Pinealon: brain-protective peptide (Glu-Asp-Arg / EAR)
A synthetic three-amino-acid peptide studied in animals for protecting brain cells from damage due to low oxygen; experimental, not an approved drug.
A researcher, an agent, or an algorithm wrote down the sequence and picked a target to hit.
An AI model like OpenFold3 or AlphaFold built a 3D structure and scored how well it fits the binding site.
A second contributor repeated the computation on their own hardware and the scores matched.
A chemistry service or a researcher ordered the sequence, it was manufactured, and mass spectrometry confirmed the right molecule was produced.
A binding or activity measurement confirmed that it actually does what the computer predicted — or didn't.
Snapshot
Class: Synthetic neuroprotective tripeptide (Khavinson bioregulator)
Evidence tier: Animal-only evidence
Status: Not approved by FDA, EMA, MHRA, Health Canada, or TGA; classified as a research chemical in the United States
Best-supported effect: Suppression of reactive oxygen species and protection against necrotic cell death in cultured neurons (in vitro); attenuated hypoxic and ischemic behavioral deficits in aged rodent models (animal)
Main caveat: All published efficacy data originates from a single Russian research program (Khavinson group); no independent Western replication; no controlled human efficacy trials; one small uncontrolled Russian clinical study does not establish human efficacy
What this is
Pinealon is a synthetic tripeptide with the sequence glutamate–aspartate–arginine (Glu-Asp-Arg; single-letter code EDR). It was developed by Vladimir Khavinson and colleagues at the St. Petersburg Institute of Bioregulation and Gerontology as part of a broader program of short "bioregulator" peptides hypothesized to modulate tissue-specific gene expression and restore age-related functional decline. Pinealon is positioned as the brain-tissue entry in the Khavinson lineup — conceived as a pineal-gland-derived neuroprotective agent — in contrast to the related tetrapeptide Epithalon, which targets pineal endocrine function. The published preclinical and clinical-adjacent record for Pinealon is concentrated almost entirely within the originating research program and a small set of affiliated Russian collaborators, with no independent Western replication under modern trial-methodology standards.
Evidence map
| Evidence layer | Grade | What it supports |
|---|---|---|
| Human | Weak / anecdotal | One small uncontrolled Russian clinical study in truck drivers reported reduced neurotic disorder markers; no controlled human efficacy trial exists; no human pharmacokinetic data |
| Animal | Moderate | Rodent studies report attenuation of hypoxic behavioral deficits and improved neurological outcomes after carotid occlusion; findings concentrated in one research program |
| In vitro | Moderate | Cultured neuron studies show ROS suppression and protection against necrotic cell death; ion-interaction work with DNA segments published; all from originating or affiliated groups |
| Computational | None | No computational or structural prediction data identified |
| Mechanism | Plausible (contested) | Proposed cell-membrane penetration and direct DNA-regulatory-region interaction to modulate gene expression; proposed upregulation of anti-apoptotic genes and neurotrophic factors; this mechanistic claim is contested in Western literature and has not been independently confirmed |
A large share of the published evidence originates from one research program (Khavinson group, St. Petersburg); independent replication depth is the defining limitation of this evidence base.
Claim check
| Claim | Verdict | Evidence layer | Confidence |
|---|---|---|---|
| Neuroprotection against oxidative stress and ischemic insult | Supported (animal / in vitro) | Animal + in vitro | Medium — single research program; no independent replication |
| Cognitive enhancement in healthy individuals | Not established | Animal | Low — rodent behavioral improvements after ischemia do not establish cognitive enhancement in healthy humans |
| Useful for age-related cognitive decline or neurodegeneration | Weak (preclinical) | Animal | Low — extrapolation from rodent aging models; no clinical trial in dementia or MCI populations |
| Melatonin regulation and pineal-axis support | Not established | None | Low — theoretical framing based on peptide origin; no direct human or animal melatonin-endpoint study extracted in this card |
| Blood-brain barrier penetration at clinically relevant doses | Partially supported (theoretical / in vitro) | In vitro | Low — size and charge characteristics support theoretical penetration; no human pharmacokinetic confirmation |
| Russian dietary-complex registration equals drug approval | Contradicted | None | High — Russian Khavinson-affiliated capsule products are marketed as dietary peptide complexes, not registered pharmaceuticals; this is not equivalent to EMA, FDA, MHRA, or other Western regulatory approval |
Experimental exposure
This section reports exposure used in animal experiments and the one available human-adjacent clinical study. It does not establish human dosing.
