Thymagen

Dosing from the Literature

Published for immunity: in the Russian product instructions for Thymogen, 100 mcg once a day by intramuscular injection, or one 25 mcg spray in each nostril twice a day, for 3–10 days. Not published: a randomized trial for immunity outside Russia.

The injection and spray doses below are those in the Russian product instructions for Thymogen, the registered drug. IM862 is the code under which US and UK cancer trials gave the same L-Glu-L-Trp dipeptide in the nose (Deplanque et al., 2004).

What It Is

Thymagen — more commonly called Thymogen in the Russian pharmaceutical registry — is a synthetic dipeptide (a chain of 2 amino acids) consisting of L-glutamic acid and L-tryptophan linked by an amide bond (Glu-Trp; EW, one-letter code). Along with Vilon (Lys-Glu; KE), Thymagen is one of the two simplest members of the Khavinson bioregulator system — a remarkable biological property given its minimal molecular size (only two residues, ~333 Da). It is soluble, stable, and bioavailable by multiple routes.

The historical origin of Thymagen is specific: the molecule was isolated from the natural calf-thymus peptide complex known as Thymalin by reversed-phase high-performance liquid chromatography (RP-HPLC) by the Morozov-Khavinson group at the Saint Petersburg Institute of Bioregulation and Gerontology. After identification, it was synthesized chemically and characterized for biological activity, and a pharmaceutical preparation — Thymogen — was designed on the basis of the synthetic dipeptide. Both Thymalin (the complex) and Thymogen (the isolated dipeptide) remain in Russian clinical use.

Nomenclature is slightly confusing in the international community: the Russian pharmaceutical is Thymogen, which is the same molecule sometimes called Thymagen in Western research-peptide marketing. The underlying compound is the same Glu-Trp dipeptide; the naming difference is commercial and linguistic. Thymagen is also occasionally confused with Thymalin (the full peptide complex) and with Thymulin (a distinct thymic nonapeptide bound to zinc). These three are not interchangeable.

Thymagen sits within the Khavinson framework as an "immunocorrector" intended to restore balanced T-cell function in states of secondary immunodeficiency — not as a pure immunostimulant. The theoretical framing is that an appropriately functioning immune system requires correct T-cell subset balance, appropriate cytokine signaling, and adequate thymic education of naive T cells; Thymagen is proposed to support these processes without blanket-activating an already-competent immune system. In Russian clinical practice it has been used across chronic bronchopulmonary conditions, post-surgical immune support, radiation- or chemotherapy-induced immunosuppression, and as a general adjunct in geriatric and pediatric immune practice.

Who Khavinson was, and what his record supports →

Mechanism of Action

Thymagen's mechanism of action combines two proposed components: the broader Khavinson peptide-DNA framework (shared with all short Khavinson peptides) and specific immunomodulatory (adjusting the immune system up or down) effects documented in the Morozov-Khavinson Western-indexed literature.

