from the perimeter inwards. Liquid spills should be absorbed and the area wiped down; the peptide is water-soluble, so aqueous decontamination is effective. Dispose of contaminated absorbents as chemical waste.

Disposal. Treat as chemical waste in accordance with local arrangements and the Hazardous Waste Regulations where applicable. Do not dispose of peptide solutions to drain. Sharps used in reconstitution go to a designated sharps container.

Record-keeping. Record for each vial: supplier and batch or lot number, date received, the certificate of analysis as supplied and the analytical methods it names, storage location and temperature, date and time of reconstitution, identity and lot of the diluent, the mass and volume used and the calculated concentration, and the disposition of every aliquot. Where net peptide content is stated separately from gross mass, record both and record which was used in the concentration calculation. Retain the certificate of analysis alongside the experimental record; given the absence of any compendial standard for this substance, the supplier’s documentation is the only identity evidence that exists, and its limitations should be recorded with it rather than assumed away.

Independent verification of identity by LC-MS before use is advisable for any material intended to support a published result, and is proportionate given the documented circulation of this peptide outside regulated supply chains [2].

References

1. Araj SK, Brzezik J, Mądra-Gackowska K, Szeleszczuk Ł. Overview of Epitalon — Highly Bioactive Pineal Tetrapeptide with Promising Properties. International Journal of Molecular Sciences. 2025;26(6):2691. Review. PMID 40141333
2. Vanhee C, Moens G, Van Hoeck E, Deconinck E, De Beer JO. Identification of the small research tetra peptide Epitalon, assumed to be a potential treatment for cancer, old age and Retinitis Pigmentosa in two illegal pharmaceutical preparations. Drug Testing and Analysis. 2015;7(3):259–264. Analytical chemistry (LC-MSⁿ). PMID 25535022
3. Khavinson VK, Kopylov AT, Vaskovsky BV, Ryzhak GA, Lin’kova NS. Identification of Peptide AEDG in the Polypeptide Complex of the Pineal Gland. Bulletin of Experimental Biology and Medicine. 2017;164(1):41–43. Analytical, bovine pineal tissue. PMID 29124531
4. Khavinson VKh, Bondarev IE, Butyugov AA. Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells. Bulletin of Experimental Biology and Medicine. 2003;135(6):590–592. In vitro, human somatic cells. PMID 12937682
5. Khavinson VKh, Bondarev IE, Butyugov AA, Smirnova TD. Peptide promotes overcoming of the division limit in human somatic cell. Bulletin of Experimental Biology and Medicine. 2004;137(5):503–506. In vitro, human somatic cells. PMID 15455129
6. Al-Dulaimi S, Thomas R, Matta S, Roberts T. Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity. Biogerontology. 2025;26(5):178. In vitro, human normal and cancer cell lines. PMID 40908429
7. Al-Dulaimi S, Thomas R, Matta S, Roberts T. Correction: Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity. Biogerontology. 2025;27(1):1. Published erratum. PMID 41240216
8. Khavinson VK, Pendina AA, Efimova OA, Tikhonov AV, Koltsova AS, Krapivin MI, Petrovskaia-Kaminskaia AV, Petrova LI, Lin’kova NS, Baranov VS. Effect of Peptide AEDG on Telomere Length and Mitotic Index of PHA-Stimulated Human Blood Lymphocytes. Bulletin of Experimental Biology and Medicine. 2019;168(1):141–144. Ex vivo, human lymphocytes. PMID 31761987
9. Fedoreyeva LI, Kireev II, Khavinson VKh, Vanyushin BF. 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 (Moscow). 2011;76(11):1210–1219. In vitro, HeLa cells. PMID 22117547
10. Khavinson V, Diomede F, Mironova E, Linkova N, Trofimova S, Trubiani O, Caputi S, Sinjari B. AEDG Peptide (Epitalon) Stimulates Gene Expression and Protein Synthesis during Neurogenesis: Possible Epigenetic Mechanism. Molecules. 2020;25(3):609. In vitro, human stem cells. PMID 32019204
