Thymogen peptide: the Glu-Trp dipeptide, what the trials found and what is unknown

Thymogen is one of the shortest peptides sold as a research product: two amino acids, glutamic acid and tryptophan, joined by a single peptide bond. It came out of the same St Petersburg programme that produced thymalin, a mixture of peptides extracted from calf thymus. In 2000 Anisimov, Khavinson and Morozov described how the immunomodulatory molecule L-Glu-L-Trp was isolated from thymalin by reverse-phase liquid chromatography, synthesised, and turned into a pharmaceutical that received the brand name Thymogen ^[1]. That history makes thymogen a Khavinson bioregulator, or in supplier shorthand a thymogen bioregulator peptide, in the sense used by the St Petersburg group, but unlike most of the others in that family it went on to become a registered medicine.

The name is spelled several ways. Russian-language papers transliterate it as Timogen or Thymogen, some suppliers list it as Thymagen, and pharmacology papers refer to it by its structure, Glu-Trp, EW or L-glutamyl-L-tryptophan. In the United States the identical dipeptide was developed by Cytran under the code IM862, usually as the disodium salt, and published as an angiogenesis inhibitor ^[6]. A 2022 review from the Khavinson institute lists Thymogen (EW) as an immunoprotector and a medicinal product ^[11]. All of these are the same two-amino-acid molecule.

Thymogen sits in a small family of very short immune peptides. Its closest relatives on this site are thymalin, the parent extract, vilon, the Lys-Glu dipeptide from the same group, and crystagen, the Glu-Asp-Pro tripeptide the institute describes as an immunoprotector. The natural thymic hormone thymulin and the licensed drug thymosin alpha-1 are unrelated in structure but are often discussed alongside it.

Two very different mechanisms have been proposed by two very different research communities. The St Petersburg group describes thymogen as an immunomodulator: in their account it activates T-cell differentiation, T-cell recognition of peptide-MHC complexes, changes cyclic nucleotide levels inside cells, and activates neutrophil chemotaxis and phagocytosis ^[1]. In cultured human THP-1 monocytes, a 2022 Italian and Russian collaboration found that thymogen, along with epitalon, vilon, thymalin and chonluten, increased tyrosine phosphorylation of mitogen-activated kinases and reduced the release of TNF and IL-6 from cells stimulated with bacterial lipopolysaccharide ^[12]. A 2014 Russian study of ageing spleen tissue reported that thymogen activated B cells by reducing apoptosis and increasing proliferation of spleen cells ^[13].

The American work on IM862 focused instead on natural killer cells and blood vessels. Smith and colleagues at the University of Southern California showed in 2003 that the dipeptide inhibits tumour growth in mice without direct toxicity to tumour cells, and that the effect depended entirely on natural killer cell cytolytic activity and on perforin; it was lost in mice lacking NK cells and was partly dependent on IL-12 but not on interferon gamma ^[9]. IM862 was described in its clinical trials as a naturally occurring dipeptide with antiangiogenic properties, and one trial found that it lowered plasma VEGF levels after four and eight weeks of treatment ^[8].

A 2024 review by Deigin and colleagues adds a chemical twist. Thymogen (L-Glu-L-Trp) is an immunostimulant, while the mirror-image molecule made from D-amino acids, D-Glu(D-Trp), was developed in Russia as an immunosuppressant under the name Thymodepressin. The authors present this pair as the first example of enantiomeric peptide drugs with opposite effects on immune homeostasis ^[10]. A 2022 review from the Khavinson institute proposes that di- and tripeptides such as Glu-Trp enter cells through the PEPT and LAT transporter families, which would explain how a two-amino-acid molecule could act inside cells ^[11].

None of these accounts has been tested in a way that would let a reader choose between them. The immunological claims come from one group and its collaborators, and the NK-cell and antiangiogenic claims come from a company-sponsored programme that ended after a failed phase 3 trial.

Searches for thymogen benefits usually mean immune support, infection recovery, healing and anti-ageing. The animal literature is more substantial than for most Khavinson peptides, but it is still small and old. In the 2000 Biogerontology study, 44 female rats received 5 µg of L-Glu-L-Trp by subcutaneous injection five times a week for 12 months, compared with 32 saline controls. Mean life span was the same in both groups, but the life span of the longest-lived 10 per cent was 1048 days in treated rats against 949 days in controls, total tumour incidence was 1.5 times lower, malignant tumours 1.7 times lower, and leukaemias and lymphomas 3.4 times lower ^[1]. An earlier 1989 study gave thymogen at 10 µg per rat daily for 32 weeks to rats that had been fed an oesophageal carcinogen; tumour incidence fell by 12 per cent and the number of tumours per rat was 1.7 times lower ^[15].

