F tier · safety concern
Pinealon has the largest literature of the five — 22 PubMed-indexed papers — yet zero registered trials on ClinicalTrials.gov and no randomised or placebo-controlled human study anywhere; the human evidence is an open adjunct series of 72 patients described only inside the group's own review plus an uncontrolled 32-patient observation that itself reported prooxidant activity.
pinealon
Pinealon is the best-documented compound of this group: a verified tripeptide, Glu-Asp-Arg, with a PubChem record and a CAS number, and 22 PubMed-indexed publications. The biology is nonetheless preclinical — reactive oxygen species suppression in cultured cells, dendritic spine preservation in 5xFAD Alzheimer's model mice, hypoxia and behaviour experiments in aged rats, and biophysical characterisation of EDR binding in the DNA major groove. Human use is supported only by open-label series in Russian-language gerontology journals, with no randomised or placebo-controlled trial and no trial registration.
// we supply this one
available as a research reagent
≥ 98% HPLC · lyophilised powder · batch certificate published. Grade F above is our own and is not adjusted because we stock it.
the explanation
Pinealon is a three-amino-acid peptide marketed for brain function and memory. Unlike most of its family it is a properly identified chemical with a CAS number, and there is a genuine body of animal and cell work behind it. But no proper clinical trial has ever been run or even registered: the human reports are small studies where everyone knew who got what, and one of them found the peptide increased oxidative stress markers. Almost every biological paper comes from the group that invented it.
regulatory status
No medicinal approval anywhere; Russian dietary supplement; unlicensed in the UK
Pinealon has no marketing authorisation as a medicine in the UK, EU or US, and no MHRA, EMA or FDA assessment exists. A ClinicalTrials.gov query for Pinealon returns zero registered studies. In Russia it is sold within the Cytogens consumer range associated with Khavinson's institute, in capsule, ampoule and sublingual forms, as a dietary supplement rather than a registered medicine. It is not named on the WADA Prohibited List. In the UK it is not a licensed medicine, not a prescription-only medicine, not a controlled drug and not an authorised supplement ingredient; lawful supply is as a laboratory reagent not for human consumption.
how it works · proposed mechanism
The proposed mechanism is direct nuclear action: EDR crosses the cell and nuclear membranes, binds specific promoter regions and histones, and shifts expression of antioxidant, neurotrophic and apoptotic genes. This is the family's best-supported mechanistic claim because the DNA-binding step has been examined by a group with no stake in the biology. What remains unbridged is the distance from binding to clinical benefit.
Nuclear penetration and sequence-selective DNA binding
Fluorescein-labelled EDR was reported to reach the cytoplasm, nucleus and nucleolus of HeLa cells and to interact preferentially with particular oligonucleotide motifs, discriminating cytosine methylation. This is the mechanistic keystone for the whole family, tested here alongside epitalon and testagen.
Independent biophysical corroboration of the binding step
A St Petersburg State University physics group with no Khavinson co-authorship used NMR, spectroscopy, viscometry and simulation to show EDR partly enters the DNA major groove and contacts guanine N7 and O6, with magnesium screening enabling the interaction. This is the closest thing to independent replication anywhere in this family — and it validates a physical interaction, not a therapeutic effect.
Redox and proliferative effects in culture
EDR reportedly reduced reactive oxygen species accumulation and cell death across several cell types, with delayed ERK1/2 activation and cell-cycle changes; because the antioxidant effect plateaued while cell-cycle modulation continued, the authors inferred direct genomic action. The same effect direction was not reproduced in the one human study that measured oxidative markers.
Dendritic spine preservation in an Alzheimer's model
In 5xFAD transgenic mice, EDR increased overall dendritic spine density and reduced thin-spine prevalence, with sex differences in spine pathology; a companion peptide restored mushroom-spine counts. The author list is entirely Russian and headed by Khavinson, so this is an extension of the originating programme rather than a check on it.
what’s reported
evidence shape
7 sourcesThe composition of the cited literature by study type. This describes the shape of the evidence, not its quality — and it does not by itself set the grade.
