Preloaded Autoinjector | Epithalon | 3ml Pen | 15mg

The epithalon pen is a preloaded 3ml research autoinjector containing the tetrapeptide Ala-Glu-Asp-Gly in solution at 15/3 mg/ml, giving 15mg of peptide per device. The C-terminal Asp-Gly pair is the fastest succinimide-forming aspartyl sequence known, and its main degradation product weighs exactly what the parent weighs, so the fill date on this device carries more information than a mass-spectrometry identity check.

Specification Table

What Changes When Epithalon Ships in Solution?

Once Ala-Glu-Asp-Gly is dissolved, the aspartate at position 3 starts cyclising onto the backbone nitrogen of the glycine beside it, and the product, isoaspartyl AEDG, has the same formula and the same 390.35 g/mol mass as the intact peptide.

The mechanism is the aminosuccinyl route. The amide nitrogen of Gly4 attacks the side-chain carbonyl of Asp3, closing a five-membered succinimide ring and expelling water. Water then reopens the ring at either carbonyl: one opening regenerates the alpha-linked aspartate, the other gives beta-linked isoaspartate, in which the backbone now runs through the former side chain. The split is typically about 3:1 in favour of the isoaspartyl form, and the ring racemises at the alpha carbon, so some D-aspartate appears as well. Every one of those products is still C₁₄H₂₂N₄O₉.

Glycine is why this peptide ranks where it does. Stephenson and Clarke (1989) measured imide formation in Val-Tyr-Pro-X-Y-Ala hexapeptides at pH 7.4 and found that a glycine after aspartate or asparagine accelerated ring closure 6.5 to 17.6-fold relative to alanine, because glycine has no side chain to block the approach. Asparagine cyclised 13 to 36 times faster than aspartate in the same study, so Asp-Gly is the fastest aspartyl pair rather than the fastest pair outright. AEDG contains no asparagine, which is the one favourable fact in its sequence.

Formulation pH decides which product accumulates. Oliyai and Borchardt (1993) followed an Asp-Gly model hexapeptide across the pH range and found three regimes: below pH 3, direct hydrolysis of the Asp-Gly bond dominates, cutting off glycine and leaving Ala-Glu-Asp at about 333 Da; between pH 4 and 5, hydrolysis and isomerisation run in parallel; above pH 6, isomerisation is the only product. A near-neutral fill accumulates an invisible degradant. An acidic fill accumulates a visible one. Neither pH is on the product record.

Mass silence is the operational consequence. An LC-MS identity check reporting 390.1 is consistent with an entirely intact fill and with a fill in which a large fraction has isomerised. Separating the two needs a reversed-phase gradient shallow enough to resolve the isomer, or an enzymatic assay based on protein L-isoaspartyl methyltransferase, and neither is part of a routine certificate. Fill date, storage temperature and formulation pH are the three numbers from which the isoaspartate fraction could be estimated, and only the temperature is under the purchaser’s control, which is why the fill date counts for more on the epithalon pen than on most pens.

The remaining routes are minor. The free N-terminal alanine could close a diketopiperazine with Glu2, but Goolcharran and Borchardt (1998) found that reaction slow unless residue 2 is proline or glycine, and it is unmeasured for AEDG. There is no methionine, tryptophan, cysteine, histidine or tyrosine, so oxidation has nothing to attack and light has nothing to excite above about 220 nm. No approved product exists to borrow a formulation from, and Araj and colleagues (2025) state that physico-chemical investigations of the peptide “remain quite limited”: no study of epitalon solution stability exists, so every shelf-life statement rests on model-peptide kinetics.

What Is Epithalon?

Epithalon is the synthetic tetrapeptide Ala-Glu-Asp-Gly, designed by the Khavinson group in St Petersburg as a defined replacement for Epithalamin, a bovine pineal extract, and sold under the spellings Epitalon, Epithalon and Epithalone.