Liver repair is a newer line of animal work. Researchers at Kursk State Medical University reported in 2023 that thymogen and two analogues with a D-alanine added to either end reduced lipid peroxidation and stimulated regeneration of liver cells in rats given carbon tetrachloride, with the analogues outperforming the parent dipeptide ^[14]. These are toxic-injury models in rats and say nothing about liver health in people.

In cell culture, the 2022 THP-1 study found that all five Khavinson peptides tested, including thymogen, reduced the LPS-stimulated release of TNF and IL-6 and reduced the adhesion of monocytes to activated endothelial cells, a pattern the authors interpreted as induction of TNF tolerance ^[12]. Whether a dipeptide taken by injection or nasal drops reaches immune cells at the concentrations used in that dish is unknown.

The Russian clinical literature makes broad claims, summarised in a 2013 review by Khavinson, Kuznik and Ryzhak that groups thymogen with thymalin, vilon, epithalamin, cortexin and other peptide preparations used for prevention and treatment across age groups ^[16]. That review is by the developers, in Russian, and does not report the underlying trial designs, so it cannot be treated as independent evidence of benefit.

Thymogen has been given to people in two settings: as an immunomodulator in Russian and Ukrainian hospitals, and as IM862 in North American and British cancer trials. The two literatures rarely cite each other.

Russian studies: in 1992 Tsvelev, Khavinson and colleagues reported using thymogen in the combined treatment of 46 women with acute endomyometritis, exacerbations of chronic salpingo-oophoritis or tubo-ovarian abscess, and described normalisation of lymphocyte counts and T-cell function with no complications ^[3]. A 1999 military medicine paper reported that thymogen stimulated T-cell immunity in patients with destructive pulmonary tuberculosis, given as two courses of ten 1 ml injections of a 1 per cent solution every two days ^[4]. A 2000 study of 48 patients with acute pancreatitis reported that adding 0.5 to 0.8 mg of thymogen per course corrected T-cell deficits ^[5]. The strongest design is a double-blind, randomised, placebo-controlled study published in 2011: elderly patients awaiting surgery for abdominal tumours received intranasal thymogen or saline once a day for seven days before the operation, and the authors reported restored cellular immunity and fewer postoperative complications ^[2]. None of these papers is available in English beyond the abstract, and sample sizes and outcome definitions are not reported in the abstracts.

IM862 in Kaposi’s sarcoma: a 2000 randomised study at the University of Southern California gave 44 patients with AIDS-related Kaposi’s sarcoma 5 mg of IM862 as nasal drops on one of two schedules. Major responses were seen in 36 per cent, with five complete and eleven partial remissions, and adverse effects were limited to mild, transient headache, fatigue, tingling and nausea ^[7]. That result led to a 24-week randomised, double-blind, placebo-controlled phase 3 trial of 202 HIV-positive patients run by the AIDS Malignancy Consortium and registered as NCT00002445 ^[17]. Published in 2005, it found no difference in response rate (23 per cent with IM862 against 21 per cent with placebo), and IM862 was associated with a shorter median time to progression, 16 weeks against 35 weeks. The authors concluded that antiretroviral therapy alone explained the earlier promising results and that IM862 might accelerate progression ^[6].

IM862 in other cancers: a British phase 2 trial in 25 patients with metastatic renal cell carcinoma gave 20 mg intranasally three times daily in eight-week cycles. There were no grade 2 or 3 toxicities, eight patients had stable disease, none had an objective response, and the authors said the drug should not be evaluated further as a single agent at that dose ^[8]. ClinicalTrials.gov also lists a completed phase 1 study in recurrent ovarian cancer, a phase 2 study with chemotherapy in resected ovarian and peritoneal cancer whose status is unknown, and a terminated study with chemotherapy in metastatic colorectal cancer ^[17].

Taken together, the human evidence for the thymogen dipeptide is: one Russian double-blind trial with limited reporting, several uncontrolled Russian and Ukrainian case series, one positive early cancer study and one large negative phase 3 trial. There are no published trials of thymogen for general immune support in healthy people, for anti-ageing, or for any of the uses suggested on supplier websites.

In the Russian surgical study, immune measures were assessed after a seven-day course of nasal drops ^[2]. In the Kaposi’s sarcoma study, responses appeared after a median of six weeks of nasal dosing ^[7], and in the phase 3 trial time to response was 8.5 weeks with IM862 against 14 weeks with placebo, a difference that did not translate into a higher response rate ^[6]. These timelines describe hospital treatment of specific conditions, not what a person buying thymogen online should expect.

