Pinealon 10mg Peptide

Pinealon is the synthetic tripeptide Glu-Asp-Arg: three residues, formula C15H26N6O8, 418.40 g/mol, CAS 175175-23-2, PubChem CID 10273502. It came out of the St Petersburg Institute of Bioregulation and Gerontology, from the programme run by Vladimir Khavinson that also produced Epithalon (Ala-Glu-Asp-Gly) and Vesugen (Lys-Glu-Asp). In the group's own English-language reviews the EDR sequence is described as a constituent of Cortexin, a polypeptide preparation manufactured from the cerebral cortex of cattle and pigs. The name points at the pineal gland. The reported provenance points at the cortex.

Everything written about the compound rests on one premise: that a peptide this short can cross the plasma membrane and the nuclear envelope intact, contact DNA and histones directly, and change which genes are transcribed, with no receptor anywhere in the chain. That premise is the mechanism. There is no second candidate mechanism in the literature, and the 2021 paper from the originating group states in its own conclusions that the exact mechanism of action is unknown.

The evidence base is small and geographically concentrated. A PubMed search for pinealon in August 2026 returns 22 records, two of which concern unrelated compounds. Twelve of the remaining twenty sit in Advances in Gerontology, a Russian-language journal published in St Petersburg, and most of the rest carry Khavinson as an author. ClinicalTrials.gov returns no study of this peptide under any of its names, and no pharmacokinetic study has been published in any species.

No receptor has been identified for Glu-Asp-Arg, and none is proposed. The model is direct nucleic acid and chromatin contact, assembled from three separate kinds of evidence: biophysical measurement of peptide binding to DNA, fluorescence imaging of labelled peptide reaching the nucleus, and computational docking of the tripeptide against promoter sequences. None of it is a solved co-crystal structure, and the group that developed the peptide says as much in print.

The strongest physical evidence is also the only substantial contribution from outside the originating institute. A 2019 study at the physics faculty of St Petersburg State University combined absorption spectroscopy, NMR, viscometry and molecular dynamics on EDR mixed with DNA. The peptide partly penetrates the major groove and interacts with base atoms, principally the N7 and O6 positions of guanine. Magnesium ions promote the interaction by screening the negative charge on the DNA phosphate backbone, and that effect persists in salt solution. The work establishes that binding happens and where. It says nothing about whether binding changes transcription in a living cell.

Nuclear access was shown by fluorescence. Fluorescein-labelled EDR, alongside labelled Epithalon and Testagen, produced marked signal in the cytoplasm, nucleus and nucleolus of HeLa cells. In the same study, Stern-Volmer quenching constants against a panel of labelled deoxyribooligonucleotides showed the peptides discriminating between nucleotide sequences and even between methylated and unmethylated cytosine at the same site. EDR bound preferentially to CNG-containing sequences and, among those, to CAG. A companion study extended the binding to wheat histones H1, H2B, H3 and H4, with the interaction assigned to N-terminal histone regions.

The promoter map is computed rather than measured. The 2021 mouse study docked EDR against every unique hexanucleotide double-stranded DNA sequence, 2080 of them, then matched the lowest-energy complexes against human promoter sequences from the EPD database. Hits fell in the promoter regions of CASP3, NES, GAP43, APOE, SOD2, GPX1, PPARA and PPARG. A 2020 review names the two binding motifs as d(CCTGCC)2 and d(CCAGC)2 and adds TPH1, the rate-limiting enzyme of serotonin synthesis. Every one of those genes was selected because it already had a role in the pathology being studied, which is a real limitation of the approach.

Downstream, the measured cellular outputs are consistent across models even where the statistics are thin. In rat cerebellar granule cells, neutrophils and PC12 cells, EDR restricted reactive oxygen species accumulation dose-dependently under both receptor-dependent stress, from ouabain or homocysteine, and receptor-independent stress from hydrogen peroxide, and reduced necrotic death measured by propidium iodide uptake. It pushed the ERK1/2 activation that homocysteine normally triggers within 2.5 minutes out to roughly 20 minutes. In hypoxia-sensitive rats it raised brain SOD2 and glutathione peroxidase 1 activity to the level seen in hypoxia-resistant animals, which already ran about twice as high untreated.