| Context | System | Experimental exposure | Duration | Endpoint | Limitation |
|---|---|---|---|---|---|
| Animal experiment — hypoxia model | Aged rats | Dose not individually extracted; Khavinson-group study design | Acute / short course | Behavioral recovery markers, cytokine / caspase-3 levels in brain | Rodent model; no human translation established; single research program |
| Animal experiment — carotid occlusion | Rats | Dose not individually extracted; study-specific | Acute / short course | Neurological and behavioral outcomes post-ischemia | Stroke-adjacent research; no human translation established |
| Animal experiment — prenatal hyperhomocysteinemia | Rat offspring | Dose not individually extracted | Prenatal / early postnatal | Offspring neuroprotection markers | Specialized developmental model; no human equivalence |
| Human-adjacent clinical study (uncontrolled) | Russian truck drivers; n not individually extracted from source | Peptide complex; exact regimen not individually extracted | Not individually extracted | Neurotic disorder markers | Uncontrolled study; small sample; Russian-only; no blinded comparator; insufficient for human efficacy claim |
Preclinical safety signals
| Signal | System | Notes |
|---|---|---|
| No major toxicity reported in reviewed preclinical studies | Rodent models | Studies are short-duration and single-lab; long-term or chronic-exposure toxicology not individually extracted |
| Injection-site infection risk (research-chemical supply) | Context — research-chemical sourcing only | Lyophilized research-chemical supply introduces sterility and quality uncertainty absent from clinic-supplied materials; this is not a pharmacological signal from the compound itself |
| Long-term safety — repeated courses | Not established | Cumulative effects of repeated Khavinson-style courses across years have not been independently studied |
| CNS malignancy concern (theoretical) | Class concern | Source notes that agents that stimulate neurogenesis or modulate CNS gene expression raise theoretical tumor-promotion concern in patients with subclinical or remote-history CNS malignancy; no direct toxicological finding for Pinealon |
| Seizure threshold effects | Not studied | Source notes neuromodulatory short peptides have not been adequately evaluated for seizure-threshold effects |
| Reproductive / developmental safety | No data | Reproductive toxicology data are absent; source notes no adequate data for pregnancy or breastfeeding contexts |
No human adverse event data from controlled studies are identified. Safety context is derived from source-bundle descriptions of limited community adoption and single-program preclinical work.
Regulatory status
| Region / body | Status | Notes |
|---|---|---|
| US (FDA) | Not approved | Classified as a research chemical; not a recognized dietary supplement ingredient; not on the FDA list of peptides eligible for 503A compounding; injectable forms sold through research-chemical supply channels not authorized for human use |
| EU (EMA) | Not approved | Source confirms no EMA approval |
| UK (MHRA) | Not approved | Source confirms no MHRA approval |
| Canada (Health Canada) | Not approved | Source confirms no Health Canada approval |
| Australia (TGA) | Not approved | Source confirms no TGA approval |
| Russia | No pharmaceutical-equivalent approval | Russian Khavinson-affiliated capsule and sublingual products are marketed as dietary peptide complexes, not as registered pharmaceuticals; this is a different regulatory category with lower evidence requirements; not equivalent to Western drug approval |
| WADA | Status uncertain — per available sources concern | Not specifically named on the WADA Prohibited List per source; source notes the WADA S0 catch-all category (substances not approved for therapeutic use) may apply to injectable forms; per available sources status; current list status not independently refreshed in this card |
Mechanism
Pinealon (Glu-Asp-Arg) is proposed by the Khavinson group to act through direct cell-membrane penetration and interaction with DNA regulatory regions, modulating gene expression in neuronal and pineal tissue. Proposed downstream effects include upregulation of anti-apoptotic genes, increased expression of neurotrophic factors, suppression of reactive oxygen species, and reduced necrotic cell death under oxidative or ischemic stress conditions. Source materials also describe putative influence on pinealocyte function and melatonin synthesis through epigenetic mechanisms.
Target confidence: Predicted / contested. The mechanism of direct DNA-regulatory-region interaction by a tripeptide is contested in Western literature and has not been independently confirmed outside the originating research program. The primary molecular target has not been validated through independent receptor binding or pathway studies. Source-published in vitro work demonstrates ROS suppression and cell-viability effects, but the intracellular pathway linking tripeptide exposure to these outcomes is not independently established.