The doses reported in the literature span several orders of magnitude depending on the route and the indication, and none of them is a recommendation. In Russian practice, thymogen was given by intramuscular injection of a 0.01 per cent solution or as a nasal solution; the tuberculosis paper describes 1 ml injections of a 1 per cent solution in courses of ten ^[4], the pancreatitis paper gives 0.5 to 0.8 mg per treatment course ^[5], and the surgical trial used once-daily nasal instillation for seven days ^[2]. In rats, life span studies used 5 µg per animal by subcutaneous injection five times a week ^[1] and 10 µg per rat daily ^[15], while the liver studies used 10 and 100 µg/kg with no extra benefit at the higher dose ^[14].

The US IM862 programme used far larger amounts: 5 mg intranasally every other day in Kaposi’s sarcoma ^{[6] [7]} and 20 mg three times a day in renal cancer ^[8]. Note that the Kaposi’s sarcoma dose was well tolerated but not effective in the phase 3 trial. Suppliers typically sell thymogen as 10 mg or 20 mg vials of freeze-dried powder; to convert a vial into a concentration, use the thymogen calculator or the general peptide calculator. Because the dipeptide is highly water-soluble and poorly absorbed across the gut, a 2008 Australian study set out to improve its oral absorption by attaching lipid and sugar groups, which is an indication that plain oral Glu-Trp is not expected to be well absorbed ^[18].

Thymogen the medicine exists as an injectable solution and a nasal solution; Russian sources also describe a topical cream. IM862 was given as nasal drops in every published trial ^{[6] [7] [8]}. Research suppliers sell the dipeptide as a lyophilised powder for reconstitution with bacteriostatic water and as capsules. There are no published human pharmacokinetic data for the research-grade product by any route, and the enzymatic instability and low membrane permeability of the free dipeptide are documented ^[18].

The published safety record is reassuring at the doses used in trials but far from complete. In the 44-patient Kaposi’s sarcoma study, adverse effects were limited to mild and transient headache, fatigue, tingling and nausea, with no haematological toxicity ^[7]. The renal cancer trial recorded no grade 2 or 3 toxicities related to the drug in 24 evaluable patients ^[8], and the phase 3 trial found the drug tolerable ^[6]. The Russian gynaecology paper described a desensitising effect and no complications ^[3].

The most important safety signal is the phase 3 finding that IM862 was associated with a shorter time to progression of Kaposi’s sarcoma than placebo, 16 weeks against 35 weeks ^[6]. Whatever the mechanism, it means that an immune-active dipeptide sold as harmless was linked to a worse outcome in a large controlled trial. People with an active cancer or an immune condition should treat claims that thymogen supports the immune system with that result in mind. There are no data on use in pregnancy, in children, or alongside immunosuppressant medicines, and long-term safety data in healthy people do not exist.

Thymogen is not on the WADA Prohibited List by name, and we have not seen it on the FDA’s lists of bulk substances nominated for compounding. Neither statement means it has been assessed as safe. For rules on possession and sale, see our legal status overview.

Thymogen is a registered medicine in Russia, where it is sold as an immunomodulator; the Khavinson institute’s own 2022 review describes it as a medicinal product ^[11], and its Russian development history is described by its inventors ^[1]. A 2009 review of immunomodulators from the former Soviet countries lists Thymogen among the interferon-inducing preparations that are widely used there but virtually unknown in the West ^[19].

In the United States the dipeptide was investigated as IM862 under an investigational new drug programme but was never approved, and the sponsor’s trials ended after 2005 ^{[6] [17]}. It is not an approved medicine in the UK, EU, Canada or Australia. Products sold as Thymogen or Thymagen by research suppliers are unlicensed and are labelled for laboratory use only. See the UK, US and Europe pages for the rules that apply to buying and holding unlicensed peptides.

Thymogen is supplied as a freeze-dried powder that is stable at room temperature for shipping and is generally stored refrigerated, dry and away from light. Reconstituted solutions are kept cold and used within a limited period. Tryptophan-containing peptides are sensitive to light and oxidation, which is a reason to keep vials in the dark. See how to store peptides for general practice.

Because thymogen is only two amino acids long, it is cheap to synthesise and hard to get wrong, but the small size also means a certificate of analysis cannot tell you much from mass spectrometry alone; the expected mass is about 333 g/mol, and a COA should show purity by HPLC as well. Learn how to read a peptide COA and what third-party testing actually covers.

Compare thymogen prices across suppliers, including listings in the UK and US, and see our list of third-party tested suppliers. If a seller quotes the Russian clinical literature as proof that its research-grade product works, remember that the registered medicine and a research vial are not the same product and have not been tested against each other. Our guide to spotting a fake peptide supplier covers the other warning signs.