• T-cell differentiation (Morozov & Khavinson, Int J Immunopharmacol 1997; PMID 9637345) — The group reported that Thymagen (EW dipeptide) and the natural Thymalin complex both activated T-cell differentiation (Morozov & Khavinson, 1997; Anisimov et al., 2001). Morozov and Khavinson (1997) reported parallel activity in T-cell recognition of peptide-MHC complexes and in intracellular cyclic-nucleotide composition.
• Cytokine secretion (IL-2, IFN) — Per the same foundational publication, both natural and synthetic thymic peptides changed cytokine secretion from blood lymphocytes, notably interleukin-2 and interferon (Morozov & Khavinson, 1997). The authors read their results as thymic peptides acting as cytokine antagonists in inflammation.
• Neutrophil chemotaxis (cell migration toward a signal) and phagocytosis — The group reported that its synthetic dipeptides, Thymagen among them, activated neutrophil chemotaxis and phagocytosis (Morozov & Khavinson, 1997; Anisimov et al., 2001) — an effect outside the T-cell lineage.
• THP-1 monocyte / macrophage regulation (Khavinson group, 2022; PMC8999041) — In the THP-1 human monocytic cell line capable of differentiating into macrophages, Thymogen (EW) and related Khavinson peptides regulated proliferation and inflammation-related gene expression. Provides a modern cellular framework for the Khavinson theory.
• Bidirectional immunomodulation — The Khavinson group proposes that delivering its peptides can normalize disturbed body functions (Khavinson, 2002; PMID 12374906). Thymogen's Russian instructions class it as an immunostimulant with a "regulating influence" on cellular and humoral immunity (Russian product instructions).
• CD4 / CD8 balance — Thymogen's Russian instructions say it raises the expression of differentiation receptors on lymphocytes and normalizes the counts of helper (CD4) and cytotoxic (CD8) T cells, and their ratio, in people with immune deficiencies (Russian product instructions). A 1996 Russian report in type 1 diabetes attributed its effect on secondary immune deficiency to activated T-cell differentiation (Zhuk & Galenok, 1996).
• Proposed gene regulation (Khavinson framework) — The Khavinson group reports that its short peptides change gene expression (Khavinson, 2002; PMID 12374906), and its co-authors cite evidence that such peptides can pass directly into the cell compartment that regulates gene expression (Avolio et al., 2022). The group names Glu-Trp among the components of Thymalin that regulate gene expression, differentiation, proliferation and apoptosis of immune cells (Khavinson et al., 2021; PMID 33575961). This model is specific to the Khavinson group's framework and has not been independently validated in mainstream immunology.
• Anti-neoplastic signal (Bespalov et al., 1989; PMID 2759010) — Early Russian-language work reported that Thymogen, 10 mcg per rat daily for 32 weeks after the carcinogen N-nitrososarcosine ethyl ester, cut the incidence of esophageal and forestomach tumors by 12% and their number per rat 1.7-fold in male rats. In people with cancer, trials of the same dipeptide found no tumor responses in kidney cancer (Deplanque et al., 2004) and no benefit over placebo in Kaposi's sarcoma (Noy et al., 2005).
• Ischemia-reperfusion modulation — A 1997 Russian publication (Eksp Klin Farmakol; PMID 9324392) reported Thymogen effects on ischemia-reperfusion physiology in the heart, suggesting bioactivity beyond the immune system.
• Absorption and breakdown — Thymogen's Russian instructions say it reaches the bloodstream quickly after injection or nasal spraying and is split by peptidases into L-glutamic acid and L-tryptophan (Russian product instructions). No human study of its absorption by mouth was found.

What the Research Shows

PubMed lists 106 records on Thymogen (searched October 4, 2026, under Thymogen, Timogen and PubMed's own Thymogen heading, which also gathers the US IM862 trials); 80 are in Russian, and Khavinson or Morozov is an author on 18 of them. Key studies:

• Morozov VG, Khavinson VK (Int J Immunopharmacol 1997; PMID 9637345) — "Natural and synthetic thymic peptides as therapeutics for immune dysfunction." Foundational Western-indexed characterization of Thymalin and Thymogen. Demonstrated parallel bioactivity of natural and synthetic thymic peptides in T-cell differentiation, peptide-MHC recognition, cytokine secretion, and phagocyte function.
• L-Glu-L-Trp dipeptide anti-aging and anti-carcinogenesis (Anisimov-Khavinson group; PMID 11707921) — "Immunomodulatory synthetic dipeptide L-Glu-L-Trp slows down aging and inhibits spontaneous carcinogenesis in rats." In 44 female rats given 5 mcg under the skin 5 days a week for 12 months, against 32 given saline, mean lifespan was similar, the longest-lived 10% lived longer (1,048 vs 949 days), and spontaneous tumors were 1.5 times less frequent. Methodology and group-sizes are typical of the Khavinson program.
• Bespalov et al. (Eksp Onkol 1989; PMID 2759010) — Inhibiting effect of Thymogen on development of N-nitrososarcosine-induced esophageal and forestomach tumors in rats. Russian-language chemoprevention paper.
• Zhuk & Galenok (Ter Arkh 1996; PMID 9026934) — "Thymogen in the treatment of type-1 diabetes mellitus." Russian clinical paper describing adjunctive Thymogen use in autoimmune diabetes — representative of the Russian immune-disease clinical tradition.
• Khmel'nitskii et al. Russian thymic peptide histology / pathology series — Multiple Russian-language publications characterizing Thymalin-fraction biology and clinical use.
• Ischemia-reperfusion paper (Eksp Klin Farmakol 1997;60(3):27-9; PMID 9324392) — "The effect of thymogen on the heart in ischemia and reperfusion." Rodent cardiac ischemia / reperfusion model showing protective effects.
• THP-1 monocyte/macrophage regulation (Khavinson group 2022; PMC8999041) — "Peptides Regulating Proliferative Activity and Inflammatory Pathways in the Monocyte/Macrophage THP-1 Cell Line." Modern mechanistic study in human cell line evaluating five Khavinson peptides (Epitalon, Vilon, Thymogen, Thymalin, Chonluten) as regulators of inflammation and proliferation.
• Khavinson VK, Bondarev IE, Butyugov AA (Bull Exp Biol Med 2003;135(6):590-592; PMID 12937682) — Epithalon (sister Khavinson peptide) induces telomerase (the enzyme that rebuilds chromosome caps) activity — establishes the methodological style of Khavinson group peptide-effect papers.
• Anisimov & Khavinson (Biogerontology 2010; PMID 19830585) — "Peptide bioregulation of aging: results and prospects." Review paper covering the broader Khavinson program including Thymogen.
• Khavinson VK et al. (Bull Exp Biol Med 2020; PMID 33237528) — Thymalin-derived peptides and hematopoietic stem cell differentiation: modern extension of the Thymalin / Thymogen framework.
• Khavinson VK et al. (2021; PMID 33575961) — "Results and Prospects of Using Activator of Hematopoietic Stem Cell Differentiation in Complex Therapy for Patients with COVID-19." An open-label randomized trial of Thymalin, the parent extract, not Thymagen, in hospitalized COVID-19 patients; it names Glu-Trp as one of Thymalin's active components.
• Russian registration — Thymogen is registered in Russia as a solution for intramuscular injection (no subcutaneous route), a nasal spray and a cream (Russian product instructions), and has been in clinical use there since at least the mid-1990s (Zhuk & Galenok, 1996).

