Other compounds

Thymagen

Updated · 26 sources · Editorial policy

Thymagen, more often spelled Thymogen (or Timogen), is the trade name for a synthetic dipeptide, a chain of just two amino acids: glutamic acid and tryptophan (Glu-Trp, also written EW). Its international nonproprietary name is oglufanide. Russian researchers isolated it from Thymalin, a calf-thymus extract, and developed it in Russia as an “immunocorrector,” a drug meant to restore weakened immune function. Under the code IM862, the same dipeptide (as its disodium salt) was later tested in Western cancer trials as a blocker of blood-vessel growth.

The single most important fact: the largest and best-designed trial of this molecule, a 202-patient placebo-controlled phase III study in AIDS-related Kaposi sarcoma, found it no better than placebo. Thymogen is registered as a medicine in Russia, but it is not approved by the FDA or EMA. The Russian clinical literature is large but consists mostly of short reports whose abstracts give few numbers, and no human study has tested it for muscle, recovery or athletic performance.

This page summarizes what the published clinical trials, laboratory studies and regulators report. It is for education only and is not medical advice.

Property Detail
Class Synthetic dipeptide (L-glutamyl-L-tryptophan); thymic peptide immunomodulator
Other names Thymogen, Timogen, oglufanide (INN), Glu-Trp, EW; IM862 for oglufanide disodium (PubChem)
Formula and weight C₁₆H₁₉N₃O₅, 333.34 g/mol; disodium salt (IM862) 377.30 g/mol (PubChem)
Origin Isolated from Thymalin, a polypeptide extract of calf thymus, then made synthetically
Approval Registered in Russia (registration certificate dated June 10, 2009, per its developers); not FDA- or EMA-approved
Routes studied Intranasal and injected in Russian reports; intranasal drops in US and UK cancer trials
Doses in Western trials IM862 5 mg intranasally (Kaposi sarcoma); 20 mg intranasally three times daily (kidney cancer)
Best human evidence Phase III Kaposi sarcoma trial: response 23% vs 21% on placebo (not significant)
Half-life Not established; we found no published human pharmacokinetic study
WADA Not named on the 2026 list (see Regulatory status)

What it is

Oglufanide is the dipeptide L-α-glutamyl-L-tryptophan. PubChem lists “Thymogen,” “Timogen,” “oglufanide” and “Glu-Trp” as names for the same compound, and “IM862” and “oglufanide disodium” for its disodium salt (PubChem: oglufanide; PubChem: oglufanide disodium).

According to its developers at the St. Petersburg Institute of Bioregulation and Gerontology, Glu-Trp was isolated from Thymalin by high-performance liquid chromatography, and the drug Thymogen was then built on the synthesized dipeptide (Morozov and Khavinson, Int J Immunopharmacol 1997). A 2024 review by researchers from the same circle states that, of several tryptophan-containing dipeptides found in the Thymalin fraction, Glu-Trp showed the highest activity in their screening, and that Thymogen is registered with the Russian Ministry of Health (Deigin et al., Int J Mol Sci 2024).

Not the same as other “thymus” peptides

Several unrelated peptides carry thymus-related names. They differ in size, origin and evidence, and results for one do not apply to another.

Compound What it is Library page
Thymogen (oglufanide) Synthetic 2-amino-acid peptide, Glu-Trp This page
Thymalin Calf-thymus polypeptide extract from which Glu-Trp was isolated (Morozov and Khavinson 1997) Thymalin
Thymulin A 9-amino-acid, zinc-binding hormone made by the thymus (Dardenne et al., J Biol Chem 1977) Thymulin
Thymosin alpha-1 A 28-amino-acid thymic peptide; synthetic form thymalfasin (Goldstein et al., PNAS 1977) Thymosin Alpha-1
Thymosin beta-4 / TB-500 Tβ4 is a 43-amino-acid peptide (Low et al., PNAS 1981); TB-500 is a short synthetic fragment of it TB-500 (Thymosin Beta-4)

Thymogen also belongs to the family of short peptides the Khavinson group calls “bioregulators.” Others in the library include vilon, a synthetic dipeptide from the same group (Morozov and Khavinson 1997), pinealon, cartalax and epitalon. Each is a different molecule.

Mirror-image and look-alike versions

The biological effect of Glu-Trp depends on the exact form of its building blocks. Amino acids come in two mirror-image forms, L and D, and Thymogen uses the natural L forms. In mice, dipeptides built from D-glutamic acid suppressed blood-forming stem cells, while L-Glu-L-Trp did not affect them in healthy bone marrow and helped them recover after radiation (Deigin et al., Int Immunopharmacol 2007). A D-form version was developed in Russia as a separate drug, Thymodepressin, intended to suppress rather than stimulate immune responses (Deigin et al. 2024).

