Pinealon (EDR)

Three residues, and a gland that is not in the file

Pinealon is Glu-Asp-Arg: glutamic acid, aspartic acid, arginine, free amino and carboxyl termini, nothing appended. PubChem holds it as CID 10273502 with the molecular formula C15H26N6O8 and a molecular weight of 418.40 g/mol, and carries the CAS registry number 175175-23-2, attested within that record by the EPA DSSTox depositor. The registry trail stops there. A search of the FDA Global Substance Registration System returns no substance record and no UNII, and UniChem, queried on the compound's InChIKey, returns chemical-database identifiers only — ChEBI, PubChem, DSSTox and SureChEMBL among them, alongside a commercial supplier aggregator and a compound-probe collection — and no ChEMBL entry. Every identifier on this page comes from a chemical database rather than a regulatory one.

The name points at the pineal gland. The literature points somewhere else. Khavinson's 2020 review in Molecules describes EDR as a tripeptide isolated from Cortexin, which a 2019 paper in Molecular Biology from the same circle characterises as a clinically approved calf cerebral cortex polypeptide complex. That 2019 paper puts the origin differently again: two cortexin derivatives, EDR and the dipeptide DS, were synthesised. Isolation from a tissue extract and design from one are not the same claim about where a molecule came from, and the two accounts are nowhere reconciled. No publication reporting the isolation of Glu-Asp-Arg from pineal tissue, or from any tissue, was located.

One experiment has put this peptide on pineal tissue. Khavinson, Linkova and colleagues applied short peptides to organotypic cultures of pineal gland from three-month-old rats and measured three markers. The abstract names Ala-Glu-Asp-Gly and Lys-Glu-Asp as the peptides that raised the proliferation marker Ki-67, and states that synthesis of the transcription factor CGRP by pinealocytes was stimulated by Ala-Glu-Asp-Gly alone. Glu-Asp-Arg appears in that abstract once, in the sentence recording that expression of the apoptosis marker AIF did not change under any peptide tested. Whatever the compound does, the single published pineal experiment attributed no pineal effect to it.

Where the peptide has been shown to go

The distribution work is one paper and it was done in a dish. Fedoreyeva and colleagues incubated HeLa cells with fluorescein-labelled short peptides — epitalon, pinealon and testagen among them — and recorded fluorescence in cytoplasm, nucleus and nucleolus. The same study measured how the unlabelled peptides quenched fluorescence of labelled deoxyribooligonucleotides and of DNA-ethidium bromide complexes, and reported Stern-Volmer constants that differed with peptide sequence. Pinealon, epitalon and bronchogen bound preferentially to oligonucleotides containing CNG, the context in which eukaryotic cytosine methylation occurs, and the constants distinguished methylated from unmethylated targets. A cervical carcinoma line in culture is the whole of the evidence that this peptide enters a nucleus.

Two later studies pursued the binding rather than the delivery. In 2019 a biophysics group at St Petersburg State University, without Khavinson as an author, examined the EDR-DNA interaction by spectroscopy, NMR, viscosimetry and molecular dynamics, and reported that the peptide can partly enter the major groove and reach the N7 and O6 atoms of guanine, with magnesium promoting the interaction by screening phosphate charge. A 2013 paper reported binding of six short peptides, EDR included, to fluorescein-labelled wheat histones H1, H2B, H3 and H4, the pattern depending on histone, peptide sequence and oligonucleotide. Wheat histones and free DNA in a cuvette establish that the chemistry is possible, not that it occurs in a brain.

Almost everything downstream of that is computational. Khavinson's group has published molecular modelling placing EDR at binding sites in the promoter regions of CASP3, NES, GAP43, APOE, SOD2, PPARA, PPARG and a gene printed as GDX1, and separate docking work reporting that EDR scores better against the LAT1, LAT2 and PEPT1 transporters than most of 8,400 di- and tripeptides with no established activity. Docking scores are affinity hypotheses generated in software. A 2014 report pairs the two modes in one paper: serotonin expression rose in ageing cultures of brain cortex cells under EDR and Lys-Glu-Asp, and a CCTGCC sequence in the tryptophan hydroxylase gene was identified as complementary to the peptides by docking. The measurement and the mechanism sit side by side, joined by no experiment.

