Stemokin

Stemokin (Ile-Glu-Trp) is a synthetic tripeptide pharmaceutical composed of the amino acids isoleucine, glutamic acid, and tryptophan that functions as a potent hematopoietic stem cell stimulator and immunomodulator. Registered in Russia as a prescription medication, Stemokin has gained attention among biohackers, longevity enthusiasts, and individuals seeking immune system support due to its unique ability to act on early-stage hematopoiesis at the CD34+ stem cell level—comparable to colony-stimulating factors like G-CSF and GM-CSF. Typical dosing in research settings ranges from 1–100 µg administered subcutaneously, with treatment protocols spanning 14–42 days depending on the therapeutic objective.

What Is Stemokin?

Stemokin, chemically designated as L-Isoleucyl-L-Glutamyl-L-Tryptophan (IEW), is a fully synthetic tripeptide derived from structure-activity relationship (SAR) studies of the thymus-derived dipeptide Glu-Trp (Thymogen). The peptide was developed at the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry at the Russian Academy of Sciences and is commercially produced by Immunotech Developments Inc. in Canada.

What distinguishes Stemokin from other immunomodulating peptides is its mechanism of action. Unlike peptide immunomodulators such as Thymosin alpha-1 (Zadaxin), Immunox, or Thymogen that primarily affect mature immune cells, Stemokin acts on earlier stages of hematopoiesis, directly stimulating the proliferation of CD34+ hematopoietic stem cells. Pharmacokinetic studies using radiolabeled H3-(Ile-Glu-Trp) demonstrated that intramuscularly administered Stemokin predominantly accumulates in bone marrow (approximately 45%), confirming its targeted action on hematopoietic tissue.

The primary human-use benefits attributed to Stemokin include:

 
• Stimulation of hematopoietic stem cell proliferation
 
• Restoration of bone marrow function following radiation or cytostatic damage
 
• Balanced Th1/Th2 immune response modulation
 
• Potential vaccine adjuvant properties
 
• Accelerated recovery of blood cell populations

How It Works

Hematopoietic Stem Cell Stimulation

Stemokin's primary mechanism involves direct stimulation of colony-forming unit-spleen (CFU-S) cells, the earliest committed hematopoietic progenitors. Research demonstrates that Stemokin stimulates the exogenous bone marrow colony restoration after irradiation at doses of 1 Gy and 4 Gy, outperforming its parent compound Thymogen which only showed efficacy at 1 Gy.

In comparative studies against granulocyte colony-stimulating factor (G-CSF), Stemokin demonstrated superior bone marrow restoration. By day 14 after 7 Gy irradiation, the CFU pool volume increased by 2.5 times in Stemokin-treated subjects. By day 21, bone marrow cellularity in the Stemokin group was completely restored—recovering twice as intensively as the G-CSF treatment group.

Immune Response Modulation

Stemokin exhibits immunomodulatory properties through its influence on T-helper cell balance. Unlike aluminum-based adjuvants (Alhydrogel) that predominantly stimulate Th2 responses, Stemokin promotes a balanced Th1/Th2 immune response.

In murine vaccination models using the VAXIGRIP® influenza vaccine, Stemokin-treated groups demonstrated enhanced IgG2a antibody responses (indicative of Th1 activation) while maintaining adequate IgG1 levels (Th2 marker). This balanced response appeared two weeks earlier than in aluminum adjuvant groups, suggesting Stemokin promotes more rapid protective immunity.

Bone Marrow Accumulation

The peptide's efficacy is partly attributed to its preferential tissue distribution. Pharmacokinetic analysis revealed that following intramuscular administration, approximately 45% of the administered dose accumulates in bone marrow tissue, ensuring high local concentrations at the site of hematopoietic activity.

Dosage Protocols

Research protocols have employed varying Stemokin doses depending on the therapeutic objective:

Low dose: 1 µg per administration—demonstrated measurable immunomodulatory effects in murine models

Moderate dose: 25 µg per administration—showed intermediate hemostimulating activity

High dose: 100 µg per administration—produced the most pronounced IgG2a enhancement and balanced Th1/Th2 response

In toxicological studies, doses up to 10,000 µg/kg showed no toxic effects in mice after single parenteral injection. The recommended potential human therapeutic dose extrapolated from animal studies is approximately 10–100 µg/kg, providing a safety margin of 10–1000 times below the no-observed-adverse-effect level.

Cycling considerations: Research protocols typically employ administration on Day 1 followed by a second dose on Day 28, with blood collection and assessment at days 14, 28, and 42 to monitor immune response development.

How to Use

Stemokin is administered via subcutaneous injection. In research settings, the peptide is prepared as follows:

Stock solutions are prepared at concentrations of 20 mg/mL or 0.5 mg/mL in sterile, non-pyrogenic saline. Solutions are filtered through sterile, non-pyrogenic PVDF membrane filters with porosity not more than 0.2 μm. The prepared solution is administered as a bolus subcutaneous injection, typically in volumes of 100 µL per dose.