Golotimod (SCV-07) has the same formula as Thymogen but links a D-glutamic acid to tryptophan through a different bond, making it a distinct compound (PubChem: golotimod). Data on golotimod or Thymodepressin do not describe Thymogen.

How it works in the body

No mechanism has been confirmed in people. Proposed mechanisms come from cell and animal work:

  • Immune stimulation. The developers report that Glu-Trp activated T-cell differentiation, changed cyclic-nucleotide levels inside lymphocytes and activated neutrophil (a white blood cell) movement and engulfing of microbes (Morozov and Khavinson 1997).
  • Natural killer cells. In mice, Glu-Trp slowed tumor growth without killing tumor cells directly. The effect disappeared in mice lacking natural killer (NK) cell function or perforin, a protein NK cells use to kill targets, and was weaker in mice lacking interleukin-12 (Smith et al., Int J Cancer 2003).
  • Blood-vessel growth. IM862 was developed in the US as an angiogenesis inhibitor, a drug meant to block the growth of new blood vessels that feed tumors. An independent 2021 study found that Glu-Trp inhibited vessel sprouting in some laboratory and mouse assays, though another dipeptide (Trp-Leu) had stronger effects on VEGF receptor signaling (Khedr et al., Acta Physiol 2021).

Pharmacokinetics

We found no published study measuring the absorption, half-life or elimination of Glu-Trp in humans. Researchers developing oral versions described IM862 as highly water-soluble with low permeability across biological membranes, including the gut, “which makes it not orally available” (Bergeon and Toth, Bioorg Med Chem 2007). This is why the Western trials used nasal drops. Half-life figures quoted online are not based on published human measurements.

Regulatory status

  • Russia. Its developers state that Thymogen is registered with the Russian Ministry of Health, with a registration certificate dated June 10, 2009 (Deigin et al. 2024).
  • US and EU. We found no FDA or EMA approval. US trials of IM862 (oglufanide disodium) did not lead to approval, and one randomized phase II trial in colorectal cancer was terminated with the reason “Drug not available” (NCT00006037).
  • Sport. Glu-Trp is not named on the 2026 WADA Prohibited List. Class S0 bans any pharmacological substance not covered elsewhere on the list “with no current approval by any governmental regulatory health authority for human therapeutic use” (WADA 2026 Prohibited List). Because Thymogen is registered in Russia, it is unclear whether S0 applies; we found no WADA ruling specific to it.

What the research shows

Kaposi sarcoma (US trials of IM862)

Kaposi sarcoma is a tumor that arises from the cells lining blood vessels, which made it a logical first target for an angiogenesis inhibitor (Deplanque et al. 2004). It became the main test case for IM862.

Trial Design and n Dose Main result
Tulpule et al., J Clin Oncol 2000 Randomized comparison of two schedules, no placebo; 44 patients 5 mg intranasal drops, 5 days on/5 off or every other day Major responses in 36% (5 complete, 11 partial)
Noy et al., J Clin Oncol 2005 Randomized, double-blind, placebo-controlled phase III; 202 patients, 24 weeks 5 mg intranasally every other day Response 23% (95% CI 15–32%) vs 21% on placebo (95% CI 14–31%); not significant

The phase III trial also found that the median time to tumor progression was shorter on IM862: 16 weeks (95% CI 13–27) vs 35 weeks (95% CI 26–114) on placebo (p = 0.012). The authors concluded that IM862 “was not superior to placebo and may accelerate time to progression.” They pointed out that almost all patients were on highly active antiretroviral therapy (HIV drugs), which on its own produced sustained tumor responses and may have inflated the earlier, uncontrolled response rate. A 2022 systematic review of Kaposi sarcoma treatments found insufficient evidence to recommend any particular intervention (Liew et al., Int J Dermatol 2022).

Other cancers

Trial Design and n Result
Metastatic kidney cancer (Deplanque et al., Br J Cancer 2004) Single-arm phase II; 25 patients; 20 mg intranasally three times daily in 8-week cycles No objective responses; 8 stable disease, 17 progressed; median time to progression 1.9 months. Plasma VEGF fell at 4 and 8 weeks
Prostate cancer with rising PSA (Mao et al., Prostate 2007) Randomized, double-blind, placebo-controlled; 71 evaluable patients, added after hormone therapy Progression at 6 months in 41% on IM862 vs 49% on placebo (p = 0.39); not significant

Trials in recurrent ovarian cancer (phase I, 43 patients) and in ovarian and colorectal cancer combined with chemotherapy were registered, but we found no published results (NCT00003773; NCT00017303; NCT00006037).

