Research Dossier on Vilon (Lys–Glu; KE)

(Bioregulator Peptide)

Classification & Molecular Identity

Amino acid sequence, molecular weight, structural motifs

Vilon (also transliterated in some abstracts as Vilon®/Vilonum) is a synthetic ultrashort dipeptide with the sequence Lys–Glu (KE). Analytical records list a molecular formula near C₁₁H₂₁N₃O₅ (free acid; salt forms vary) and a molecular weight in the ~275–295 g·mol⁻¹ range depending on protonation and counter-ion. Its juxtaposition of a basic residue (Lys) and an acidic residue (Glu) confers strong polarity and a net zwitterionic character at physiological pH, favoring aqueous solubility and electrostatic interactions with nucleic acids and proteins. Published research places Vilon in the family of organ-targeted “peptide bioregulators” developed by the St. Petersburg (Russia) peptide school; within that framework KE is often associated with thymus/vascular targets and compared experimentally with other 2–4-mer motifs such as KED (Vesugen), EDR (Pinealon), and AEDG (Epitalon).

Discovery history (lab, year, species)

Short peptide “bioregulators” were advanced during the late 20th century as chemically defined fragments intended to reproduce the gene-regulatory actions inferred from thymic and other tissue extracts. English-language, peer-reviewed publications describing Vilon/KE appear largely from 2010s–2020s, with mechanistic and cell-system data (thymic/vascular lineage), followed by exploratory aging-biology and neuronal models.

Endogenous vs synthetic origin

• Endogenous: Vilon (KE) is not a known circulating human hormone; it is a designed peptide whose biological inspiration stems from thymic-peptide work.

• Synthetic: All research-grade Vilon is produced via solid-phase peptide synthesis (HPLC/MS identity typically reported in methods sections). Most functional studies used H-Lys-Glu-OH at ≥95% purity.

Homologs, analogs, derivatives

• KED (Vesugen; Lys–Glu–Asp)—tripeptide with vascular endothelium focus and Ki-67 (MKI67) promoter effects.

• EDR (Pinealon; Glu–Asp–Arg)—tri-peptide prominent in antihypoxic and neuronal stress models.

• AEDG (Epitalon; Ala–Glu–Asp–Gly)—tetrapeptide with chromatin/telomere-adjacent literature in cell/invertebrate systems.
  Because these peptides were developed and assayed in parallel, English-language reviews often discuss them side-by-side to infer class vs sequence-specific effects.

Historical Development & Research Trajectory

Key milestones in discovery and study

1. Thymic lineage and immune differentiation (2011–2013). In rat thymus-derived or pineal immune cell cultures, short peptides were assessed for proliferation and differentiation effects. In one study, Vilon (KE) and Epitalon (AEDG) promoted immune-cell differentiation (toward T-helper, cytotoxic T, or B-lineage markers), whereas KED increased proliferation without altering differentiation—evidence for sequence-specific actions within the class.

2. Vascular/endothelial context (2010s). Although KED is the primary vascular tripeptide studied for MKI67activation in aged endothelium, Vilon (KE) is frequently included as a comparative agent in vascular and immune cell sets, with reports of pro-differentiation or trophic effects under defined conditions.

3. Neuro-aging models (2024). In human fibroblast-derived induced neurons (iNeurons), panels of ultrashort peptides—including Vilon/KE—reduced age-related cellular phenotypes and stimulated dendritogenesis(neurite length/branching, spine metrics) after 24–72 h exposures. These effects paralleled those of AEDG and KED, suggesting shared neurotrophic influences at the micro-peptide level.

4. Comparative stress biology (hypoxia; 2008). Rodent hypobaric hypoxia experiments ranked short peptides for antihypoxic action: EDR emerged strongest, but KE and KED were also protective, supporting stress-responseroles across the family.

5. Clinical-adjacent vascular/urologic pilots (2014–2015). In Russian-language or English-abstracted clinical reports, vasoactive tripeptides (often KED) were tested in vasculogenic erectile dysfunction and aging; KEappears in some programs as a co-agent within multipeptide courses. Methodological details are limited in English abstracts and seldom meet modern CONSORT standards.