The peptide is supplied as Stemokin Sodium (L-Isoleucyl-L-Glutamyl-L-Tryptophan Monosodium salt) with pharmaceutical-grade purity of 99.8% as verified by LCMS UPLC analysis.

Results Timelines

Based on published research data:

Week 2 (Day 14): Initial immune response markers become detectable; early antibody production begins

Week 4 (Day 28): Significant differences in IgG2a levels become apparent between Stemokin and control groups; bone marrow restoration measurable in radiation-damaged models

Week 6 (Day 42): Peak immune response achieved; IgG2a concentrations in Stemokin groups significantly exceed aluminum adjuvant groups; complete bone marrow cellularity restoration in hemostimulation protocols

In radiation recovery models (7 Gy exposure), peripheral blood and initial hematopoietic compartments showed recovery by day 14, with complete CFU pool restoration by day 21.

Research Evidence

The scientific literature supporting Stemokin's biological activity includes:

A 2022 proof-of-concept study published in the International Journal of Peptide Research and Therapeutics demonstrated Stemokin's adjuvant properties in a murine influenza vaccination model. The study showed that Stemokin produced a balanced Th1/Th2 immune response superior to traditional aluminum hydroxide adjuvants, with enhanced IgG2a antibody production indicating improved cellular immunity.

A comprehensive 2023 review in the International Journal of Molecular Sciences documented the evolutionary development of Glu-Trp family peptides, confirming Stemokin's pronounced immuno- and hemostimulating effects in exogenous colony restoration models following bone marrow irradiation.

Earlier research (2007) published in International Immunopharmacology established the effects of EW dipeptide optical and chemical isomers on CFU-S populations, providing the foundational understanding of how Stemokin's specific amino acid configuration produces its hemostimulating properties.

Stacking

Stemokin may theoretically complement other peptides targeting different aspects of immune function or tissue repair. However, published research has primarily examined Stemokin as a standalone agent or in combination with vaccine antigens rather than with other peptide therapeutics.

The peptide has been studied in combination with:

• Influenza vaccine antigens (VAXIGRIP®) as an adjuvant
• Comparison protocols alongside G-CSF and GM-CSF for hematopoietic stimulation

Given Stemokin's action on early-stage hematopoiesis, theoretical stacking considerations might include peptides targeting later immune cell differentiation or tissue-specific regeneration, though such combinations lack published clinical evidence.

Reconstitution & Storage

Stemokin is typically supplied as a lyophilized powder requiring reconstitution before use.

Reconstitution protocol:

• Use sterile bacteriostatic water or sterile saline for reconstitution
• Direct the diluent stream against the vial wall rather than directly onto the powder
• Gently swirl until fully dissolved; do not shake vigorously
• Filter through 0.2 μm PVDF membrane for sterility assurance

Storage:

• Lyophilized powder: Store at -20°C or below, protected from light
• Reconstituted solution: Store at 2–8°C (refrigerated) and use within the manufacturer's specified timeframe
• Avoid repeated freeze-thaw cycles
• Serum samples in research were stored at -70°C until analysis

Side Effects

Published research indicates a favorable safety profile for Stemokin. In toxicological evaluations:

• No toxic effects were observed after single parenteral injection at doses up to 10,000 µg/kg in mice
• Three-month daily parenteral administration showed no significant adverse effects
• Unlike aluminum-based adjuvants, Stemokin solution does not cause local complications at injection sites

Potential side effects common to injectable peptides may include:

• Injection site reactions (redness, swelling, mild discomfort)
• Transient flu-like symptoms during immune activation
• Theoretical risk of immune overstimulation in susceptible individuals

Long-term human safety data remains limited, and individuals with autoimmune conditions, active malignancies, or compromised immune systems should exercise particular caution.

Legal Status / FDA

Stemokin is registered as a pharmaceutical drug in the Russian Federation under Russian Ministry of Health Registration Certificate № LCP-003014/09 dated April 16, 2009, where it is approved as an immune- and hemostimulatory agent.

In the United States, Stemokin is not FDA-approved for any indication. It falls under the category of research chemicals or unapproved peptides. The FDA has increasingly scrutinized compounded peptide therapies, and Stemokin would be classified as a non-approved substance requiring further clinical trials before potential approval.

In most Western jurisdictions, Stemokin may be legally obtained for research purposes but is not approved for human therapeutic use. Users should verify local regulations regarding peptide possession and use.

Sports / WADA

The World Anti-Doping Agency (WADA) maintains a Prohibited List that includes various peptide hormones and growth factors. While Stemokin is not specifically named on the WADA Prohibited List, its mechanism of action—stimulating hematopoietic stem cells and potentially affecting blood cell production—places it in a regulatory gray area.

WADA's prohibited categories include:

• S2: Peptide Hormones, Growth Factors, Related Substances, and Mimetics
• Non-approved substances that are not addressed by other sections of the list

Athletes subject to anti-doping regulations should consider that any substance affecting hematopoiesis or immune function may be scrutinized. The safest approach for competitive athletes is to verify the status of any peptide through GlobalDRO.com or consult with anti-doping authorities before use.