Human Data

Summary of Thymagen's human evidence base:

• Russian clinical tradition — Multi-decade use in Russian immunology, infectious disease, and geriatric practice. Registered as Thymogen (pharmaceutical) and widely dispensed for secondary immunodeficiency, chronic bronchopulmonary disease, post-surgical immune support, and chemotherapy / radiotherapy adjunct.
• Type-1 diabetes adjunct (Zhuk & Galenok, 1996; PMID 9026934) — Small Russian clinical cohort reporting adjunct Thymogen use in type-1 diabetes with immunological monitoring. Cohort size and methodology typical of Russian clinical tradition.
• Recurrent respiratory infections — Russian practice literature in pediatric and adult populations with recurrent upper respiratory infections, reporting reduced infection frequency and improved T-cell indices after Thymogen courses.
• COVID-19 trial of the parent extract (Khavinson 2021; PMID 33575961) — An open-label randomized trial of Thymalin, not Thymagen: 10 mg intramuscularly once a day for 5 days added to standard care in 42 hospitalized adults with COVID-19, against 50 given standard care alone. The paper names Glu-Trp only as one of Thymalin's active components.
• US and UK trials of the same dipeptide (IM862) — Under the code IM862, L-Glu-L-Trp was given in the nose in US and UK cancer trials (Deplanque et al., 2004). In a randomized, placebo-controlled phase III trial in 202 people with AIDS-related Kaposi's sarcoma (5 mg every other day for 24 weeks), it did no better than placebo (Noy et al., 2005). No randomized trial of it for immunity outside Russia was found.
• No pharmacokinetic data in Western literature — Formal PK studies of intact EW dipeptide after oral, intranasal, or SubQ administration in humans are not published in PubMed-indexed English-language journals.
• Long safety record — Decades of Russian use across adults and children without major safety signals. Consistent with the broader Khavinson peptide-class practical safety track record.

Reconstitution & Storage

In Russia, Thymogen comes as a solution for intramuscular injection (100 mcg in a 1 mL ampoule), a nasal spray (25 mcg per spray) and a cream (Russian product instructions). Research-chemical sellers list the dipeptide as freeze-dried powder in vials.

• Storage (mixed) — One seller lists −20°C in single-use portions after mixing, used promptly and not frozen and thawed repeatedly.
• Nasal spray — The instructions describe priming the pump with a few presses before first use, then one press per dose with the nozzle held upright in the nostril (Russian product instructions).
• Appearance — The instructions describe the injection as a clear, colorless, odorless solution and the spray as a clear, colorless liquid that may smell of its preservative, benzalkonium chloride (Russian product instructions).