Paradigm shifts & controversies

• From extract-like “bioregulation” to promoter-level hypotheses. The field has shifted from viewing ultrashort peptides as non-specific trophic agents to proposing direct interactions with DNA/RNA or chromatin-associated proteins, enabling gene-expression adjustments (e.g., cell-cycle, cytoprotection). For KE, the direct binding and in vivo promoter occupancy remain Not established, though class-level docking and expression data support plausibility.

• Evidence quality & generalizability. A sizable portion of the Vilon literature originates from one research lineage; independent multi-center replication with blinded methods is scarce. Claims of organ-specificity and epigenetic targeting require orthogonal validation (biophysics, genome-wide occupancy) beyond docking or correlative expression.

Evolution of scientific interest

Vilon progressed from thymic/immune differentiation models to vascular and neuro-aging paradigms (dendritic spines, induced neurons), and to exploratory clinical-adjacent use in aging programs—where mixed pro-oxidant/hematopoieticsignals have been observed for related peptides, underscoring the need for rigorous translational studies.

Mechanisms of Action

Primary and secondary receptor interactions

A single, high-affinity cell-surface receptor for Vilon has not been identified in peer-reviewed English-language sources. The following mechanistic hypotheses arise from class-level and KE-specific work:

1. Nucleic-acid binding (promoter-level micro-ligand). Reviews on peptide regulation of gene expression posit that ultrashort peptides (including KE) can recognize short consensus motifs in DNA/RNA, affecting transcription/translation and thereby tissue-specific gene programs. For KED, direct docking to the MKI67promoter correlates with Ki-67 up-regulation in aged endothelium. While KE-specific promoter docking is less developed, KE is frequently cited among the peptides with likely nucleic-acid affinity. Evidence strength: B(plausible; direct in-cell occupancy not established).

2. Immune-cell differentiation. In thymus-derived or pineal immune cell cultures, KE was reported to facilitate differentiation toward T-helper and cytotoxic T phenotypes (contrasting with KED, which mainly increased proliferation without differentiation). Evidence strength: B (replicated within class lineage; needs independent labs).

3. Neurotrophic modulation. In human iNeurons, KE (alongside AEDG/KED) stimulated dendritogenesis and mitigated age-related cell signatures over 24–72 h exposures—consistent with synaptic and cytoskeletal gene-network effects. Evidence strength: B (cellular; mechanistic nodes not fully mapped).

Intracellular signaling pathways

• Cell-cycle & proliferation (immune and endothelial systems): downstream of promoter-level hypotheses, KE may up-shift expression of cyclins/Ki-67 in target contexts (direct evidence for KED > KE; for KE it is mainly inferred).

• Differentiation signaling (immune cells): data suggest promotion of phenotypic maturation (surface markers) rather than global mitogenesis—distinct from KED.

• Neuronal plasticity: increases in dendritic spine metrics imply effects on actin remodeling, CaMKII/CREB-like pathways, or synaptic scaffolds (e.g., PSD-95), but these KE-specific nodes have not been fully delineated.

CNS vs peripheral effects

• Peripheral: The thymic/immune and vascular contexts remain central for KE (differentiation, endothelial trophic support).

• CNS: Emerging evidence in human induced neurons and AD-adjacent spine paradigms suggests neurotrophicpotential; in vivo CNS pharmacology for KE is minimal relative to in vitro studies.

Hormonal, metabolic, immune interactions

KE has no known classical endocrine receptor. Immune-cell data indicate phenotype (differentiation) effects more than large cytokine surges, but comprehensive cytokine profiling under KE exposure remains limited.

Evidence grading (mechanism)

• A: KE repeatedly influences immune-cell differentiation in thymic/pineal immune cell sets (peer-reviewed lineage).

• B: KE promotes dendritogenesis/spine integrity in iNeurons and is frequently implicated in gene-expressionmodulation (class-level).

• C: Primary binding target(s), biophysical affinities, and in vivo promoter occupancy are not established.

Pharmacokinetics & Stability

ADME profile (current knowledge)

Peer-reviewed English-language literature does not report a validated human PK profile for KE. Class-based expectations for 2-mer peptides are:

• Absorption: Parenteral administration—rapid systemic exposure; oral bioavailability expected low (unless protected/modified). Intranasal delivery has not been systematically studied for KE. Status: Not established.

• Distribution: Likely extracellular distribution with rapid renal filtration; cellular uptake via endocytosis or transporters is plausible but unquantified. Status: Not established.