Russian clinical reports

Russian clinical reports on Thymogen date back to at least the early 1990s, and the developers’ reviews summarize its use for disease prevention and treatment in people of different ages (Khavinson et al., Adv Gerontol 2013). Most of these papers are short, in Russian, and their abstracts give few or no numbers. Examples:

  • Respiratory infections. In a military training unit, intranasal and subcutaneous Thymogen was reported to reduce the rate, severity and duration of acute respiratory infections. The abstract gives no group sizes, control details or figures (Furgal et al., Voen Med Zh 1993).
  • Surgery in older adults. A double-blind, placebo-controlled trial gave intranasal Thymogen daily for 7 days before abdominal tumor surgery and reported fewer postoperative complications and shorter recovery. The abstract does not give the number of patients or the size of the effect (Smirnov et al., Adv Gerontol 2011).
  • Chronic atrophic gastritis. A multicenter, double-blind, placebo-controlled study of an oral Glu-Trp product (Regasthym Gastro) analyzed stomach biopsies from 116 patients. The number of glands per mm² of stomach lining rose 26.1% from baseline on the drug (p = 0.028), and differed from placebo (p = 0.026) (Baryshnikova et al., Arkh Patol 2023). A retrospective analysis of 80 patients from the same program reported less mucosal swelling and inflammation on endoscopy (Baryshnikova et al., Ter Arkh 2023).

These reports mostly measured immune cell counts or surrogate markers rather than hard outcomes, and we found no independent replication outside Russia. The only large, rigorous Western trials, in cancer, were negative.

Animal studies

Model Reported result
Female rats injected 5 μg Glu-Trp under the skin, 5 days a week for 12 months (Anisimov et al., Biogerontology 2000) Mean life span similar to controls; the longest-lived 10% lived longer (1,048 vs 949 days); total tumors 1.5-fold lower
Mice with influenza (Khavinson et al., Zh Mikrobiol Epidemiol Immunobiol 1993) Thymogen lowered deaths from influenza A, though less than the antiviral rimantadine, and had no effect on influenza B; no direct antiviral activity in chick embryos
Irradiated mice (Deigin et al. 2007) L-Glu-L-Trp injected after radiation promoted recovery of blood-forming progenitor cells

These results come from animals, mostly from the developers’ own groups, and have not been shown to apply to people.

Side effects and risks

What the trials reported

The Western cancer trials, which used IM862 nasal drops, reported low toxicity:

  • In the Kaposi sarcoma schedule trial, side effects were limited to mild, short-lived headache, fatigue, tingling and nausea, with no blood-count side effects attributed to the drug (Tulpule et al. 2000).
  • In the kidney cancer trial, no grade 2 or 3 toxicities related to the drug were recorded in 24 patients evaluable for safety (Deplanque et al. 2004).
  • In the prostate cancer trial, no significant toxicities emerged (Mao et al. 2007).

Possible harm in cancer

In the phase III Kaposi sarcoma trial, tumors progressed sooner on IM862 than on placebo (median 16 vs 35 weeks) (Noy et al. 2005). The authors could not rule out that the drug accelerated progression. Low side-effect rates therefore do not mean the drug is harmless in every condition.

Gaps in safety data

Long-term safety, effects in pregnancy and breastfeeding, and drug interactions have not been reported in the indexed literature. Thymogen is described as an immune stimulant, and its effects in people with autoimmune disease or on immunosuppressive drugs have not been studied in published trials.

Product quality

Outside Russia, products sold as “Thymagen” or “Thymogen” are not regulated medicines. Their identity, purity, dose and, for injectable forms, sterility are not independently verified.

Key takeaways

  • A two-amino-acid peptide. Thymogen (oglufanide, IM862) is Glu-Trp, isolated from the calf-thymus extract Thymalin and made synthetically. It is a different molecule from thymulin, thymosin alpha-1 and TB-500.
  • Registered in Russia, not in the US or EU. Its developers state it is registered with the Russian Ministry of Health; we found no FDA or EMA approval.
  • The best trial was negative. In a 202-patient placebo-controlled phase III trial in Kaposi sarcoma, response rates were 23% vs 21%, and tumors progressed sooner on the drug.
  • Other cancer trials also failed. It produced no objective responses in kidney cancer and did not delay PSA progression in prostate cancer.
  • Russian evidence is thin on detail. Many reports claim benefit in infections, surgery and gastritis, but most abstracts lack patient numbers and effect sizes, and none has been replicated independently.
  • No human pharmacokinetics. Its half-life in people has not been published, and it is poorly absorbed by mouth.