⚠ the catch
Pinealon is the compound in this family that looks closest to real science and still has no clinical evidence. It has a confirmed structure, a CAS number, 22 indexed papers and one genuinely unaffiliated study — but that study is a physical-chemistry analysis of how the peptide sits in a DNA groove, not a test of whether it helps anyone. ClinicalTrials.gov holds zero registered studies. The headline human claim, 72 patients with post-traumatic cerebrasthenia reporting better memory and fewer headaches, appears as an uncited assertion inside a review written by the peptide's own inventors, with no randomisation, blinding or control described. The only human study whose design can be retrieved enrolled 32 polymorbid patients without a control group and reported, alongside benefit, prooxidant activity and reduced haematopoietic stem cells — the opposite of the antioxidant effect the cell-culture case rests on.
key published findings
- ClinicalTrials.gov contains zero registered studies of Pinealon (verified by registry query).
- Chemistry fully verified: Glu-Asp-Arg, C15H26N6O8, 418.40, CAS 175175-23-2 (PubChem CID 10273502) — the only compound of these five with a confirmed CAS number.
- 22 PubMed-indexed publications name pinealon, more than the rest of this family, but none is a randomised or placebo-controlled human trial.
- The 72-patient open adjunct series in post-traumatic cerebrasthenia is cited without design detail or a formal reference inside Khavinson's own 2020 Molecules review.
- The one human study with retrievable methods enrolled 32 patients aged 41-83 with chronic polymorbidity, uncontrolled, and reported prooxidant activity and reduced haematopoietic stem cells alongside claimed anabolic and CNS benefit.
- One non-Khavinson group (St Petersburg State University, Faculty of Physics) published EDR-DNA interaction work in the ACS Journal of Physical Chemistry B — independent of the originating institute but confirming a binding event, not a biological claim.
limitations of the evidence
- No randomised, blinded or placebo-controlled human trial exists, and none has ever been registered.
- The most-quoted human result (72 patients) is unreferenced within the review that reports it, so its design, comparator and outcome definitions cannot be audited.
- Most human work appears in Advances in Gerontology, a journal closely tied to the originating institute, and includes semi-independent Russian clinical groups using the manufacturer's product rather than truly independent replication.
- Rodent neuroprotection studies frequently co-administer or compare against Cortexin, a registered Russian polypeptide preparation, which risks transferring that product's reputation to EDR.
- The only genuinely unaffiliated study is biophysical; no independent laboratory has reproduced any behavioural, cognitive or clinical claim in two decades.
- Sources overlap with the other Khavinson bioregulators in this index because these compounds are described in one shared body of literature; shared reviews are not independent support.
documented safety signals
- An uncontrolled 32-patient study by the originating family's collaborators reported prooxidant activity and a reduction in haematopoietic stem cells during peptide use — a signal that directly contradicts the antioxidant mechanism claimed for the compound.
- No formal toxicology package, no dose-escalation safety study and no adverse-event surveillance system exist for pinealon.
- The compound is proposed to bind DNA promoter regions and alter transcription; no genotoxicity or long-term carcinogenicity assessment was located, although the same 32-patient report stated chromatin structure was unchanged.
- Absence of other reported harm reflects absence of monitored human exposure rather than demonstrated safety.
identity
| full name | Pinealon (L-glutamyl-L-aspartyl-L-arginine; Glu-Asp-Arg, EDR) |
| category | Cognitive |
| modality | peptide |
| formula | C15H26N6O8 |
| molar mass | 418.4 g/mol |
| cas | 175175-23-2 |
| sequence | Glu-Asp-Arg (EDR) |
laboratory handling
| storage | Lyophilised powder is stored desiccated at -20 °C and protected from light. Once reconstituted, laboratory practice is refrigeration at 2-8 °C for short-term use, or aliquoting and freezing to avoid repeated freeze-thaw cycles. Handling information only; this material has no approved human use. |
| solubility | Short hydrophilic peptide, readily soluble in sterile or bacteriostatic water and in dilute aqueous buffer. Lot-specific solubility is stated on the certificate of analysis. |
| co-studied with | Rodent studies and the retrievable human observation used pinealon together with other short peptides such as Vesugen or with the registered preparation Cortexin, so reported effects cannot be attributed to pinealon alone. |
Handling information describes laboratory practice for a research reagent. It is not a preparation guide for use in humans.
the receipts
7 citedPubChem, NCBI · 2026 · official
ClinicalTrials.gov, US National Library of Medicine · 2026 · official
Molecules · 2020 · review
Rejuvenation Research · 2011 · preclinical
Pharmaceuticals · 2021 · preclinical
Journal of Physical Chemistry B · 2019 · preclinical
Advances in Gerontology · 2015 · observational
others in Cognitive