Pinealon is the synthetic tripeptide Glu-Asp-Arg, often abbreviated EDR. It comes from the same family of very short “peptide bioregulators” as Epithalon, developed by Russian gerontology groups that sought defined synthetic peptides to replace crude tissue extracts. Despite the name, Pinealon is studied mostly in connection with the brain and nervous tissue rather than the pineal gland.
Its literature is modest in size and centers on oxidative stress in cultured cells, rodent models of prenatal and ischemic injury, and a proposed mechanism in which the peptide acts on gene expression directly. This article sets out the peptide’s background, the cell and animal findings, the gene-regulation hypothesis, and the reasons for caution when reading the evidence.
At a glance
- Class: Synthetic tripeptide; short “peptide bioregulator”
- Origin: Developed by Vladimir Khavinson’s research network in St. Petersburg (Khavinson et al., 2011)
- Structure: Glu-Asp-Arg; C15H26N6O8; 418.4 g/mol; CAS 175175-23-2
- Main research areas: oxidative stress and cell viability, prenatal hyperhomocysteinemia in rats, serotonin expression in cortical cultures, peptide–DNA interaction hypotheses
- Regulatory status: Not FDA approved for any use
Structure and origin
The bioregulator program began with organ extracts, such as preparations from pineal, thymus and brain tissue, that were difficult to standardize. Researchers then looked for di-, tri- and tetrapeptides that might reproduce the extracts’ reported activity in a defined form. EDR was one of the peptides associated with nervous tissue, and it has been studied alongside related short peptides from the same group.
The molecule contains two acidic residues, glutamate and aspartate, followed by arginine, which carries a strongly basic guanidinium group. At physiological pH it is a small, charged, water-soluble molecule of about 418 g/mol. That small size is central to how its developers think it works: they have argued that peptides this short can cross cell membranes and even the nuclear envelope, then bind DNA. The group has examined this with labeled peptides in cultured cells and in biophysical binding studies, and developed it further in a 2020 modeling paper (Khavinson et al., 2020).
Mechanism: what the research shows
Two lines of evidence are used to explain Pinealon’s reported activity. The first concerns oxidative stress. Khavinson and colleagues exposed cultured cells to oxidative challenges and reported that EDR was associated with lower levels of reactive oxygen species, higher cell viability and changes in cell-cycle and proliferation markers (Khavinson et al., 2011). The authors argued that these effects were not fully explained by direct antioxidant chemistry, which led them to propose a gene-regulatory mechanism.
The second concerns that gene-regulatory hypothesis. A 2020 paper in Molecules combined earlier experimental data with molecular modeling to propose that EDR binds particular DNA sequences in gene promoter regions and could thereby influence expression of genes linked to neurodegeneration, including pathways relevant to Alzheimer’s disease models (Khavinson et al., 2020). This is a hypothesis built largely on computational and indirect data, and no receptor or confirmed binding site has been demonstrated in living tissue.
The two lines of evidence are not mutually exclusive. A small charged peptide could act partly as a direct scavenger or metal-binding molecule and partly through other pathways, and separating these possibilities would require controls, such as scrambled-sequence peptides and inactive analogs, that are not consistently reported in the published work.
Key areas of study
Oxidative stress in cell culture
Cultured cells challenged with oxidants are the basic model, with reactive oxygen species, viability and proliferation as the main readouts (Khavinson et al., 2011).
Prenatal hyperhomocysteinemia in rats
Arutjunyan and colleagues induced elevated homocysteine in pregnant rats, a model of a metabolic disturbance associated with oxidative damage to developing tissue. Offspring from Pinealon-treated dams were assessed for oxidative-stress markers in the brain and for performance in behavioral tests (Arutjunyan et al., 2012).
Serotonin expression in cortical cultures
Short peptides including EDR were tested in cultures of brain cortex cells, where the authors measured serotonin expression (Khavinson et al., 2014). This study is one basis for interest in the peptide in neurochemical research.
Gene regulation modeling
Docking and modeling studies propose DNA binding sites for EDR and predict downstream effects on gene expression, framing hypotheses that would need direct experimental confirmation (Khavinson et al., 2020).
What the evidence does not show
- All published work is preclinical: cell culture, rodent models and computer modeling. None of it establishes effects on cognition, the brain or aging in people.
- Almost all studies come from one network of collaborating laboratories, and independent replication is scarce.
- The proposed mechanism, direct binding of a tripeptide to DNA in the nucleus, has not been confirmed by structural studies in cells.
- Studies are generally small, and concentration-response and mechanism data are rarely reproduced across designs.
- Several reports test EDR together with other short peptides, so the contribution of Pinealon itself is not always separable.
- Pinealon is not an approved drug in the United States.
Regulatory status
Pinealon is not approved by the FDA for any use. Rogue Compounds sells it as a research reagent only, not for human use.
Handling and storage in the lab
Lyophilized Pinealon should be kept sealed and refrigerated at 2–8°C (36–46°F), protected from light.
Sourcing and documentation
Rogue Compounds has Pinealon made in small batches. Every vial carries a batch number and a QR code that opens the independent U.S. testing lab’s own report for that batch, and the same batch COA is on the product page and in the COA Library.
View Pinealon on Rogue Compounds
References
- Khavinson V, et al. Pinealon increases cell viability by suppression of free radical levels and activating proliferative processes. Rejuvenation Res. 2011;14(5):535-541. PMID 21978084
- Arutjunyan A, et al. Pinealon protects the rat offspring from prenatal hyperhomocysteinemia. Int J Clin Exp Med. 2012;5(2):179-185. PMID 22567179
- Khavinson VKh, et al. Short peptides stimulate serotonin expression in cells of brain cortex. Bull Exp Biol Med. 2014;157(1):77-80. PMID 24909721
- Khavinson V, et al. EDR peptide: possible mechanism of gene expression and protein synthesis regulation involved in the pathogenesis of Alzheimer’s disease. Molecules. 2020;26(1):159. PMID 33396470
Research use only. Rogue Compounds products are sold strictly for laboratory research. They are not for human or veterinary use, and nothing in this article is medical advice. The studies cited here describe published research, not this product or any use of it.