• Metabolism: Peptidases degrade KE to amino acids; plasma half-life typically minutes to tens of minutes for free dipeptides. Status: Not established for KE.

• Elimination: Predominantly renal; specific human clearance/t½ data not available. Status: Not established.

Stability

In vitro, KE remains active over typical incubation periods (hours). In vivo stability is unknown; chemical modification (e.g., N-acylation, D-residues) could in principle extend t½, but KE studies largely use the native dipeptide.

Storage/reconstitution considerations

Suppliers recommend dry, −20 °C storage; solution stability depends on buffer and microbial control. No peer-reviewed CMC monograph specific to KE is available.

Preclinical Evidence

Immune differentiation (thymus/pineal immune cells)

• Linkova et al.: In pineal immune-cell cultures, KE (Vilon) and AEDG drove differentiation (markers for T-helper, cytotoxic T, and B-cells), whereas KED predominantly enhanced proliferation with minimal differentiation—suggesting complementary roles across peptides. Investigational concentrations: low-to-mid micromolar (24–72 h) typical for these assays.

Endothelium/vasculature

• Comparative sets with KED: Although the strongest endothelial Ki-67 activation data exist for KED, KE is commonly included as a control/comparator in vascular cell panels and appears to exert trophic effects in aged endothelium, albeit less consistently than KED in MKI67-specific assays.

Hypoxia stress (rodent)

• Kozina et al.: In a hypobaric hypoxia model, peptide mini-panel (EDR, KED, KE, AEDG) demonstrated antihypoxic action; ranking differed by endpoint, with EDR often highest. The result positions KE within a stress-resilience family but does not isolate a unique KE mechanism. Investigational dosing used in study: peptide injections per rodent protocol (see methods).

Neuronal aging & dendritogenesis (human iNeurons)

• Kraskovskaya et al. 2024: Short peptides (AEDG, KED, KE, among others) in human induced neuronsattenuated several age-related cellular phenotypes and enhanced dendritic arborization after 24–72 h exposure, supporting a neurotrophic signal for KE within the class. Investigational concentrations: low-to-mid µM; precise values reported in methods.

Dose ranges tested (illustrative; all investigational)

• Cell systems: 1–50 µM, 24–72 h (immune differentiation; endothelial or neuronal endpoints).

• Rodent stress: injection schedules defined in each experiment; species scaling to humans is not appropriatewithout PK.

Comparative efficacy/safety

• Efficacy: KE promotes immune-cell differentiation; provides trophic effects in endothelium; supports dendritogenesis in iNeurons; antihypoxic protection observed but less pronounced than EDR in some settings.

• Safety: No overt cellular or acute rodent toxicity is reported at research exposures; however, human pilot courses with related peptides have yielded mixed PD (e.g., pro-oxidant chemiluminescence; hematopoietic changes) that must be investigated under rigorous trial conditions.

Limitations

• KE-specific molecular targets remain unidentified;

• PK/PD unknown; connecting dose–exposure–response is not currently possible;

• Many results are concentrated in a single research lineage, underscoring the need for independent replication.

Human Clinical Evidence

Orientation: Published, indexed human studies specifically administering Vilon (KE) are sparse and often non-randomized, with limited methodology in English. Where available, we summarize cautiously. Many “clinical-adjacent” programs in aging or vasculogenic conditions report courses that combine KE with other short peptides; attribution to KE alone is therefore uncertain.

Aging/“geroprevention” (open-label composite programs)

• Meshchaninov et al., 2015 (n = 32): A peptide program in middle-aged/elderly volunteers used Pinealon and Vesugen (not KE alone) and reported improvements in composite biological-age indices but accompanied by pro-oxidant chemiluminescence and decreased CD34⁺ cells. KE was not the sole agent; nonetheless, these mixed PDsignals frame the safety questions that any KE-only trial should pre-specify. Investigational course details: not fully specified in English abstract. Evidence grade: C (small, uncontrolled, mixed signals).

Vascular/urologic microcirculation

• Kitachev et al., 2014 (English abstract): A vasoactive tripeptide (most often KED) was tested in atherosclerotic vasculogenic ED; KE appears in the same research toolkit but was not isolated as a single agent in the abstracted protocol. Evidence grade: C (methodological limitations in abstract).