11. Kraskovskaya N, Linkova N, Sakhenberg E, Krieger D, Polyakova V, Medvedev D, Krasichkov A, Khotin M, Ryzhak G. Short Peptides Protect Fibroblast-Derived Induced Neurons from Age-Related Changes. International Journal of Molecular Sciences. 2024;25(21):11363. In vitro, human induced neurons. PMID 39518916
12. Avolio F, Martinotti S, Khavinson VK, Esposito JE, Giambuzzi G, Marino A, Mironova E, Pulcini R, Robuffo I, Bologna G, Simeone P, Lanuti P, Guarnieri S, Trofimova S, Procopio AD, Toniato E. Peptides Regulating Proliferative Activity and Inflammatory Pathways in the Monocyte/Macrophage THP-1 Cell Line. International Journal of Molecular Sciences. 2022;23(7). In vitro, THP-1 cell line. PMID 35408963
13. Gatta M, Dovizio M, Milillo C, Ruggieri AG, Sallese M, Antonucci I, Trofimov A, Khavinson V, Trofimova S, Bruno A, Ballerini P. The Antioxidant Tetrapeptide Epitalon Enhances Delayed Wound Healing in an in Vitro Model of Diabetic Retinopathy. Stem Cell Reviews and Reports. 2025;21(6):1822–1834. In vitro. PMID 40493162
14. Khavinson VK, Izmaylov DM, Obukhova LK, Malinin VV. Effect of epitalon on the lifespan increase in Drosophila melanogaster. Mechanisms of Ageing and Development. 2000;120(1–3):141–149. Invertebrate. PMID 11087911
15. Khavinson VKh, Izmaylov DM, Obukhova LK, Malinin VV. Effect of the Ala-Glu-Asp-Gly peptide on lifespan in Drosophila melanogaster. Doklady Biological Sciences. 2000;374:466–467. Invertebrate. PMID 11103316
16. Khavinson VK, Myl’nikov SV. Effect of pineal tetrapeptide on antioxidant defense in Drosophila melanogaster. Bulletin of Experimental Biology and Medicine. 2000;129(4):355–356. Invertebrate. PMID 10977918
17. Anisimov VN, Khavinson VKh, Alimova IN, Semchenko AV, Yashin AI. Epithalon decelerates aging and suppresses development of breast adenocarcinomas in transgenic her-2/neu mice. Bulletin of Experimental Biology and Medicine. 2002;134(2):187–190. Rodent, transgenic mice. PMID 12459848
18. Anisimov VN, Khavinson VK, Provinciali M, Alimova IN, Baturin DA, Popovich IG, Zabezhinski MA, Imyanitov EN, Mancini R, Franceschi C. Inhibitory effect of the peptide epitalon on the development of spontaneous mammary tumors in HER-2/neu transgenic mice. International Journal of Cancer. 2002;101(1):7–10. Rodent, transgenic mice. PMID 12209581
19. Anisimov VN, Khavinson VKh, Popovich IG, Zabezhinski MA. Inhibitory effect of peptide Epitalon on colon carcinogenesis induced by 1,2-dimethylhydrazine in rats. Cancer Letters. 2002;183(1):1–8. Rodent, induced carcinogenesis. PMID 12049808
20. Anisimov VN, Khavinson VKh, Popovich IG, Zabezhinski MA, Alimova IN, Rosenfeld SV, Zavarzina NY, Semenchenko AV, Yashin AI. Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice. Biogerontology. 2003;4(4):193–202. Rodent. PMID 14501183
21. Rosenfeld SV, Togo EF, Mikheev VS, Popovich IG, Khavinson VKh, Anisimov VN. Effect of epithalon on the incidence of chromosome aberrations in senescence-accelerated mice. Bulletin of Experimental Biology and Medicine. 2002;133(3):274–276. Rodent, SAM mice. PMID 12360351
22. Kossoy G, Anisimov VN, Ben-Hur H, Kossoy N, Zusman I. Effect of the synthetic pineal peptide epitalon on spontaneous carcinogenesis in female C3H/He mice. In Vivo. 2006;20(2):253–257. Rodent. PMID 16634527
23. Kossoy G, Zandbank J, Tendler E, Anisimov V, Khavinson V, Popovich I, Zabezhinski M, Zusman I, Ben-Hur H. Epitalon and colon carcinogenesis in rats: proliferative activity and apoptosis in colon tumors and mucosa. International Journal of Molecular Medicine. 2003;12(4):473–477. Rodent. PMID 12964022
24. Vinogradova IA, Bukalev AV, Zabezhinski MA, Semenchenko AV, Khavinson VKh, Anisimov VN. Effect of Ala-Glu-Asp-Gly peptide on life span and development of spontaneous tumors in female rats exposed to different illumination regimes. Bulletin of Experimental Biology and Medicine. 2007;144(6):825–830. Rodent. PMID 18856211
