Thymagen Research

Thymagen research splits along language lines. The compound is the dipeptide alpha-glutamyl-tryptophan, and it is the active substance of medicines registered in Russia ^[18]. The same molecule carries the international non-proprietary name oglufanide and the development code IM-862 ^[17]. Under those names it went through a Western oncology program that ended without demonstrated clinical benefit in three cancers ^[1][2][3]. Both records are real. The second is rarely quoted.

What Thymagen is

Thymagen, also written Thymogen, is a synthetic dipeptide of glutamic acid and tryptophan. PubChem resolves the name Thymogen to record CID 100094, where the peptide bond runs from the alpha-carboxyl of glutamate and both residues are the L form ^[17]. The dipeptide was isolated from the calf-thymus extract Thymalin by reversed-phase chromatography, then made synthetically and named Thymogen by its originators ^[13]. Thymalin is a crude extract and a mixture rather than a defined compound ^[13]. Its clinical literature does not transfer to the isolated dipeptide.

The compound is supplied as research-grade material Thymagen. Research-grade material is not a medicine and is not for human consumption.

Four molecules share one shorthand

"Glu-Trp" is not a sufficient identifier for this compound. Four PubChem records in this family share the same molecular formula and the same mass ^[17]. They fall on two skeletons, distinguished by which glutamate carboxyl carries the peptide bond ^[17]. One of the four sits on the alpha skeleton, CID 100094, and that is the sold molecule ^[17]. The other three sit on the gamma skeleton, CID 6992140, CID 3038501 and CID 7275810 ^[17].

CID 6992140 is SCV-07, which ran its own Western trials in hepatitis C and oral mucositis, and those trials are not evidence for this compound ^[17]. The trial registry indexes one of those SCV-07 studies under the name glutamyl-tryptophan, which fits all four molecules ^[17].

CID 7275810 is Thymodepressin, marketed in Russia as an immunosuppressant ^[9][17]. A 2024 review describes Thymogen and Thymodepressin as an enantiomeric pair ^[9]. The PubChem records do not support that description. Thymodepressin sits on the gamma skeleton while the sold molecule sits on the alpha, so the two are constitutional isomers rather than mirror images ^[17]. No marketed product was identified for the actual mirror image of the sold molecule ^[17].

Two further confusions recur around this compound. Thymosin alpha-1 is a separate 28-residue peptide with a different molecular formula, and any approvals it holds cannot transfer to this dipeptide ^[17]. Cytovir-3 is a Russian combination product containing this dipeptide plus two other actives, so its effects cannot be assigned to the dipeptide alone ^[14].

Regulatory status

Alpha-glutamyl-tryptophan is the active substance of medicines registered in Russia and currently marketed there ^[18]. Russian drug references name the authorization holder as AO MBNPK Tsitomed and file the substance under ATC code L03AX, "other immunostimulants" ^[18]. The Russian state register gates its search behind a CAPTCHA and was not read directly, so the registration is corroborated by converging drug references rather than confirmed at source ^[18].

Three of the four registered Russian indications are adjunct therapy in respiratory infection, immune suppression after surgery or trauma, and immunodeficiency during radiotherapy, chemotherapy or antibiotic therapy ^[18]. The fourth is atrophic gastritis, registered for the oral form ^[18]. None of these registered uses concerns physique, recovery or general wellness. That authorization covers registered Russian medicines, not research-grade material sold for laboratory use.

There is no United States approval. The substance is absent from Drugs@FDA at product level, so no marketing application for it appears in the public record ^[17]. Two entries are routinely misread as approvals. The FDA substance registration system validated a unique ingredient identifier for the molecule, which assigns an identifier and does not approve a drug ^[17]. An FDA orphan drug designation for ovarian cancer is recorded for 2001, and it was never converted into an approval ^[17]. Designation is an incentive granted on disease rarity, not a finding of efficacy. No EMA marketing authorization and no EMA orphan designation were found ^[17].

Thymagen research in humans

The decisive human evidence on this molecule is Western, and it is independent of the Russian originators ^[1][2][3]. Both Western trials that reported a placebo comparison failed ^[1][3]. A randomized, double-blind, placebo-controlled Phase III trial in AIDS-related Kaposi's sarcoma enrolled 202 HIV-positive patients ^[1]. Response rates were 23 percent on drug and 21 percent on placebo, p = 0.46 ^[1]. Median time to progression was shorter on drug than on placebo, 16 weeks against 35 weeks, p = 0.012 ^[1]. The authors conclude the compound was not superior to placebo, may accelerate time to progression, and attribute much of the earlier apparent benefit to concurrent antiretroviral therapy ^[1].