Four L-residues, a free amine at the alanine end, a free acid at the glycine end, no modification of any kind. Average molecular weight 390.35 g/mol, monoisotopic mass 390.14 Da, calculated XLogP3 of -5.5, modelled net charge about -2 at pH 7. No receptor has been identified; the group proposes nuclear entry and epigenetic regulation of about 98 genes, including Clock, Cry2, p16, p21 and TERT.

The extract and the tetrapeptide are not interchangeable, and the human cohort data belong to the extract. So the answer to what is epithalon, for this cartridge, is the four-residue molecule and nothing inherited from Epithalamin.

How Concentrated Is the Epithalon Pen?

At 15mg in 3 ml the concentration is 15/3 mg/ml, the molar concentration is 15 x 0.854 mM, and each 0.01 ml increment carries 15/300 mg of peptide, so a 10 mg fill delivers 33.3 ug per increment.

For a 10 mg fill: 3.333 mg/ml, divided by 390.35 g/mol and multiplied by 1000, is 8.54 mM or 8,539 uM. One 0.01 ml increment is 33.3 ug, or 85.4 nmol; ten increments (0.1 ml) deliver 333 ug.

Those figures sit far from the published assays. Sinjari and colleagues (2020) used 0.01 ug/ml, which is 25.6 nM, and the wider in-vitro range of 2 to 200 ng/ml is 5 to 512 nM. A 10 mg fill at 8.54 mM is about 334,000-fold above the Sinjari concentration. Anisimov’s mice received 10 ug/ml in saline, so the same fill is 333-fold more concentrated than the lifespan-study solution, and one 0.01 ml increment holds 33 times the 1.0 ug a single mouse received.

One number constrains 15. The only published solubility figure is 5 mg/ml for the trifluoroacetate salt in PBS at pH 7.2 (Cayman); nothing in plain water was found. A 15 mg fill in 3 ml sits exactly at that figure, and anything above it depends on an excipient system the record does not describe. The peptide calculator does the serial-dilution conversions.

Epithalon Pen vs Vial: What Does the Format Suit?

The epithalon pen suits repeated same-lot draws where the alternative is reconstituting a lyophilized vial each time, and it suits long storage after purchase poorly, because the succinimide clock runs from the fill line rather than from the first draw.

In the Epitalon 10mg lyophilized vial the Asp-Gly bond is quiet until diluent goes in, so a solution reconstituted on the morning of an experiment has an age known to the hour. The pen swaps that for a concentration fixed at manufacture and no diluent-volume, dissolution or transfer error, the trade the pen versus vial article works through in general terms.

For this molecule the trade tilts by application. Many equivalent draws over a few weeks, with the isoaspartate fraction taken as a constant background, favour the pen; a study running for months, or one needing a known isoaspartate fraction at the moment of use, favours a vial opened fresh. The preloaded autoinjector category page covers graduation resolution and cold-chain history; with a nasal spray also listed, the epithalon pen vs vial decision is a three-way one here.

What the Product Record Does Not State

Five things are absent from the epithalon pen product record: the salt form, the formulation pH, the excipient system, the fill date, and any measured isoaspartate content at release or over shelf life.

The salt form changes how much peptide a milligram holds. AEDG is sold as the acetate or the trifluoroacetate, and one TFA counterion adds 114 Da to a 390 Da peptide, so up to 22.6 percent of a weighed milligram could be counterion. Whether 15mg means net peptide or gross salt is a certificate question.

The pH decides which degradant forms, as set out above, and is not published. Nor is the excipient system, and for a peptide carrying a net charge of about -2 the buffer species and ionic strength both follow it into any assay. The fill date is the number from which the solution’s age, and so its expected isoaspartate fraction, would be estimated. Confirm against certificate of analysis.

Verifying the Epithalon Pen Before Use

Inspect the solution against a dark and then a white background before each draw: it should be clear and colourless with no particulate, and because AEDG has no aromatic residue, clarity is the only visual handle the device gives.

Let the cartridge reach room temperature before actuating, since a cold, more viscous solution delivers a different volume through a spring mechanism, and verify delivered volume once per device gravimetrically. What follows is specific to this peptide.