25. Djeridane Y, Khavinson VKh, Anisimov VN, Touitou Y. Effect of a synthetic pineal tetrapeptide (Ala-Glu-Asp-Gly) on melatonin secretion by the pineal gland of young and old rats. Journal of Endocrinological Investigation. 2003;26(3):211–215. Rodent. PMID 12809170
26. Sibarov DA, Kovalenko RI, Malinin VV, Khavinson VKh. Epitalon influences pineal secretion in stress-exposed rats in the daytime. Neuro Endocrinology Letters. 2002;23(5–6):452–454. Rodent. PMID 12500171
27. Khavinson VKh, Razumovsky MI, Trofimova SV, Razumovskaya AM. Retinoprotective effect of Epithalon in Campbell rats of various ages. Bulletin of Experimental Biology and Medicine. 2003;135(5):495–498. Rodent. PMID 12910293
28. Yue X, Liu SL, Guo JN, Meng TG, Zhang XR, et al. Epitalon protects against post-ovulatory aging-related damage of mouse oocytes in vitro. Aging (Albany NY). 2022;14(7):3191–3202. Rodent oocytes, in vitro. PMID 35413689
29. Ullah S, Haider Z, Perera CD, Lee SH, Idrees M, Park S, Kong IK. Epitalon-activated telomerase enhance bovine oocyte maturation rate and post-thawed embryo development. Life Sciences. 2025;362:123381. Bovine oocytes, in vitro. PMID 39788414
30. Goncharova ND, Vengerin AA, Khavinson VKh, Lapin BA. Pineal peptides restore the age-related disturbances in hormonal functions of the pineal gland and the pancreas. Experimental Gerontology. 2005;40(1–2):51–57. Non-human primate. PMID 15664732
31. Khavinson V, Razumovsky M, Trofimova S, Grigorian R, Razumovskaya A. Pineal-regulating tetrapeptide epitalon improves eye retina condition in retinitis pigmentosa. Neuro Endocrinology Letters. 2002;23(4):365–368. Human; indexed as Clinical Trial / Controlled Clinical Trial; no randomisation or blinding reported. PMID 12195242
32. Khavinson VKh, Lezhava TA, Malinin VV. Effects of short peptides on lymphocyte chromatin in senile subjects. Bulletin of Experimental Biology and Medicine. 2004;137(1):78–81. Ex vivo, human lymphocytes. PMID 15085253
33. Korkushko OV, Khavinson VKh, Shatilo VB, Antonyk-Sheglova IA. Peptide geroprotector from the pituitary gland inhibits rapid aging of elderly people: results of 15-year follow-up. Bulletin of Experimental Biology and Medicine. 2011;151(3):366–369. Human; the substance administered was epithalamin, a bovine pineal peptide extract, not the synthetic tetrapeptide. PMID 22451889
34. Korkushko OV, Lapin BA, Goncharova ND, Khavinson VKh, et al. [Normalizing effect of the pineal gland peptides on the daily melatonin rhythm in old monkeys and elderly people]. Advances in Gerontology. 2007;20(1):74–85. Russian language; non-human primate and human; pineal peptide preparations. PMID 17969590
35. Khavinson VKh. Peptides and Ageing. Neuro Endocrinology Letters. 2002;23(Suppl 3):11–144. Monograph-length review by the compound’s originator. PMID 12374906

Research use only

This entry is a record of published literature and physicochemical data, compiled for reference. It is not advice, and it is not a description of what this substance does.

Epitalon is a laboratory research chemical. It is not an authorised medicinal product in the United Kingdom, the European Union or the United States, and it is not approved for human or veterinary use in any jurisdiction. It is not for use in humans or animals, not for diagnostic or therapeutic use, and not for use in food.

Nothing in this entry states or implies that this compound treats, prevents, cures or improves any condition. Findings are reported as statements about the studies that produced them. No dosing, route, schedule or protocol is given anywhere in this entry, and none should be inferred from the reconstitution arithmetic, which concerns concentration only.

The compound described here is not sold by NovoVita. This entry exists because the reference library covers the published field rather than a product catalogue.