Free radicals, and what the antioxidant framing omits

The cell-viability result is the least legible experiment on this compound. Khavinson, Ribakova, Kulebiakin and colleagues reported in Rejuvenation Research in 2011 that pinealon restricted reactive oxygen species accumulation in cerebellar granule cells, neutrophils and PC12 phaeochromocytoma cells under receptor-dependent and receptor-independent oxidative stress, described as dose-dependent, and reduced necrotic death measured by propidium iodide uptake. ERK1/2 activation was delayed and the cell cycle modified. The abstract gives no concentrations, no replicate counts, no effect sizes and no species for the granule cells or the neutrophils; the full text is subscription-only with no PubMed Central deposit and could not be retrieved for this page.

An earlier pair of papers from the same programme complicates the antioxidant reading. Testing pinealon alongside vilon, vesugen and epitalon in vitro, Kozina and colleagues reported that the peptides showed no direct antioxidant activity, that they restricted lipid peroxidation of human lipoproteins by modifying lipoprotein structure instead, and that they raised the stationary level of intracellular reactive oxygen species while lowering the percentage of dead cells in a neuronal population. A companion paper on hypobaric hypoxia named pinealon the most pronounced of the four and attributed the effect to stimulation of endogenous antioxidant enzymes rather than to suppression of the radical rise.

Recent culture work is more precise than its own summary. In 2024 Kraskovskaya and colleagues transdifferentiated dermal fibroblasts from three elderly women, aged 61, 66 and 68, into induced cortical neurons and applied EDR at 10 micrograms per millilitre daily for ten days. Primary processes rose 28% and total dendrite length 46%, both significant. The 8-OHdG marker of oxidative DNA damage fell 23%, at p = 0.0566. The results section calls that decrease statistically significant in one sentence and very close to significant two sentences later, the conclusions call it almost reliable, and the abstract states without qualification that EDR reduces oxidative DNA damage. Mitochondrial activity, lysosomal activity, p16 and lamin B1 did not move.

The rat experiments

Arutjunyan and colleagues ran the one in vivo study that reports its numbers in full. Female Wistar rats were loaded with methionine in drinking water from the second trimester of pregnancy, raising plasma homocysteine roughly five-fold; a third group received pinealon intraperitoneally at 10 micrograms per kilogram daily for five days before the loading began. Six litters per group. Pups of methionine dams weighed 17.86 grams at ten days against 23.05 grams in control, and pups of dams given both weighed 25.03 grams. Offspring homocysteine was not corrected: 5.6 micromolar in control, 9.8 with methionine, 10.5 with methionine and pinealon together.

Behaviour was measured in 23 animals per group at 45 days in a Morris water maze. On the first trial of the second day, intact pups reached the platform in 112 seconds, methionine pups in 170, and methionine-plus-pinealon pups in 137, a figure the authors report as differing from both other groups. Across the remaining trials the gap narrowed, and by the fifth trial all three groups reached the platform in the same time. Cerebellar granule cells taken from ten-day-old pups and challenged with 5 millimolar hydrogen peroxide showed mean DCF fluorescence of 158.7 in the methionine group against 108.6 in the combined group, and 17.7% against 7.0% propidium-iodide-labelled cells.

Not every rodent result runs the same way. In old rats subjected to carotid artery occlusion, Mendzheritskii and colleagues reported that pinealon given beforehand raised behavioural sleep and reduced position-finding behaviour, motivational behaviour and motor performance, and that caspase-3 activity increased moderately both in sham-operated animals and in the occlusion model. Group sizes appear in no abstract in this series. A 2014 report on acute hypoxic hypoxia describes Cortexin as reducing the capacity of brain tissue for programmed cell death while pinealon acted on interleukin-6 and tumour necrosis factor, and a 2015 comparison in 18-month-old rats placed Cortexin ahead of pinealon on free-radical measures and caspase-3.

The Alzheimer's model, and a correction that reached its images

Two publications carry the neuroprotection claim. In 2017, in primary culture of mouse hippocampal neurons under amyloid synaptotoxicity, Kraskovskaya and colleagues reported that EDR at 200 nanograms per millilitre raised the count of mushroom-shaped spines by 71% and returned it to the untreated level, against 20% for the tripeptide KED. Replicate counts do not appear in the abstract. PubMed attaches a correction to that paper at PMID 28975591; it was retrieved and read, and it changes the acknowledgements to name a Russian Science Foundation grant. It touches no datum.

The in vivo version followed in Pharmaceuticals in 2021. 5xFAD-M mice received EDR intraperitoneally at 400 micrograms per kilogram daily from two to four months of age and were examined at five months. Spine density on CA1 secondary dendrites rose 11%, from 11.31 to 12.64 spines per ten micrometres, at p = 0.039. Split by sex, males gained 13% in density and 25% in mushroom spines, at p = 0.019 and p = 0.004; females gained 12% in density with no change in mushroom spines, at p = 0.681. Section 4.2 of the paper gives ten animals per group, five of each sex, so the sex-split result rests on five mice per sex per arm.