The number still quoted for this compound comes from that earlier apparent benefit. A randomized Phase II with two schedules and no placebo arm reported major responses in 36 percent of 44 patients ^[4]. The Phase III overturned it ^[1]. An independent 2022 systematic review of AIDS-related Kaposi's sarcoma treatments in humans lists this compound among therapies of varied efficacy ^[15]. That review reports the efficacy evidence across the field as varied and insufficient, with a lack of standardization preventing meaningful comparison ^[15].

A prospective single-arm Phase II in metastatic renal cell carcinoma enrolled 25 patients and produced no objective responses ^[2]. Its authors recommend against further single-agent evaluation in that population at the dose and schedule tested ^[2]. Plasma VEGF nonetheless fell significantly during treatment, so the biomarker moved while the clinical outcome did not ^[2].

A randomized, double-blind, placebo-controlled Phase II in prostate cancer enrolled 71 evaluable patients ^[3]. PSA had progressed at six months in 41 percent on drug and 49 percent on placebo, p = 0.39 ^[3]. The authors report a failure to demonstrate superiority over placebo on time to PSA progression ^[3].

The strongest recent Russian human study is a multicenter, double-blind, randomized, placebo-controlled trial in Helicobacter pylori-associated chronic atrophic gastritis ^[10]. Biopsies from 116 patients were assessed by blinded histomorphometry and immunohistochemistry ^[10]. Glands per square millimeter of gastric mucosa rose 26.1 percent against baseline, p = 0.028, and against placebo, p = 0.026 ^[10]. A companion paper reports a retrospective endoscopic and morphometric analysis of 80 patients from the same program ^[11]. That companion is a secondary analysis rather than an independent replication. No ClinicalTrials.gov record for the trial was located ^[17]. The trial's endpoint is gastric mucosal repair rather than immune function ^[10].

Preclinical research

Independent Western preclinical work on this molecule includes three mechanistic studies ^[5][6][7]. In mice, the dipeptide inhibited tumor growth without direct cytotoxicity against human tumor cell lines ^[5]. Antitumor activity required natural killer cells and absolutely required perforin, was intact in interferon-gamma knockout mice, and was diminished in interleukin-12 knockouts ^[5]. That points to an immune-mediated mechanism rather than direct anti-tumor action. It is an animal finding, and the human trials above did not confirm it.

A German group screened tryptophan dipeptides for anti-angiogenic effects in cell, tissue and embryo assays, and this dipeptide was not the best performer ^[6]. A different dipeptide had the strongest effect on VEGFR-2 signaling and on the pathways downstream of it ^[6]. This dipeptide did inhibit sprouting in one in vitro assay where that comparator did not ^[6]. This dipeptide and that comparator both reduced vessel number in the chick membrane assay and in mouse aortic ring sprouting ^[6]. Those are tissue and embryo assays, and that screen ran no animal disease model ^[6]. In the same group's in vitro ACE-inhibition work in human endothelial cells, it ranked behind another tryptophan dipeptide and ahead of a third ^[7]. None of the peptides tested changed basal vessel tone in rat aorta, which is ex vivo animal tissue ^[7]. The in vivo arm of that study used a different peptide, so it yields no in vivo blood-pressure result for this molecule ^[7].

Stereochemistry changes the direction of effect within this peptide family. In mouse bone-marrow work, D-configured Glu-Trp dipeptides inhibited spleen colony formation and suppressed stem cell entry into S-phase ^[8]. L-configured Glu-Trp dipeptides had no effect on intact marrow, and stimulated regeneration after irradiation ^[8]. That is animal and in vitro evidence.

One frequently cited rat study is routinely misreported. Mean lifespan was the same in treated and control rats, and only the mean lifespan of the last-surviving 10 percent differed ^[12]. Total tumor incidence was 1.5 times lower and malignant tumor incidence 1.7 times lower in treated rats ^[12]. The tumor finding is real in that dataset. A mean-lifespan extension is not.

A 2025 rat study of hydrazine liver injury reported inhibited lipid peroxidation and stimulated hepatocyte regeneration at the lower exposures tested ^[16]. The higher exposures produced no further hepatoprotective effect, and a modified analogue outperformed the parent compound ^[16].