The excitotoxicity claim deserves precision, because it is usually restated as a calcium effect and no calcium measurement exists. The 2008 antihypoxic work proposed that the protection rests less on inhibiting the radical rise than on stimulating the endogenous antioxidant enzyme system, and possibly on limiting the excitotoxic effect of N-methyl-D-aspartate. Homocysteine and NMDA both act at the NMDA receptor, which is the calcium-entry channel, so the inference is reasonable. What was actually measured in those experiments was reactive oxygen species, ERK1/2 phosphorylation and cell death. No published study reports intracellular calcium in EDR-treated neurons.

Both of the originating group's English-language papers describe EDR the same way. The 2020 review calls it a tripeptide isolated from Cortexin, a polypeptide neuroprotective preparation, and the 2021 mouse study repeats that the peptide is found in Cortexin. Cortexin is manufactured from the cerebral cortex of cattle and pigs. It is not a pineal product, and nothing in the indexed literature reports EDR being isolated from pineal tissue.

The group's own pineal experiment argues in the same direction. In 2011 they applied four short peptides to organotypic culture of pineal gland from 3-month-old rats and measured proliferation, apoptosis and secretory markers. Ala-Glu-Asp-Gly and Lys-Glu-Asp raised expression of the proliferation protein Ki-67 in pinealocytes. Glu-Asp-Arg did not. None of the peptides, including EDR, changed the apoptosis marker AIF, and CGRP synthesis by pinealocytes was stimulated by Ala-Glu-Asp-Gly alone. In the single published experiment run on pineal tissue itself, EDR was the peptide that did nothing.

That matters for how the melatonin and circadian framing should be read. No published experiment measures melatonin, 6-sulfatoxymelatonin or any clock gene after EDR. The association travels by name and by proximity to Epithalon, which does have pineal literature attached to it, some of which in turn belongs to a bovine pineal extract rather than to the tetrapeptide.

Five compounds from this programme are sold side by side and their sequences are reported inconsistently across secondary sources. The ones that can be pinned down from primary literature and structure databases are these. Epithalon is Ala-Glu-Asp-Gly, C14H22N4O9, 390.35 g/mol, CAS 307297-39-8. Pinealon is Glu-Asp-Arg, C15H26N6O8, 418.40 g/mol, CAS 175175-23-2. Vesugen is Lys-Glu-Asp, C15H26N4O8, 390.39 g/mol, named as KED throughout the 2021 mouse paper. Cardiogen is Ala-Glu-Asp-Arg, which appears in the title of a 2012 Bulletin of Experimental Biology and Medicine paper as H-Ala-Glu-Asp-Arg-OH.

Cortagen is the one that does not survive checking. Catalogues and secondary sources widely print its sequence as Ala-Glu-Asp-Leu. PubChem's Cortagen record, CID 18439621, gives C17H26N4O9 at 430.4 g/mol with CAS 335591-03-2. Ala-Glu-Asp-Leu is C18H30N4O9 at 446.5 g/mol, so the two cannot be the same molecule, and in the Khavinson group's own papers the Ala-Glu-Asp-Leu sequence is named Bronchogen. Anyone comparing Pinealon with Cortagen should treat the AEDL attribution as unverified rather than as a fact.

The trap that catches product listings most often is Pinealon against Cardiogen. Glu-Asp-Arg and Ala-Glu-Asp-Arg differ by a single N-terminal alanine, 71 daltons, while their trade names look nothing alike and point at different organs. Their reported biology diverges as well: the tetrapeptide was reported in 2012 to raise actin, tubulin and vimentin expression 2 to 5-fold and lamin A and lamin C 2 to 3-fold in cultured mouse embryonic fibroblasts, a cytoskeletal and nuclear-matrix result with no counterpart anywhere in the EDR literature.

There is an analytical consequence too. Vesugen at 390.39 g/mol and Epithalon at 390.35 g/mol are separated by 0.037 daltons at the monoisotopic level. A nominal-mass instrument reports both as 390 and cannot tell them apart; separating them needs high-resolution mass spectrometry or amino acid analysis. Pinealon at 418.40 is comfortably distinct from both, but not from Cardiogen on retention behaviour alone.

