Pinealon
Published research and evidence base
Pinealon is the synthetic tripeptide Glu-Asp-Arg (EDR), one of the short peptide bioregulators developed by Khavinson and colleagues at the St Petersburg Institute of Bioregulation and Gerontology. The proposed mechanism is epigenetic: the peptide is described as entering the nucleus and binding specific DNA sequences and histone proteins, thereby modulating expression of genes involved in apoptosis, antioxidant defence and neuroplasticity. The available evidence is almost entirely in vitro or rodent work from this single research group, supplemented by molecular-modelling studies; controlled human data are limited to small Russian occupational and geriatric studies of peptide combinations rather than EDR alone.
- Studies cited
- 18
- Published 2023+
- 3
- Newest paper
- 2024
- Last reviewed
- Aug 2026
Recurring themes in the literature
- ultrashort peptide bioregulator
- Glu-Asp-Arg / EDR
- epigenetic gene regulation
- peptide-DNA interaction
- oxidative stress and ROS
- dendritic spine preservation
- geroprotection
- Alzheimer's disease models
Compound identifiers
- CAS
- 175175-23-2
- PubChem
- 10273502
What Pinealon is, chemically.
- Molecular formula
- C15H26N6O8
- Molecular weight
- 418.40 g/mol
- CAS number
- 175175-23-2
- PubChem CID
- 10273502
These figures come from the PubChem record for this compound and describe the free base. Lyophilised peptide is normally supplied as an acetate or trifluoroacetate salt and carries residual water, so the mass of powder in a vial is not the same quantity as the molecular weight above would suggest. Chromatographic purity on a certificate of analysis does not resolve that difference either — how to read a certificate of analysis explains why.
18 published studies.
Ordered by strength of study design, then by recency. Every entry links to its source record so the finding can be checked against the paper rather than taken on our word.
- 01Human clinical2012· Russian (English abstract)
[The peptide correction of neurotic disorders among professional truck-drivers]
Bashkireva AS, Artamonova VG · Advances in Gerontology (Uspekhi Gerontologii) · occupational clinical trial, 150 male lorry drivers (mean age 43.3) and 150 male metal craftsmen as controls; peptide bioregulators including pinealon and vezugen
Application of bioregulating peptides was reported to improve psychoemotional indices and reduce occupational risk of borderline mental disorders, with the best effect from combined pinealon and vezugen. Pinealon was not tested alone and the design was not placebo-controlled.
- 02Animal in vivo2021
Neuroprotective Effects of Tripeptides-Epigenetic Regulators in Mouse Model of Alzheimer's Disease
Khavinson V, Ilina A, Kraskovskaya N, Linkova N, Kolchina N, Mironova E, Erofeev A, Petukhov M · Pharmaceuticals · 5xFAD transgenic mice, daily intraperitoneal KED at 400 microg/kg from 2 to 4 months of age, plus molecular docking of peptides to dsDNA
KED and EDR prevented dendritic spine loss in 5xFAD-M mice. Docking identified EDR binding sites in promoter regions of CASP3, NES, GAP43, APOE, SOD2, PPARA, PPARG and GDX1. A correction to this article was published in 2025 (PMID 39861198).
- 03Animal in vivo2015· Russian (English abstract)
[Pinealon and Cortexin influence on behavior and neurochemical processes in 18-month aged rats within hypoxia and hypothermia]
Mendzheritsky AM, et al. · Advances in Gerontology (Uspekhi Gerontologii) · 18-month-old rats under acute hypobaric hypoxia and moderate hypothermia
Cortexin had a stronger effect than Pinealon on free-radical processes and brain caspase-3 activity. Both promoted accumulation of adrenergic mediators under hypoxia and of cortical serotonin under moderate hypothermia.
- 04Animal in vivo2014· Russian (English abstract)
[Regulation of content of cytokines in blood serum and of caspase-3 activity in brains of old rats in model of sharp hypoxic hypoxia with Cortexin and Pinealon]
Mendzheritskii AM, Karantysh GV, Ryzhak GA, Dem'ianenko SV · Advances in Gerontology (Uspekhi Gerontologii) · old rats, acute hypoxic hypoxia model; brain caspase-3 activity, serum IL-6 and TNF
Under brain hypoxia Pinealon was reported to shift neuroinflammatory markers toward reference values, whereas Cortexin reduced programmed cell death but left IL-6 elevated.