That sex difference rests on two figures, and both were replaced. In January 2025 Pharmaceuticals published a correction stating that Figures 5 and 8 of the paper were the same figure described differently. Figure 5 presents confocal images of CA1 secondary dendrites in male M-line and 5xFAD-M mice; Figure 8 presents the female series. The authors supplied corrected versions and stated that the scientific conclusions are unaffected. PubMed types the notice as a published erratum, with no retraction and no expression of concern, and a publication-type and corrections scan across the thirty-one records reviewed for this page returned no other integrity flag.

People, and the registry

Human publications exist, in one journal, in Russian, with no randomisation described. Advances in Gerontology carries an occupational cluster: locomotive-brigade workers given 100-microgram capsules twice daily for two weeks, reported as improving biological-age parameters, with no sample size in the abstract; a work-ability-index comparison; and a 2016 monitoring study across 110 people of different ages setting pinealon and vesugen against dry carbon dioxide baths, hyperbaric oxygen and therapeutic massage. A 2015 study by a Yekaterinburg group enrolled 32 patients aged 41 to 83 with polymorbidity and organic brain syndrome in remission, and describes them in the same sentence as 18 men and 12 women, which is 30.

Two findings in that 2015 report rarely travel with it. Its authors recorded prooxidant activity by chemiluminescence, and a fall in circulating CD34-positive haematopoietic cells that they characterised as significant inhibition of haemopoiesis. They also rated vesugen the more effective of the two peptides. The single publication PubMed types as a clinical trial is a 2012 study of 150 lorry drivers against 150 metal craftsmen, which characterises psychoadaptive disorders in both occupations and then reports, in a closing sentence carrying p values and no arm sizes, that bioregulating peptides restored adaptive potential, best in combination.

ClinicalTrials.gov holds no study of this compound. Queries run on 18 August 2026 returned zero registered studies for pinealon and zero for vesugen; a query for EDR peptide returned one, NCT00848302, an L-arginine endothelial-function study with no relation to this peptide, and a query for Glu-Asp-Arg returned 26 unrelated amino-acid trials, which confirmed the endpoint was live. Pinealon was not among the seven substances before the FDA Pharmacy Compounding Advisory Committee on 23 and 24 July 2026. The first test by a group independent of the St Petersburg institute appeared in 2026 as a preprint from a Swiss contract research group, VivoArchitect, with animal work run through the University of Zaragoza: seven-month-old male C57BL/6J mice, five per group, 30 milligrams per kilogram intraperitoneally twice weekly for eight weeks, screened beside four other candidate interventions. Y-maze alternation and arm entries showed no significant difference from control, and the authors record a trend and label it non-significant. That study is not disinterested either. It was funded by the Pump.Science Association, whose award field names a token bearing this compound's ticker, and a coauthor is affiliated with that association; the abstract advertises the work as the first comprehensive preclinical ageing study in mice fully funded through tokenised decentralised science.

What is not known

No registered human trial of this compound exists anywhere. On 18 August 2026 ClinicalTrials.gov returned zero studies for pinealon and zero for vesugen, and the one record returned for EDR peptide, NCT00848302, is an L-arginine endothelial-function study unrelated to this peptide, so no dose-ranging, pharmacokinetic, safety or efficacy work in people has been registered, let alone reported. Nothing is known about absorption, distribution, metabolism or clearance in any species, which means the relationship between an administered amount and any tissue concentration is unestablished; the intraperitoneal doses in the rodent literature span 10 micrograms per kilogram to 30 milligrams per kilogram, a three-thousand-fold range chosen without any published dose-response study to anchor it. Whether the peptide reaches brain tissue after any route of administration has not been measured. Immunogenicity, reproductive and developmental toxicity, chronic exposure, genotoxicity and carcinogenicity have not been assessed. Group sizes are absent from most of the primary abstracts, several of which are Russian-language reports in a single journal that describe neither randomisation, blinding, nor a placebo arm. The great majority of the record originates with one institute in St Petersburg and its collaborators, so almost nothing here has been produced independently; the one study from outside that circle, an eight-week screen in five mice per group, was itself funded by and coauthored with an association that allocated fees from a token named for this compound, and it found no significant effect. Pinealon is not an approved medicine in any jurisdiction, holds no UNII and no ChEMBL entry, and material sold outside a registered trial has been subject to no identity, purity or sterility control.

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