The most specific mechanistic support points to oxidative-stress protection and neuronal survival under ischemic insult — a narrower framing than the broader "cognitive enhancement" or "gene regulation" language used in marketing contexts.
Chemistry
| Field | Value |
|---|---|
| Sequence | Glu-Asp-Arg (EDR) |
| Length | 3 amino acids |
| Topology | Linear |
| Molecular weight | 418.4 Da |
| Formula | C₁₅H₂₆N₆O₈ |
| CAS | 289656-45-7 |
| Plasma half-life | Minutes (reported); claimed prolonged CNS effects are not quantified in independent studies |
| Sequence confidence | Verified (consistent across source sections) |
| Modifications | None described; natural L-amino acid residues |
| Salt form | Not specified in source |
Open questions
- Independent replication: The core neuroprotection, cell-viability, and clinical-adjacent findings have not been reproduced by Western laboratories under modern trial-methodology standards. Independent replication is the primary unresolved question for the entire evidence base.
- Human pharmacokinetics: Absorption (particularly oral and sublingual bioavailability of the intact tripeptide), distribution, blood-brain-barrier penetration at clinically relevant concentrations, and clearance have not been characterized in independent human pharmacokinetic studies. The Khavinson group's claim of intact peptide absorption is not anchored to Western-standard pharmacokinetic confirmation.
- Controlled human efficacy trials: No blinded randomized controlled trial in humans exists for any cognitive, neuroprotective, or longevity endpoint. The one available human-adjacent study is uncontrolled, small, and Russian-only.
- Mechanism specificity: Direct DNA-regulatory-region interaction by a tripeptide is contested in Western structural biology. The molecular target and intracellular pathway have not been independently confirmed.
- Long-term safety: Chronic exposure data from repeated Khavinson-style treatment courses across years are absent. Theoretical class concerns about neurogenesis-stimulating agents in CNS-tumor contexts have not been addressed by dedicated safety studies.
- Seizure-threshold effects: No adequate evaluation of Pinealon's effects on seizure threshold has been published outside the originating program.
- Single-program evidence depth: A large share of published evidence derives from one research network. Whether the preclinical and clinical-adjacent findings generalize beyond this network remains unknown.
Research directions for this peptide, selected from the current sources — hypotheses you can explore and model. None of it is proven yet; tap any one to see the full thinking.
Does Pinealon only work when brain cells die from an ion imbalance, rather than from the protein clumps seen in Alzheimer's?
If true, researchers could quickly rule out Pinealon for Alzheimer's trials and focus instead on stroke or traumatic brain injury, saving years of misdirected clinical effort and pointing to which patients might actually benefit.
Does this peptide work in all brain areas, or only in the part of the brain where it has been tested so far?
Knowing which brain regions respond could prevent wasted clinical trials in the wrong disease and instead direct development toward conditions like cerebellar stroke or certain balance disorders where it might genuinely help patients.
Does this three-amino-acid peptide work by activating the brain's built-in stress-defense genes rather than by neutralizing damage directly?
If true, Pinealon could be the seed for a class of very small gene-activating molecules that help aging or injured neurons defend themselves. This could matter for people with neurodegenerative diseases where the brain's own defenses are failing.
If scientists slightly rearrange the structure of this three-amino-acid peptide so it forms a closed loop, would it last longer in the body while still protecting brain cells?
A longer-lasting version of Pinealon could be tested meaningfully in humans for the first time, potentially offering a very small, inexpensive molecule to help protect brains after stroke or in aging, which current drugs do poorly.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.8686137199401855 | openfold3-mlx |
| ranking score | 0.9128403663635254 | openfold3-mlx |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.394 | global PDE — lower = better |
| disorder | 0.084 | fraction disordered |
| chain pair ipTM (A, B) | 0.869 | interface quality |
▸3-letter notation
▸recipeopenfold3-mlx 0.3.1
| parameter | value |
|---|---|
| model | openfold3-mlx 0.3.1 |
| weights | — |
| hardware | — |
| mlx version | — |
| python | — |
| random seed | — |
| msa strategy | — |
| diffusion samples | 1 |
| runtime | 75s |
| predicted by | mlx@peptide |
| predicted at | 2026-05-03 |
▸citationbibtex
@peptide{pep10932,
sequence = {EAR},
target = {neuroprotective},
author = {peptidemodel},
year = {2026},
status = {computed}
}