Pinealon

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Pinealon · EDR peptide · T-33 peptide · glutamylaspartylarginine

Glu (147.13) + Asp (133.10) + Arg (174.20) sum to 454.43 as free amino acids. Removing two waters for the two peptide bonds gives 418.40, and element counts resolve to C15H26N6O8.

This is the practical detail most vendor pages omit. Dissolution is not instantaneous — reported protocols call for warming to 37 °C and ultrasonic agitation. A vial that appears not to dissolve on first attempt is behaving as expected.

Pinealon shares its carbon, hydrogen and nitrogen counts with the AHK tripeptide used in copper peptides: C15H26N6O8 versus C15H26N6O4. The two differ only by four oxygens, placing them exactly 64 Da apart at 418.40 and 354.40. They are readily distinguished by mass, but the shared C/H/N composition is worth knowing if both are handled in the same workflow.

Pinealon is one of a set of ultra-short peptide bioregulators developed by Vladimir Khavinson and colleagues at the St Petersburg Institute of Bioregulation and Gerontology. The family shares a design logic rather than a single target.

Two to four residues, built from acidic and basic amino acids Small enough and appropriately charged to cross both the plasma membrane and the nuclear envelope Proposed to act on DNA directly rather than through a cell-surface receptor Each member associated with a tissue or organ system

Related members encountered in the same catalogues Epitalon (Ala-Glu-Asp-Gly) · Vilon · Livagen · Cortagen · Cardiogen · Chonluten · Vesugen · Cartalax · Bronchogen · Thymalin · Prostamax · Ovagen · Pancragen · Testagen · Crystagen · Vesilute · Thymagen

Pinealon and Epitalon, the two best-known members, both carry the Glu-Asp core, which is characteristic of the acidic bioregulators.

EDR is described as derived from Cortexin, a crude polypeptide extract of brain cortex. Cortexin appears repeatedly in this literature as the comparator preparation, and the distinction matters — Pinealon is a single defined tripeptide, Cortexin is an undefined mixture.

The claim that separates Pinealon from most peptides in a catalogue is that it does not act at a receptor.

Pinealon does not appear to bind cell-surface or cytoplasmic receptors. Work with fluorescence-labelled short peptides in HeLa cells reported penetration of both the plasma membrane and the nuclear membrane, with sequence-specific interaction with deoxyribooligonucleotides and DNA in vitro.

(Fedoreyeva et al., Biochemistry Moscow, 2011)

The proposed consequence is epigenetic: site-specific peptide-DNA binding modulating transcription, rather than signal transduction from a receptor. This is a mechanistic claim about gene regulation and should be read as such — it is the framework the Khavinson literature works within, not a settled consensus position.

The best-characterized experimental findings. In rat cerebellar granule cells:

Pinealon at 10, 50 and 100 nM for 30 minutes dose-dependently prevented the rise in reactive oxygen species induced by ouabain Pinealon at 10 nM suppressed ERK 1/2 activation in cells exposed to homocysteine Reported reduction in necrotic cell death by propidium iodide staining, accompanied by delayed ERK 1/2 activation (Khavinson et al., Rejuvenation Research, 2011)

The framing is that ROS act as second messengers in MAPK/ERK signalling, so lowering ROS attenuates pathway activation and reduces apoptotic signalling.

Homocysteine exposure is used as the stressor because it activates NMDA receptors, driving calcium influx and ROS production. Pinealon is reported to raise resistance to hypoxic stress and reduce NMDA excitotoxic potential via endogenous antioxidant enzyme systems.

Reported activation of SOD2 and GPX1.

A specific and testable proposal: Pinealon is reported to bind the promoter region of the tryptophan hydroxylase gene, increasing TPH expression and therefore serotonin synthesis. Molecular docking reported more negative binding energy for Pinealon against DNA than for comparator bioregulators, with an approximately 1.9-fold increase in serotonin synthesis reported in younger cell cultures.

(Khavinson et al., Bulletin of Experimental Biology and Medicine, 2014)

Reported modulation of caspase-3 and p53, and normalization of IL-6 and TNF-α in models of acute hypoxic hypoxia in old rats. The reported contrast with Cortexin is the interesting part: Cortexin lowered cell death but left IL-6 elevated, while Pinealon returned the markers toward baseline.

(Mendzheritskii et al., Advances in Gerontology, 2014)

Reported preservation of dendritic spines and reduced neuronal apoptosis, with the gene-expression framework set out in the Molecules review.

(Khavinson et al., Molecules, 2021)

Reported alteration of irisin expression in muscle cells, with irisin discussed in relation to telomere length.

(Khavinson et al., Bulletin of Experimental Biology and Medicine, 2016)

These are largely Russian-language studies in gerontology journals with small samples and limited independent replication. Reported at face value below.

Pinealon at 50, 100 and 200 ng/kg by injection for 5 days showed a dose-dependent effect on maintenance of a previously acquired skill.

(Karantysh et al., Neurochemical Journal, 2020)

Pinealon at 10 µg/kg daily for 5 days protected offspring, with reported improvement in cognitive function and reductions in oxidative stress and neuronal necrosis.

(Arutjunyan et al., Int J Clin Exp Med, 2012)

Reported promotion of cell proliferation and blocking of apoptosis in dermal and epidermal cells from both young and old rats.

(Voicekhovskaya et al., Bull Exp Biol Med, 2012)

A study in professional lorry drivers reported improved resistance to work-related stress and reduced incidence of borderline mental disorders.

(Bashkireva & Artamonova, Advances in Gerontology, 2012)

In patients aged 41 to 83 with chronic polymorbidity, reported anabolic and neuroprotective effects with slowed aging indicators, and no change in chromatin condensation — offered as evidence of genetic safety. The same study reported Vesugen as showing stronger geroprotective effect than Pinealon.

(Meshchaninov et al., Advances in Gerontology, 2015)

Pinealon is not approved by the FDA for any indication, and is not approved as a drug or dietary supplement. The evidence base is predominantly in vitro and animal work, with a small number of Russian-language clinical reports that have not been independently replicated.

Material supplied for laboratory use is a research chemical. It is not a drug, food, cosmetic, or dietary supplement, has not been evaluated by the FDA, and is not intended for human or veterinary use.