- 05Animal in vivo2012
Pinealon protects the rat offspring from prenatal hyperhomocysteinemia
Arutjunyan A, Kozina L, Stvolinskiy S, Bulygina Y, Mashkina A, Khavinson V · International Journal of Clinical and Experimental Medicine · rat offspring of dams with methionine-loading-induced hyperhomocysteinaemia during pregnancy; behavioural testing and cerebellar neuron assays
Pinealon given to pregnant rats improved offspring spatial orientation and learning and reduced reactive oxygen species accumulation and necrotic cell counts in isolated cerebellar neurons.
- 06In vitro2024
Short Peptides Protect Fibroblast-Derived Induced Neurons from Age-Related Changes
Kraskovskaya N, Linkova N, et al. · International Journal of Molecular Sciences · induced cortical neurons transdifferentiated from dermal fibroblasts of elderly human donors; EDR, KED and AEDG peptides
All three peptides promoted dendritic arborisation, increasing the number of primary processes and total dendrite length. EDR specifically reduced oxidative DNA damage, while none of the peptides affected mitochondrial or lysosomal activity or p16 levels.
- 07In vitro2023
Feasibility of Transport of 26 Biologically Active Ultrashort Peptides via LAT and PEPT Family Transporters
Khavinson VK, Linkova NS, Rudskoy AI, Petukhov MG · Biomolecules · molecular modelling and computational docking of 26 ultrashort peptides against LAT1, LAT2 and PEPT1 transporters, benchmarked against 8400 di- and tripeptides
EDR was among the peptides showing the highest predicted binding to LAT1, LAT2 and PEPT1, exceeding known substrates and inhibitors. The work is computational and the predicted transport has not been experimentally confirmed for EDR.
- 08In vitro2019
Role of Mono- and Divalent Ions in Peptide Glu-Asp-Arg-DNA Interaction
Silanteva IA, Komolkin AV, Morozova EA, Vorontsov-Velyaminov PN, Kasyanenko NA · The Journal of Physical Chemistry B · spectroscopy, NMR, viscosimetry and molecular dynamics of EDR-DNA binding
EDR partly penetrated the major groove of DNA and contacted guanine N7 and O6 atoms, with Mg2+ promoting the interaction by screening phosphate charge. This provides the most direct physical evidence for the proposed peptide-DNA mechanism.
- 09In vitro2014
Short peptides stimulate serotonin expression in cells of brain cortex
Khavinson VKh, Lin'kova NS, Tarnovskaya SI, Umnov RS, Elashkina EV, Durnova AO · Bulletin of Experimental Biology and Medicine · ageing brain cortex cell cultures plus molecular docking of peptide to the tryptophan hydroxylase gene
Glu-Asp-Arg and Lys-Glu-Asp increased serotonin expression in ageing cortical cell cultures. Docking identified a CCTGCC sequence in the 5-tryptophan hydroxylase gene complementary to these peptides.
- 10In vitro2013
Interaction of short peptides with FITC-labeled wheat histones and their complexes with deoxyribooligonucleotides
Fedoreyeva LI, et al. · Biochemistry (Moscow) · fluorescence binding assays with FITC-labelled histones and deoxyribooligonucleotide complexes
Short peptides including EDR bound histone proteins and histone-oligonucleotide complexes, supporting the proposed chromatin-level interaction.
- 11In vitro2012
Effect of bioregulatory tripeptides on the culture of skin cells from young and old rats
Voicekhovskaya MA, et al. · Bulletin of Experimental Biology and Medicine · skin cell cultures from young and old rats treated with bioregulatory tripeptides
Bioregulatory tripeptides altered proliferative behaviour of skin cell cultures with age-dependent differences, part of the group's broader tissue-specificity claim for short peptides.
- 12In vitro2011
Penetration of short fluorescence-labeled peptides into the nucleus in HeLa cells and in vitro specific interaction of the peptides with deoxyribooligonucleotides and DNA
Fedoreyeva LI, et al. · Biochemistry (Moscow) · HeLa cells with fluorescence-labelled short peptides; DNA and oligonucleotide binding assays
Fluorescently labelled short peptides entered the nucleus of HeLa cells and showed sequence-specific interaction with deoxyribooligonucleotides and DNA in vitro.