Immunology/pineal immune cells (preclinical-to-clinical bridge)

• While thymus and pineal immune-cell differentiation effects for KE are replicated in vitro, controlled human immunologic trials (e.g., vaccine-adjuvant tests) have not been published in indexed English-language journals specific to KE. Status: Not established.

Summary of clinical evidence. There are no large, randomized, placebo-controlled trials of Vilon (KE) with prespecified primary clinical endpoints in the indexed English literature. Observational or open-label reports, often combining peptides, are hypothesis-generating only. Robust human efficacy and safety for KE alone therefore remain Not established.

Comparative Context

Related peptides and why they matter methodologically

• KED (Vesugen)—best endothelial mechanistic evidence (MKI67 promoter; Ki-67 recovery in aged cells); useful as a vascular positive control.

• AEDG (Epitalon)—chromatin/telomere literature; often included for neuronal and anti-stress comparisons.

• EDR (Pinealon)—strongest antihypoxic signals in some rodent work; neurocentric.

• Using this panel side-by-side with KE is valuable to distinguish class from sequence-specific effects.

Advantages (research perspective)

• Defined 2-mer with straightforward synthesis and QC;

• Evidence for immune-cell differentiation (vs pure proliferation);

• Neurotrophic readouts (dendrites/spines) in human iNeurons;

• Integrates into mechanistic designs (omics, promoter occupancy, micro-biophysics).

Disadvantages/constraints

• No PK, no primary target, no in vivo occupancy;

• Clinical evidence limited/heterogeneous;

• Safety/hematopoietic findings from class-adjacent pilots warrant dedicated monitoring.

Research category placement

Vilon (KE) fits as a mechanistic tool for immune differentiation, endothelial aging, and neuronal plasticityexperiments, and as a comparator within short-peptide panels.

Research Highlights

• Identity: ultrashort dipeptide Lys–Glu (KE); Mr ~275–295 g·mol⁻¹ (salt/protonation dependent).

• Immune differentiation: KE promotes thymus/pineal immune-cell differentiation (vs KED, which mainly drives proliferation).

• Vascular endothelium: KE appears trophic in aging endothelium; strongest MKI67 promoter activation data are for KED, with KE often used as a comparator.

• Antihypoxic stress: KE shows protective effects in hypobaric models (ranked below EDR in some endpoints).

• Neuronal aging: KE stimulates dendritogenesis and mitigates age-associated features in human iNeurons (24–72 h exposures).

• Clinical-adjacent: Open-label aging programs combining peptides report mixed PD (putative benefits alongside pro-oxidant and hematopoietic changes); KE-only controlled trials are not available.

Conflicting/uncertain evidence.

• Primary molecular target(s) and in vivo promoter occupancy for KE are unknown;

• Human PK, dosing, and safety are not established;

• Efficacy claims rely on limited and non-randomized studies, often multi-peptide.

Potential Research Applications (no clinical claims; research-use framing)

1. Thymic/immune differentiation assays

   • Use primary human thymic cultures or PBMC subsets to quantify KE-induced lineage commitment(surface markers, cytokine profiles) vs KED/AEDG/EDR; incorporate single-cell RNA-seq to map KE-specific differentiation trajectories.

2. Vascular aging & cell-cycle rescue

   • In senescent endothelial cultures, pair time-resolved RNA-seq/ATAC-seq with Ki-67/PCNA IHC and EdUlabeling to determine whether KE directly re-primes cell-cycle—contrasted with KED to parse differentiation vs proliferation niches.

3. Neuro-aging plasticity

   • In human iNeurons and brain organoids, quantify KE effects on dendritic arborization, spine density, and synaptic gene modules; test under oxidative/ischemia-mimetic stress conditions.

4. Biophysical target validation

   • Establish binding constants (SPR/ITC) for KE–DNA/RNA candidates (e.g., promoters of differentiation/cell-cycle genes). Use photo-crosslinkable KE analogs to perform peptide-ChIP and chemoproteomics in cells—key to moving beyond docking.

5. Exploratory PK

   • Develop LC-MS/MS methods for KE quantitation; perform rodent PK with parenteral dosing to derive t½, Vz, and clearance; evaluate stabilized analogs or nanoformulations for improved exposure.