Conclusion

Stemokin represents a unique entry in the peptide therapeutics landscape, distinguished by its targeted action on early-stage hematopoietic stem cells rather than mature immune cells. The published research demonstrates meaningful hemostimulating and immunomodulatory effects, with a favorable safety profile in preclinical studies. Its ability to promote balanced Th1/Th2 immune responses and accelerate bone marrow recovery following damage positions it as a compound of interest for immune support and recovery applications.

However, prospective users should recognize that Stemokin remains unapproved outside Russia, with limited long-term human safety data. The existing evidence, while promising, derives primarily from animal models and early-stage human research. As with all unapproved peptides, informed decision-making requires weighing potential benefits against regulatory status, limited clinical evidence, and individual health considerations.

FAQ

What is Stemokin made of?
Stemokin is a synthetic tripeptide composed of three amino acids: L-isoleucine, L-glutamic acid, and L-tryptophan (Ile-Glu-Trp), supplied as a monosodium salt with 99.8% purity.

How does Stemokin differ from Thymogen?
While both peptides derive from thymus research, Stemokin (tripeptide Ile-Glu-Trp) acts on earlier stages of hematopoiesis at the CD34+ stem cell level, whereas Thymogen (dipeptide Glu-Trp) primarily affects more differentiated immune cells. Stemokin also demonstrates efficacy at higher radiation doses (4 Gy) where Thymogen shows reduced activity.

Is Stemokin approved for human use?
Stemokin is registered as a pharmaceutical drug in Russia but is not FDA-approved in the United States or approved by regulatory agencies in most Western countries.

What is the typical dosage range?
Research protocols have used doses ranging from 1 µg to 100 µg per administration, with higher doses (100 µg) producing the most pronounced immunomodulatory effects. Extrapolated human therapeutic doses are estimated at 10–100 µg/kg.

How long until results are noticeable?
Research indicates measurable immune response changes by day 14, with significant effects apparent by day 28 and peak responses achieved by day 42 following a two-dose protocol.

Can athletes use Stemokin?
Athletes subject to anti-doping regulations should exercise extreme caution. While not specifically named on WADA's Prohibited List, Stemokin's hematopoietic effects may fall under prohibited categories. Verification through official anti-doping resources is essential before use.

What are the main side effects?
Published research reports no significant adverse effects at therapeutic doses. Potential side effects may include injection site reactions and transient immune activation symptoms. Long-term human safety data remains limited.

How should Stemokin be stored?
Lyophilized powder should be stored at -20°C or below. Reconstituted solutions should be refrigerated at 2–8°C and used within the manufacturer's specified timeframe. Avoid repeated freeze-thaw cycles.

References:

1. Deigin V, Koroev D, Volpina O. Peptide ILE-GLU-TRP (Stemokin) Potential Adjuvant Stimulating a Balanced Immune Response. Int J Pept Res Ther. 2022;28(6):156. https://pmc.ncbi.nlm.nih.gov/articles/PMC9589648/
2. Deigin V, Linkova N, Volpina O. Advancement from Small Peptide Pharmaceuticals to Orally Active Piperazine-2,5-dion-Based Cyclopeptides. Int J Mol Sci. 2023;24(17):13534. https://www.mdpi.com/1422-0067/24/17/13534
3. Deigin VI, Semenets TN, Zamulaeva IA, et al. The effects of the EW dipeptide optical and chemical isomers on the CFU-S population in intact and irradiated mice. Int Immunopharmacol. 2007;7:375-382.
4. Semina OV, Semenets TN, Deigin VI, et al. Effect of the peptide of thymus original (synthetic peptide IEW) on hemopoietic cell progenitors in intact and irradiated animals. Immunol Lett. 1996;51:137-140.
5. Morozov VG, Khavinson VK. Natural and synthetic thymic peptides as therapeutics for immune dysfunction. Int J Immunopharmacol. 1997;19:501-505.
6. Gupta T, Gupta SK. Potential adjuvants for developing a SARS-CoV-2 vaccine based on experimental results from similar coronaviruses. Int Immunopharmacol. 2020;86:106717.
7. World Anti-Doping Agency. The Prohibited List. https://www.wada-ama.org/en/prohibited-list
8. U.S. Anti-Doping Agency. World Anti-Doping Agency (WADA) Prohibited List. https://www.usada.org/substances/prohibited-list/
9. Deigin V, Ksenofontova O, Khrushchev A, et al. Chemical Platform for the Preparation of Synthetic Orally Active Peptidomimetics with Hemoregulating Activity. ChemMedChem. 2016;11:1974-1977.
10. Semenets TN, Semina OV, Vinogradova YE, et al. Use of synthetic immunomodulating peptides to restore hematopoiesis in mice after cytostatic cytosine-arabinoside (Ara-C). Immunology. 2000;6:20-22.