The antihypoxic work is where the compound's reputation comes from. In a hypobaric hypoxia model, four short peptides were compared and pinealon produced the most pronounced effect of the group. The author's own reading of the mechanism is worth taking literally: the protection was attributed not so much to inhibiting the ROS rise in response to stress as to stimulating the internal antioxidative enzyme system, and possibly to limiting the excitotoxic effect of N-methyl-D-aspartate. That is a statement about enzyme induction, not about radical scavenging.

The prenatal work took a different route. Pregnant rats were loaded with dietary methionine to raise homocysteine, and the peptide was given to the dam. What was then measured was in the pups: spatial orientation and learning ability, and, in cerebellar neurons isolated from those pups, reactive oxygen species accumulation and the proportion of necrotic cells. Both improved relative to untreated hyperhomocysteinaemic litters. The design is the interesting part and also the limitation, because the exposure the pup actually received was never quantified.

A related result reported in the 2020 review makes the hypoxia model concrete. Hypoxia tripled the baseline ROS level in offspring neurons, and against that raised background NMDA produced no further increase, which is what a saturated excitotoxic state looks like. EDR treatment lowered radical levels in those neurons. Separately, SOD2 and GPX1 activity in hypoxia-resistant rats ran roughly twice that of hypoxia-sensitive animals, and EDR raised the sensitive animals to the resistant level while adding nothing in animals that were already high.

One companion paper from the same author, in the same year and the same journal, points the other way and is almost never cited alongside the rest. Testing pinealon, vesugen, vilon and epitalon in model systems, it found that the peptides showed no direct antioxidant activity at all, that they restricted lipid peroxidation of human lipoproteins only by modifying lipoprotein structure, and that they raised the stationary level of intracellular reactive oxygen species while simultaneously lowering the percentage of dead cells in the neuronal population. A compound that raises steady-state ROS and cuts cell death at the same time is not behaving as an antioxidant, and the authors said so.

The 2021 mouse study is the most rigorous in vivo work on this peptide and it repays reading closely rather than in summary. 5xFAD mice, carrying three APP mutations and two PSEN1 mutations, were crossed with a Thy1-EGFP reporter line so that individual dendritic spines could be counted by confocal microscopy. EDR was given at 400 micrograms per kilogram intraperitoneally once daily for two months, from 2 to 4 months of age, with 10 animals per group split evenly between sexes.

The spine density result held up. CA1 apical dendrite spine density rose from 11.31 plus or minus 0.36 to 12.64 plus or minus 0.31 spines per 10 micrometres, an 11% increase at p = 0.039, restoring it to the reporter-line control level. Thin spines, which accumulate as mushroom spines are lost, fell 10% at p = 0.024. Mushroom spines themselves, which the paper argues are the memory-bearing population, did not change significantly across the whole cohort at p = 0.053, although in males considered alone they rose 25% at p = 0.004. The sex stratification was not pre-specified.

The electrophysiology did not work. Long-term potentiation was measured in hippocampal slices after high-frequency stimulation of Schaffer collaterals, and the difference between transgenic and wild-type animals reached only p = 0.057. The experiment therefore failed to establish the deficit it was designed to rescue, and the peptide effects on LTP are reported as trends rather than results. A correction to this paper was published in the same journal in January 2025.

The 2024 induced-neuron study is the newest and uses a genuinely different model: dermal fibroblasts from three donors aged 61, 66 and 68 were directly reprogrammed into induced cortical neurons with MYT1L and NeuroD2, then treated with EDR at 10 micrograms per millilitre for 10 days. Primary dendritic processes rose 28% at p = 0.0208 and total process length rose significantly. The headline claim, reduced oxidative DNA damage, is a 23% fall in 8-hydroxydeoxyguanosine staining at p = 0.0566. The paper's own text calls that very close to significant; the abstract states it as a reduction. Mitochondrial membrane potential, lysosomal activity, p16 and lamin B1 were all unchanged.

There is no registered trial. A search of ClinicalTrials.gov in August 2026 returns zero studies for pinealon, and nothing relevant for EDR peptide or Glu-Asp-Arg. What exists instead is a set of small open-label series published in Advances in Gerontology and summarised in the group's English-language reviews.