6. Safety biomarkers

   • In preclinical/phase-0 settings, include oxidative (e.g., 8-iso-PGF₂α, GSH/GSSG) and hematopoietic (e.g., CD34⁺) panels—given mixed signals in class-adjacent human pilots.

Safety & Toxicology

Preclinical and translational hints

• In vitro and small animal experiments report no acute toxicity for KE at research exposures.

• Human: There are no KE-specific randomized safety trials. Aging programs combining multiple short peptides (not KE alone) reported pro-oxidant chemiluminescence and reduced CD34⁺ cells—an ambiguous finding requiring controlled evaluation before any broad translational claims.

Known/theoretical molecular risks

• Off-target gene regulation if KE binds nucleic acids promiscuously;

• Unintended proliferation if cell-cycle re-entry is triggered in undesirable contexts (e.g., neointimal hyperplasia). These risks are theoretical pending target mapping.

Data gaps

• Human PK, exposure–response, dose rationale;

• GLP toxicology (repeat-dose, genotoxicity, reproductive, carcinogenicity);

• KE-only randomized, placebo-controlled trials with safety and omics correlates.

Limitations & Controversies

• Evidence concentration: A large fraction of KE data comes from one research lineage; independent labs are needed for external validity.

• Mechanistic proof: Current support for epigenetic/promoter action is largely in silico or correlative; in-cell occupancy and direct targets remain unknown.

• Clinical translation: Human evidence is limited and heterogeneous (small open-label programs, multi-peptide courses). Strong claims exceed the peer-reviewed evidence base and should be avoided.

Future Directions

1. Ortho-validation of targets (biophysics + in-cell occupancy) to move KE from correlative to causal gene-regulator status.

2. PK platform for KE and stabilized analogs (D-residues, N-acyl caps, peptide–lipid conjugates) to overcome short half-life.

3. Mechanistic RCTs (phase-0/IIa) in carefully defined vascular-aging or immune-differentiation settings with omics endpoints, blinding, randomization, and independent adjudication.

4. Comparative peptide mapping (KE vs KED/EDR/AEDG) in the same assay cascades to disentangle sequence-specificity from class effects.

5. Safety emphasis (oxidative and hematopoietic panels) given mixed PD in aging pilots.

References

1. Khavinson V, et al. Peptide Regulation of Gene Expression: A Systematic Review. Int J Mol Sci. 2021;22: (PMCID: PMC8619776). (Class-level DNA/RNA interaction framework; includes KE/EDR/AEDG/KED.)

2. Linkova NS, et al. Peptidergic stimulation of differentiation of immune cells derived from the pineal gland. Bull Exp Biol Med. 2011;151(1):60-63. (PMID: 22803057). (KE promoted differentiation; KED mainly proliferation.)

3. Kozina LS, et al. Investigation of antihypoxic properties of short peptides. Ross Fiziol Zh Im I M Sechenova.2008;94(6):639-648. (PMID: 18546825). (KE protective in hypobaric hypoxia among peptide panel.)

4. Kraskovskaya N, et al. Short Peptides Protect Fibroblast-Derived Induced Neurons from Aging and Stimulate Dendritogenesis. Int J Mol Sci. 2024;25:11363. (PMCID: PMC11546785). (KE among peptides enhancing dendrite metrics in human iNeurons.)

5. Meshchaninov VN, et al. Cellular and metabolic part of geroprophylactic effects of peptides… Adv Gerontol.2015;28(3): (PMID: 26390612). (Open-label aging program; mixed pro-oxidant/hematopoietic PD in multi-peptide courses.)

6. Kitachev KV, et al. Vasoactive tripeptide therapy (Vezugen) in atherosclerotic vasculogenic erectile dysfunction.Adv Gerontol. 2014;27(1): (PMID: 25051774). (Clinical-adjacent vascular context; KE cited within peptide toolkit.)

Notes on investigational exposures where reported:
• Immune/neuronal cell systems: KE typically 1–50 µM, 24–72 h; exact concentrations in each study’s methods.
• Rodent hypoxia: peptide injections per protocol; numeric human extrapolation is inappropriate.

⚠️ Disclaimer This peptide is intended strictly for laboratory research use. It is not FDA-approved or authorized for human use, consumption, or therapeutic application.