There is no absorbance at 280 nm. With no tryptophan or tyrosine, the peptide bond is the only chromophore and detection has to run at 210 to 220 nm, where excipients with carbonyl groups also absorb, so a UV concentration check needs a matched blank the record does not enable. Mass spectrometry sees glycine loss at about 333 Da and misses isoaspartyl AEDG, which sits on the parent at 390. Resolving it takes a shallow reversed-phase gradient run against a same-day reference reconstituted from a lyophilized vial, or a protein L-isoaspartyl methyltransferase assay. A device weeks into use, in an experiment whose result depends on epitalon solution stability, is where either measurement earns its cost.

Fibril checks rank low. Nothing reports aggregation of this tiny, anionic, hydrophilic molecule. The one scenario worth watching is a fill near the 5 mg/ml solubility figure cooled to 2°C, where precipitation would show as haze before it showed as a lower delivered mass.

What Does the Epithalon Literature Actually Report?

The synthetic tetrapeptide has one telomerase paper, two rodent lifespan studies, a handful of in-vitro gene-expression papers and no controlled human trial, and nearly all of it comes from one St Petersburg institute and its collaborators.

Khavinson, Bondarev and Butyugov (2003) reported that AEDG induced expression of the telomerase catalytic subunit, telomerase activity and telomere elongation in telomerase-negative human fetal fibroblasts. That paper is behind every telomere claim attached to the molecule and has not been independently replicated in the 23 years since.

Anisimov and colleagues (2003) gave female SHR mice 1.0 ug subcutaneously on five consecutive days each month from age 3 months, 54 per group. Mean lifespan did not change. Maximum lifespan rose 12.3 percent and the last 10 percent of survivors lived 13.3 percent longer (P < 0.01); leukaemia incidence was 6-fold lower and bone-marrow chromosome aberrations 17.1 percent lower. Vinogradova and colleagues (2008) gave male rats 0.1 ug subcutaneously five times a week for life under three lighting regimens and found no mean-lifespan gain and fewer spontaneous tumours. Khavinson (2000) reported extended lifespan in Drosophila.

The cell and tissue work adds mechanism without a receptor. Djeridane (2003) reported restored melatonin secretion in pineal explants from aged rats; Sinjari and colleagues (2020) reported 1.6 to 1.8-fold rises in nestin, GAP43, beta-tubulin III and doublecortin in human gingival mesenchymal stem cells at 0.01 ug/ml, with docking models placing the peptide on linker histones H1/3 and H1/6.

Human data belong to the extract. Khavinson and Morozov (2003) followed 266 people over 60 for 6 to 8 years after 2 to 3 years of Epithalamin and/or Thymalin and reported mortality 1.6 to 1.8-fold lower with the extract alone and 4.1-fold lower after six annual combined courses, in an open, non-randomised design. No randomised trial of synthetic AEDG was identified, and FDA’s 2026 reviewers called the human studies “short in duration, small in sample size, and insufficient to establish safety or effectiveness”. Unstudied: pharmacokinetics in any species, toxicology, independent replication of the telomerase result, and solution stability. The telomerase and telomere research article covers the fibroblast data in more detail.

Pinealon vs Epitalon: What Is the Difference?

Pinealon is the tripeptide Glu-Asp-Arg (EDR) and Epitalon is the tetrapeptide Ala-Glu-Asp-Gly (AEDG); both come from the Khavinson group, but only AEDG carries the telomerase and lifespan literature, and only AEDG has the fast Asp-Gly succinimide site.

EDR has a molecular weight of about 418.4 g/mol against 390.35, and its arginine brings the net charge near -1 at pH 7 where AEDG sits near -2. In EDR the aspartate is followed by arginine, whose side chain slows ring closure relative to glycine, so the same succinimide route exists but runs slower, which makes the aedg vs edr peptide contrast a stability contrast as well as a sequence one. The names mislead: Pinealon is marketed for brain-tissue research despite the pineal in its name, while Epitalon is the one designed from pineal extract. Most searches for pinealon vs epitalon are naming confusion; the difference between pinealon and epitalon in evidence terms is that AEDG has rodent lifespan and telomerase papers and EDR has neither. Neither peptide has a receptor, a pharmacokinetic study or a controlled human trial.