- 13In vitro2011
Pinealon increases cell viability by suppression of free radical levels and activating proliferative processes
Khavinson V, Ribakova Y, Kulebiakin K, Vladychenskaya E, Kozina L, Arutjunyan A, Boldyrev A · Rejuvenation Research · cerebellar granule cells, neutrophils and PC12 cells under receptor-dependent and receptor-independent oxidative stress
Pinealon dose-dependently restricted reactive oxygen species accumulation and reduced necrotic cell death, with delayed ERK1/2 activation and cell cycle modification. The authors concluded that cell-cycle effects at higher concentrations imply direct interaction with the genome beyond antioxidant activity.
- 14In vitro2011
Effect of short peptides on expression of signaling molecules in organotypic pineal cell culture
Khavinson VKh, et al. · Bulletin of Experimental Biology and Medicine · organotypic pineal cell culture
Short peptides including EDR altered expression of signalling molecules in organotypic pineal cell culture, the model from which the Pinealon trade name derives.
- 15Review2024· Russian (English abstract)
[Prospects for use of short peptides in pharmacotherapeutic correction of Alzheimer's disease.]
Ilina AR, Popovich IG, Ryzhak GA, Khavinson VK · Advances in Gerontology (Uspekhi Gerontologii) · narrative review of short peptides in Alzheimer's disease therapy
The review described Glu-Asp-Arg among a set of short peptides (with Leu-Ile, Glu-Trp, Lys-Glu, Gly-Pro, Lys-Glu-Asp and Semax) proposed as multitarget agents for Alzheimer's disease, arguing for a combination rather than single-target strategy.
- 16Review2022
Neuroepigenetic Mechanisms of Action of Ultrashort Peptides in Alzheimer's Disease
Ilina A, Khavinson V, Linkova N, Petukhov M · International Journal of Molecular Sciences · narrative review of epigenetic mechanisms
The authors set out the hypothesis that ultrashort peptides regulate gene expression through interaction with histone proteins, cis- and trans-regulatory DNA elements and DNA/RNA-binding proteins. The mechanism is presented explicitly as a hypothesis.
- 17Review2020
EDR Peptide: Possible Mechanism of Gene Expression and Protein Synthesis Regulation Involved in the Pathogenesis of Alzheimer's Disease
Khavinson V, Linkova N, Kozhevnikova E, Trofimova S · Molecules · mechanistic review of EDR peptide in Alzheimer's disease pathogenesis
The review proposed that EDR enters cells and binds histone proteins or nucleic acids, altering MAPK/ERK signalling and synthesis of caspase-3, p53, SOD2, GPX1, PPARA and PPARG. The authors described improved memory in elderly patients as a prior finding without presenting new controlled trial data.
- 18Review2013· Russian (English abstract)
[Neuroprotective effects of peptides bioregulators in people of various age]
Umnov RS, et al. · Advances in Gerontology (Uspekhi Gerontologii) · review of peptide bioregulators including EDR in human populations of different ages
The review summarised claims of neuroprotective effects of peptide bioregulators across age groups. It is a narrative synthesis from the originating research group rather than an independent evaluation.
What this evidence does not establish.
There is no randomised, placebo-controlled trial of Pinealon or EDR alone in humans, no pharmacokinetic data, and no demonstration that orally or parenterally administered EDR reaches brain tissue intact at physiologically relevant concentrations. Essentially the entire body of evidence originates from one research group in St Petersburg, and the central epigenetic mechanism rests on molecular docking and in vitro binding rather than in vivo target engagement. Independent replication outside this group is effectively absent.
Common questions about the research.
- What is Pinealon?
Pinealon is the synthetic tripeptide Glu-Asp-Arg, abbreviated EDR. It belongs to the family of short peptide bioregulators developed by the Khavinson group in St Petersburg, which also includes Epithalon.
- How strong is the evidence base?
Thin. The published record is small, largely produced by one research school, and short on independent replication. In vitro nuclear-penetration and free-radical findings are the most concrete results; the human reports are observational rather than randomised. Treat any account of Pinealon's activity as provisional.
- What is the proposed mechanism?
The bioregulator literature proposes an epigenetic mode of action: short peptides entering the cell nucleus and interacting with specific double-stranded DNA sequences to influence transcription, rather than binding a cell-surface receptor. Supporting evidence exists in cell-free and cell-culture systems; it has not been demonstrated to operate this way in intact human tissue.
Available from our catalog
For research purposes only. Not for human consumption, diagnosis, treatment, or prevention of any condition. Nothing on this page is medical advice, and no study summarised here should be read as a recommendation.