The most detailed is a 2015 report on 32 people aged 41 to 83 with chronic polymorbidity and organic brain syndrome in remission, given pinealon or vesugen. The authors reported a significant anabolic effect and improved central nervous system activity, slowing biological-age indicators, and concluded that vesugen produced the more visible effect of the two. The same abstract records two findings that rarely travel with the summary: prooxidant activity detected by chemiluminescence, and a significant fall in circulating CD34-positive haematopoietic cells, which the authors read as inhibition of haemopoiesis.

The occupational studies are narrower in what they can attribute. In one, locomotive crew workers took capsules containing 100 micrograms of pinealon twice daily for two weeks, with reported improvement in biological-age parameters and adaptive-reaction indicators, and no control arm described. In another, 150 lorry drivers were compared with 150 metal craftsmen, and the best result came from combining pinealon with vesugen, which means nothing in that arm can be assigned to EDR alone. A traumatic brain injury series of 72 patients receiving oral EDR on top of standard therapy reported improved memory and a rise in the EEG alpha index, again uncontrolled.

The pharmacological gap under all of this is delivery. These reports use an oral or capsule route for a three-residue peptide with two free termini and no protecting groups, in a gut whose job is to hydrolyse exactly that. No absorption study, no plasma concentration and no bioavailability figure has been published for EDR by any route, so the reported oral effects have no measured exposure standing behind them.

Three carboxyl groups, from the glutamate and aspartate side chains and the free C-terminus, sit against one arginine guanidinium and the free alpha-amine, giving a net charge near -1 at physiological pH. The computed descriptors follow from that: XLogP -6.1, topological polar surface area 261 square angstroms, 8 hydrogen bond donors and 10 acceptors, 14 rotatable bonds. This is about as polar as a three-residue molecule gets, and it dissolves readily in water and aqueous buffer with no organic co-solvent needed.

Both termini are unprotected, which makes the molecule a substrate for aminopeptidases at one end and carboxypeptidases at the other. Nothing has been published on its stability in plasma, serum or aqueous solution over time, so every half-life figure in circulation is inference rather than measurement. The practical handling risk with the solid is water rather than chemistry: the two acidic side chains make the lyophilised cake hygroscopic, so a cold vial opened in humid air takes up moisture before the powder is touched.

For identity, the useful numbers are the monoisotopic mass, 418.1812 daltons, and the corresponding singly protonated ion at m/z 419.19 under positive-mode electrospray. Reversed-phase HPLC area purity, which is what a typical certificate reports, answers a question about how much of the material is one thing, not about which thing it is. It will not reliably separate Glu-Asp-Arg from Ala-Glu-Asp-Arg, and it will not catch a substituted sequence at all. Amino acid analysis or MS/MS sequencing closes that gap, and neither appears on most certificates supplied with this compound.

Third-party assay reports for material sold under this name do exist and cluster above 99% by HPLC area. That is a useful signal about manufacturing consistency and a weak one about identity, which is the specific failure mode worth guarding against in a family where five compounds share an Asp-Glu core and two of them differ by a single residue.

No receptor, no protein binding partner, and no solved structure of the peptide bound to anything. The DNA contact model is supported by spectroscopy, molecular dynamics and docking, and the originating group's most recent in vivo paper states in its own conclusions that the exact mechanism of action is unknown.

No pharmacokinetics of any kind. There is no measured half-life, no clearance, no bioavailability by any route, no tissue distribution and no brain-to-plasma ratio. Brain penetration is asserted on essentially every product listing. What supports it is indirect: systemically administered EDR changed brain caspase-3 activity and hippocampal spine density in rodents, so something reached the brain. No study has measured a concentration there or named a transporter.

No registered clinical trial and no controlled human study of any design. The human material is uncontrolled, open-label and published in Russian, and in the largest series the compound was outperformed by its sibling peptide while producing a prooxidant chemiluminescence signal and a fall in a haematopoietic stem cell marker.

No independent replication of the central gene-regulation claim. The one substantial piece of work from outside the network, the 2019 DNA binding study, came from a physics faculty and tested binding, not biology. That is the exact shape of the gap: the physical premise has independent support, and everything built on top of it does not.

No dose-response in a mammal linking a systemic exposure to a measured brain concentration to a functional readout. Until that exists, the rodent effect sizes, which mostly sit between 10% and 30% with p values falling on both sides of 0.05, are the ceiling of what this literature can support.