What Is the Safety and Regulatory Position of Epithalon?

No regulator has approved AEDG in any form: nothing appears in Drugs@FDA, the EMA register, PMDA, TGA or Health Canada, and the 24 July 2026 US advisory committee vote in its favour is a recommendation, not a rule.

FDA placed the peptide in Category 2 of the interim 503A bulk drug substances list on 29 September 2023 and removed it, effective 22 April 2026, pending advisory review. At the Pharmacy Compounding Advisory Committee meeting of 24 July 2026, under docket FDA-2025-N-6895 with insomnia as the nominated use, the committee voted 7 yes, 4 no and 1 abstention to recommend inclusion, against FDA’s own recommendation. No rulemaking has followed and the peptide is not on the 503A list. Russian status could not be verified, and the peptide was not found by name on the WADA Prohibited List, which should be confirmed against the current document.

Adverse findings are absent rather than reassuring. The rodent studies reported none, and FDA’s reviewers judged the safety database insufficient rather than identifying a harm. Telomerase activation is a theoretical oncology concern for any compound with the 2003 fibroblast result attached to it; the mouse and rat studies reported fewer tumours, not more, which is the only tumour data there is. No toxicology and no pharmacokinetics exist in any species.

What Do the Four Residues in the AEDG Peptide Contribute?

Two of the four side chains in the AEDG peptide carry a negative charge at neutral pH, and both come from acidic amino acids. Position 2 is glutamic acid, which contributes a three-carbon side chain ending in a carboxylate. Position 3 is aspartic acid, one carbon shorter, and that single missing carbon is the whole reason this molecule is unstable in water: the shorter arm can reach the backbone nitrogen next to it and close a ring, while the glutamic acid arm cannot reach comfortably and largely does not try.

Alanine at position 1 leaves a free amine at the N-terminus. Glycine at position 4 leaves a free acid at the C-terminus and, having no side chain of its own, gets out of the way of the aspartate beside it. So the sequence is short, doubly charged, wholly hydrophilic, and carries no aromatic ring anywhere along it. That last fact is why the solution is expected to look like water and why no absorbance check at 280 nm can confirm what is in the cartridge.

Why Is Epithalon Tied to the Pineal Gland and Melatonin?

The connection is historical rather than structural. Epithalamin, the starting point for this work, was an extract of bovine pineal gland prepared at the Institute of Bioregulation and Gerontology in St. Petersburg, and Vladimir Khavinson’s group synthesised AEDG as a defined four-residue stand-in for whatever in that extract was active. Nothing in the tetrapeptide’s chemistry points at that organ. The association is inherited from the tissue the extract came from.

That inheritance is why melatonin appears in almost every description of the compound. That gland is the body’s main site of melatonin production, so an extract from it was expected to act on the same system, and Khavinson and Morozov (2003) reported restored night-time rhythm in older subjects given the peptide. The measurement was made in a small unblinded cohort and has not been repeated by an independent group. Any statement about circadian regulation from this molecule rests on that single report.

The wider claim, that the peptide restores circadian rhythm or improves sleep quality, has the same problem in a sharper form. Sleep quality was not a measured endpoint in the published rodent work at all, and the human circadian rhythms data comes from the same laboratory that developed the compound. The 2025 FDA nomination named insomnia as the intended use, and FDA’s own reviewers described the supporting evidence as insufficient. Claims about hormonal balance are downstream of the same thin base.

What Do Telomere Length and Cellular Aging Claims Rest On?

One experiment. Khavinson, Bondarev and Butyugov (2003) added the peptide to human fetal fibroblasts in culture and reported telomerase induction with telomere length increasing past the point where the cells would normally have stopped dividing. That is the entire primary basis for every telomere maintenance claim attached to this compound, and it has not been independently replicated in the twenty-two years since.