Sources

  1. National Center for Biotechnology Information. PubChem compound summary for CID 100094, Thymogen (oglufanide). PubChem.
  2. National Center for Biotechnology Information. PubChem compound summary for CID 158780, Glufanide disodium (oglufanide disodium, IM862). PubChem.
  3. National Center for Biotechnology Information. PubChem compound summary for CID 6992140, Golotimod. PubChem.
  4. Morozov VG, Khavinson VK. Natural and synthetic thymic peptides as therapeutics for immune dysfunction. Int J Immunopharmacol. 1997;19(9-10):501–505. PubMed.
  5. Deigin V, Linkova N, Vinogradova J, et al. The First Reciprocal Activities of Chiral Peptide Pharmaceuticals: Thymogen and Thymodepressin, as Examples. Int J Mol Sci. 2024;25(9):5042. PubMed.
  6. 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(3):375–382. PubMed.
  7. Dardenne M, Pleau JM, Man NK, Bach JF. Structural study of circulating thymic factor: a peptide isolated from pig serum. I. Isolation and purification. J Biol Chem. 1977;252(22):8040–8044. PubMed.
  8. Goldstein AL, Low TL, McAdoo M, et al. Thymosin alpha1: isolation and sequence analysis of an immunologically active thymic polypeptide. Proc Natl Acad Sci U S A. 1977;74(2):725–729. PubMed.
  9. Low TL, Hu SK, Goldstein AL. Complete amino acid sequence of bovine thymosin beta 4: a thymic hormone that induces terminal deoxynucleotidyl transferase activity in thymocyte populations. Proc Natl Acad Sci U S A. 1981;78(2):1162–1166. PubMed.
  10. Smith DL, Cai J, Zhu S, et al. Natural killer cell cytolytic activity is necessary for in vivo antitumor activity of the dipeptide L-glutamyl-L-tryptophan. Int J Cancer. 2003;106(4):528–533. PubMed.
  11. Khedr S, Klotzsche-von Ameln A, Khedr M, et al. Characterization of tryptophan-containing dipeptides for anti-angiogenic effects. Acta Physiol (Oxf). 2021;231(2):e13556. PubMed.
  12. Bergeon JA, Toth I. Enhancement of oral drug absorption-effect of lipid conjugation on the enzymatic stability and intestinal permeability of l-Glu-l-Trp-NH(2). Bioorg Med Chem. 2007;15(22):7048–7057. PubMed.
  13. 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. PubMed.
  14. 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. PubMed.
  15. Liew YCC, Tam YCS, Oh CC. Treatments for AIDS/HIV-related Kaposi sarcoma: A systematic review of the literature. Int J Dermatol. 2022;61(11):1311–1324. PubMed.
  16. 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. PubMed.
  17. Mao S, Daliani DD, Wang X, et al. Employing the treatment-free interval of intermittent androgen ablation to screen candidate prostate cancer therapies. Prostate. 2007;67(15):1677–1685. PubMed.
  18. ClinicalTrials.gov. IM-862 in Treating Patients With Recurrent Ovarian Cancer (NCT00003773); Combination Chemotherapy Plus IM-862 in Treating Patients With Resected Stage III Ovarian Cancer or Primary Peritoneal Cancer (NCT00017303); Chemotherapy Plus IM-862 in Treating Patients With Metastatic Colorectal Cancer (NCT00006037). NCT00003773; NCT00017303; NCT00006037.
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  20. Furgal SM, Degtiarev AA, Seryĭ SV, Khavinson VKh. The clinico-epidemiological efficacy of thymogen in acute respiratory viral infections in a military collective. In Russian. Voen Med Zh. 1993;(2):31–32, 80. PubMed.
  21. Smirnov VS, Petlenko SV, El’tsin SS. Application thymogen for preoperative preparation of elderly patients with tumor processes in abdominal cavity. In Russian. Adv Gerontol. 2011;24(2):278–284. PubMed.
  22. Baryshnikova NV, Uspensky YP, Fominykh YA, et al. Repair stimulator alpha-glutamyl-tryptophan in the complex therapy of chronic atrophic gastritis: results of histological examination. In Russian. Arkh Patol. 2023;85(3):54–63. PubMed.
  23. Baryshnikova NV, Uspenskiy YP, Fominykh YA, et al. Endoscopic and morphometric analysis of the reduction of acute inflammatory process in the gastric mucosa after therapy with Regasthym Gastro. In Russian. Ter Arkh. 2023;95(4):322–326. PubMed.
  24. Anisimov VN, Khavinson VK, Morozov VG. Immunomodulatory synthetic dipeptide L-Glu-L-Trp slows down aging and inhibits spontaneous carcinogenesis in rats. Biogerontology. 2000;1(1):55–59. PubMed.
  25. Khavinson VKh, Kozhemiakin AL, Volgarev AP, Platonov VG. The protective effect of peptides from the thymus and tracheal mucosa in an experimental respiratory influenzal infection. In Russian. Zh Mikrobiol Epidemiol Immunobiol. 1993;(1):68–73. PubMed.
  26. World Anti-Doping Agency. The 2026 Prohibited List. In effect January 1, 2026. WADA.