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Side Effects & Risks

Thymogen has been in Russian clinical use since at least the mid-1990s (Zhuk & Galenok, 1996). What its instructions and the trials of the same dipeptide report:

• Reported side effects, injection — The instructions for the intramuscular solution list allergic reactions as its only adverse reaction and hypersensitivity as its only contraindication (Russian product instructions).
• Reported side effects, nasal spray — The spray's instructions list allergic rhinitis: a swollen, stuffy, runny or itchy nose and repeated sneezing (Russian product instructions).
• Side effects in US and UK trials (IM862) — In 44 adults with AIDS-related Kaposi's sarcoma given 5 mg nasal drops, side effects were limited to mild, short-lived headache, fatigue, tingling and nausea (Tulpule et al., 2000). In 24 adults with kidney cancer given 20 mg three times a day, those judged probably drug-related were mild headache in four and two bouts of sinusitis (Deplanque et al., 2004).
• Cancer — In the placebo-controlled trial in 202 people with AIDS-related Kaposi's sarcoma, tumors progressed sooner on IM862 than on placebo (median 16 vs 35 weeks), and the authors wrote that it "may accelerate time to progression" (Noy et al., 2005). The Russian instructions list use after radiotherapy and chemotherapy (Russian product instructions).
• Autoimmune disease (theoretical) — The group reports that Thymogen activates T-cell differentiation (Morozov & Khavinson, 1997), so in theory it could affect autoimmune disease. The Russian instructions list no such contraindication (Russian product instructions), and a 1996 Russian report gave it to people with type 1 diabetes, an autoimmune disease (Zhuk & Galenok, 1996).
• Pregnancy and lactation — Because clinical data are insufficient, the Russian instructions allow use in pregnancy or breastfeeding only when the expected benefit to the mother outweighs the potential risk to the fetus or baby (Russian product instructions).
• Children — The Russian instructions cover the injection from 6 months of age and the spray from 1 year; safety and efficacy below those ages are not established (Russian product instructions).
• Drug interactions — The spray's instructions say it raises the effect of chemotherapy drugs (cytostatic and antibacterial) and radiotherapy and is not recommended with high-dose corticosteroids, whose immune-suppressing effect cancels its immunostimulating action; the injection's instructions list no interactions (Russian product instructions).
• Purity risk — It is sold outside Russia as a research chemical; a seller listing calls it "not a drug" and not evaluated by the FDA.
• Add-on use — The Russian instructions list Thymogen for combined ("complex") therapy of infections, alongside standard treatment (Russian product instructions).

Bloodwork & Monitoring

No trial, label or guideline found sets monitoring for Thymagen; the Russian product instructions list none (Russian product instructions). The 1996 Russian report in type 1 diabetes assessed laboratory signs of secondary immune deficiency (Zhuk & Galenok, 1996), and the UK kidney-cancer trial of IM862 measured blood VEGF, which fell after 4 and 8 weeks (Deplanque et al., 2004).

Commonly Stacked With

None of the studies cited on this page, nor the Russian product instructions, pairs Thymagen with another peptide.

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Legal Status

Related Compounds

Peptides people often cross-check against Thymagen:

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References

1. Morozov VG, Khavinson VKh. Natural and synthetic thymic peptides as therapeutics for immune dysfunction. Int J Immunopharmacol. 1997;19(9-10):501-505. doi:10.1016/S0192-0561(97)00058-1. (Foundational Western-indexed characterization of Thymalin and Thymogen.)
2. Anisimov VN, Khavinson VKh, Morozov VG. Immunomodulatory synthetic dipeptide L-Glu-L-Trp slows down aging and inhibits spontaneous carcinogenesis in rats. Biogerontology. 2001;2(1):47-55. PMID: 11707921. (Chronic rodent dosing — longevity and anti-carcinogenesis signal.)
3. Bespalov VG, Troian DN, Petrov AS, Morozov VG, Khavinson VKh. Ingibiruiushchii effekt timogena na razvitie opukholei pishchevoda i predzheludka, indutsirovannykh etilovym efirom N-nitrozosarkozina u krys [Inhibiting effect of thymogen on the development of tumors of the esophagus and forestomach induced by N-nitrososarcosine ethyl ester in rats]. Eksp Onkol. 1989;11(4):23-26. Russian. PMID: 2759010.
4. Zhuk EA, Galenok VA. Timogen v lechenii sakharnogo diabeta I tipa [Thymogen in the treatment of type-1 diabetes mellitus]. Ter Arkh. 1996;68(10):12-14. Russian. PMID: 9026934.
5. Filippova OV, Reznikov KM, Alabovskiĭ VV, Khamburov VV, Vinokurov AA. The effect of thymogen on the heart in ischemia and reperfusion]. Eksp Klin Farmakol. 1997;60(3):27-29. Russian. PMID: 9324392.
6. Avolio F, Martinotti S, Khavinson VK, et al. Peptides Regulating Proliferative Activity and Inflammatory Pathways in the Monocyte/Macrophage THP-1 Cell Line. Int J Mol Sci. 2022. PMC8999041. (Modern mechanistic study including Thymogen / Thymagen.)
7. Khavinson VK, Bondarev IE, Butyugov AA. Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells. Bull Exp Biol Med. 2003;135(6):590-592. PMID: 12937682. (Methodological style of Khavinson mechanistic papers.)
8. Khavinson VK. Peptides and Ageing. Neuroendocrinol Lett. 2002;23 Suppl 3:11-144. PMID: 12374906. (Foundational review of the Khavinson peptide bioregulator program.)
9. Khavinson VK, Malinin VV. Gerontological Aspects of Genome Peptide Regulation. Basel: Karger; 2005. DOI: 10.1159/isbn.978-3-318-01193-7.
10. Anisimov VN, Khavinson VKh. Peptide bioregulation of aging: results and prospects. Biogerontology. 2010;11(2):139-149. PMID: 19830585.
11. Khavinson VK, Kuznik BI, Trofimova SV, Volchkov VA, et al. Results and Prospects of Using Activator of Hematopoietic Stem Cell Differentiation in Complex Therapy for Patients with COVID-19. Stem Cell Rev Rep. 2021;17(1):285-290. PMID: 33575961.
12. Khavinson VK, Linkova NS, Trofimov AV, Polyakova VO, Sevostyanova NN, Kvetnoy IM. Morphofunctional fundamentals for peptide regulation of aging. Biology Bulletin Reviews. 2011;1(4):390-394. DOI: 10.1134/s2079086411040025. (Supporting mechanistic framework.)
13. Khavinson VK, Popovich IG, Linkova NS, Mironova ES, Ilina AR. Peptide regulation of cell differentiation, gene expression, and protein synthesis. Bull Exp Biol Med. 2021;170(5):707-711.
14. FDA. Bulk Drug Substances Nominated for Use in Compounding under Section 503A of the Federal Food, Drug, and Cosmetic Act. FDA.gov. Updated 2025–2026 (Thymagen / EW dipeptide / Thymogen not listed).
15. Cytomed. Тимоген (Thymogen; alpha-glutamyl-tryptophan): Russian product instructions, as summaries of product characteristics and patient leaflets for the solution for intramuscular injection, 100 mcg/mL (registration ЛП-№(001808)-(РГ-RU)), the nasal spray, 25 mcg/dose (ЛП-№(000640)-(РГ-RU), first registered in this form March 24, 2022), and the cream, 0.05% (ЛП-№(001824)-(РГ-RU)). cytomed.ru/product/thymogen/ (cytomed.ru/wp-content/uploads/2023/11/timogen-rastvor_ohlp.pdf; cytomed.ru/wp-content/uploads/timogen-sprej-ohlp.pdf) and timogen.ru/instruction/; registration numbers per vidal.ru. Read October 4, 2026. (In Russian. Doses for adults and children, indications, contraindications, side effects, interactions, pregnancy, storage and shelf life.)
16. Noy A, Scadden DT, Lee J, et al. Angiogenesis inhibitor IM862 is ineffective against AIDS-Kaposi's sarcoma in a phase III trial, but demonstrates sustained, potent effect of highly active antiretroviral therapy: from the AIDS Malignancy Consortium and IM862 Study Team. J Clin Oncol. 2005;23(5):990-998. PMID: 15598977. (IM862 is L-glutamyl-L-tryptophan; the abstract's "L-glutamine" is a slip.)
17. Tulpule A, Scadden DT, Espina BM, et al. Results of a randomized study of IM862 nasal solution in the treatment of AIDS-related Kaposi's sarcoma. J Clin Oncol. 2000;18(4):716-723. PMID: 10673512.
18. Deplanque G, Madhusudan S, Jones PH, et al. Phase II trial of the antiangiogenic agent IM862 in metastatic renal cell carcinoma. Br J Cancer. 2004;91(9):1645-1650. PMID: 15354209. (Calls IM862 "a naturally occurring dipeptide (L-glu-L-trp)".)
19. World Anti-Doping Agency. Prohibited List 2026 (in effect January 1, 2026). S0, Non-approved substances. wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf. Read October 3, 2026.

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