The rodent work is separate and does not measure telomeres at all. Anisimov and colleagues (2003) and Vinogradova and colleagues (2008) followed mice and rats given the peptide across their lifespans and reported longer mean survival with fewer spontaneous tumors in the treated groups. Those are colony-level outcomes. Neither study reported cellular senescence markers, telomerase activity in tissue, or any measure of biological age other than how long the animals lived.

This matters for how the cellular aging language should be read. A compound that induces telomerase in a dish and a compound that extends rodent lifespan may be doing the same thing or entirely different things, and no published work connects the two results mechanistically. The anti-aging framing that surrounds the peptide runs ahead of that gap rather than through it. Nothing in the literature measures cellular health in a human given the compound.

What Side Effects Have Been Reported?

None, and that is a statement about the size of the record rather than about the compound. The rodent lifespan studies reported no treatment-related adverse effects. The small human reports from the St. Petersburg group reported none either. No study designed to find side effects has ever been run on this peptide, in any species, at any dose.

What that leaves unaddressed is worth naming. There is no toxicology package and no pharmacokinetic data. Injection site reactions, the most ordinary finding for any subcutaneous injection of a peptide preparation, have never been systematically recorded for AEDG, so their absence from the literature carries no information. The acetate or trifluoroacetate counter-ion in the fill is unstated, and trifluoroacetate has its own local irritancy profile in cell work.

No FDA-approved product contains this peptide. The FDA-approved status of a molecule is what generates a label, and a label is what collects adverse effects at scale over years. Without one, the safety record here is a handful of small studies from a single research group, which is not a safety record.

Is This Peptide Therapy?

No. Peptide therapy is a term used by clinics offering peptide preparations to patients, and it describes a service rather than a class of medicine. This pen is a research preparation supplied for laboratory research, and it is not a treatment for anything.

The distinction has practical weight for anyone reading around the compound. Marketing material for peptide therapy tends to describe protocols, cycles and dosing schedules, none of which exist in the published literature for AEDG. The rodent studies used courses given over months in drinking water or by injection at doses set by the investigators, and the human reports used courses of the parent extract as often as the synthetic tetrapeptide. There is no established protocol to import, which is why this page gives increment arithmetic rather than a schedule.

Delta sleep-inducing peptide, DSIP, is worth separating out here because it appears alongside AEDG in the same clinic lists and the same supplier catalogues. DSIP is a nonapeptide isolated from rabbit cerebral venous blood in 1977 and has no sequence relationship to this tetrapeptide. The two compounds share a nominated use, insomnia, and nothing else. Peptide therapies that list both are grouping by claimed effect, not by chemistry.

Published Literature

The list below was verified against primary indexes; nothing in it concerns a preloaded device.

1. Khavinson VKh, Bondarev IE, Butyugov AA. Bull Exp Biol Med. 2003;135(6):590-592. DOI: 10.1023/A:1025493705728 PMID: 12937682
2. Anisimov VN, Khavinson VKh, Popovich IG, et al. Biogerontology. 2003;4(4):193-202. DOI: 10.1023/A:1025114230714
3. Vinogradova IA, Bukalev AV, Zabezhinski MA, et al. Bull Exp Biol Med. 2008;145(4):472-477. DOI: 10.1007/s10517-008-0121-7
4. Araj SK, Brzezik J, Madra-Gackowska K, et al. Int J Mol Sci. 2025;26(6):2691. DOI: 10.3390/ijms26062691 PMID: 40141333
5. Sinjari B, Khavinson V, Diomede F, et al. Molecules. 2020;25(3):609. DOI: 10.3390/molecules25030609
6. Khavinson VKh, Morozov VG. Neuro Endocrinol Lett. 2003;24(3-4):233-240. PMID: 14523363
7. Stephenson RC, Clarke S. J Biol Chem. 1989;264(11):6164-6170. DOI: 10.1016/S0021-9258(18)83327-0 PMID: 2703484
8. Oliyai C, Borchardt RT. Pharm Res. 1993;10(1):95-102. DOI: 10.1023/A:1018981231468

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