Independence and gaps

The Russian literature on this compound is concentrated on the people who developed it. The dipeptide was isolated and named by Morozov and Khavinson, who built the St Petersburg institute around peptide bioregulators, and both are co-authors on the most-cited rat longevity paper ^[12][13]. Authors from that same institute appear on the modern gastritis papers and on the 2023 cell study ^[10][11][14]. AO MBNPK Tsitomed holds every Russian registration for this active substance and also makes the product those gastritis papers tested ^[10][11][18]. That makes the modern gastritis program manufacturer-adjacent research ^[10][11][18]. Neither gastritis paper carries a conflict-of-interest statement ^[17]. The chirality work comes from an investigator at a peptide engineering company ^[8][9]. That 2024 review declares no conflicts of interest, and its subject is a drug pair the same author is associated with developing ^[9].

No non-Russian, non-originator replication of the clinical immune claims was identified in the indexed literature. The independent Western clinical record includes three human trials in three cancers that found no clinical benefit ^[1][2][3], and three independent Western preclinical studies are mechanistic ^[5][6][7]. The usual defense of this literature, that no one outside Russia gave the compound a fair test, is unavailable here.

Parts of the development record simply stop. A Phase II in colorectal cancer was terminated after 18 patients, with the registry reason recorded verbatim as "Drug not available" ^[17]. A Phase II in resected stage III ovarian cancer is still listed as unknown status and was never reported ^[17]. A Phase I in recurrent ovarian cancer completed with 43 patients in 2001 and has posted no results ^[17]. A hepatitis C program recorded in a drug development database produced no registered trial and no indexed clinical publication ^[17].

Conclusion

Thymagen resolves to a single PubChem record, although the shorthand "Glu-Trp" is shared by four molecules ^[17]. Medicines containing the substance are registered in Russia, and research-grade material is not one of them ^[18]. Its decisive human evidence is Western and independent of the originators, and three Western human trials in three cancers found no clinical benefit ^[1][2][3]. In the Kaposi's sarcoma Phase III, median time to progression in humans was shorter on drug than on placebo, p = 0.012 ^[1]. The one recent placebo-controlled positive human trial is Russian, and measures gastric mucosal repair ^[10]. Registration and evidence are separate questions on this compound, and they point in different directions.

Frequently Asked Questions

Is Thymagen approved anywhere? Alpha-glutamyl-tryptophan is the active substance of medicines registered in Russia and currently marketed there, filed under ATC code L03AX ^[18]. That registration is corroborated by converging Russian drug references rather than read from the state register, which is CAPTCHA-gated ^[18]. That authorization covers registered Russian medicines, not research-grade material sold for laboratory use. There is no United States approval and no marketing application at product level in Drugs@FDA, and no EMA marketing authorization or orphan designation was found ^[17].

Are Thymogen and Thymodepressin enantiomers of each other? The PubChem records do not support that description, although a 2024 review uses it ^[9][17]. Thymodepressin, CID 7275810, sits on the gamma skeleton, while the sold molecule, CID 100094, sits on the alpha skeleton ^[17]. The two are therefore constitutional isomers rather than mirror images ^[17]. No marketed product was identified for the actual mirror image of the sold molecule ^[17].

Has the 36 percent Kaposi's sarcoma response rate held up? It has not: that figure comes from a randomized Phase II with two schedules and no placebo arm, in 44 patients ^[4]. The subsequent randomized, double-blind, placebo-controlled Phase III in 202 patients found 23 percent on drug against 21 percent on placebo, p = 0.46 ^[1]. Median time to progression in that human trial was shorter on drug than on placebo, 16 weeks against 35 weeks, p = 0.012 ^[1]. The authors write that the compound may accelerate time to progression, and attribute much of the earlier apparent benefit to concurrent antiretroviral therapy ^[1].

References

1. 1

   Noy A, Scadden DT, Lee J, Dezube BJ, Aboulafia D, Tulpule A, Walmsley S, Gill P. 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. J Clin Oncol. 2005 Feb 10;23(5):990-8. PMID 15598977. DOI: 10.1200/JCO.2005.11.043 (the abstract misnames the compound as "L-glutamine L-tryptophan"; the agent is IM862 throughout)
2. 2

   Deplanque G, Madhusudan S, Jones PH, Wellmann S, Christodoulos K, Talbot DC, Ganesan TS, Blann A, Harris AL. Phase II trial of the antiangiogenic agent IM862 in metastatic renal cell carcinoma. Br J Cancer. 2004 Nov 1;91(9):1645-50. PMID 15354209. DOI: 10.1038/sj.bjc.6602126
3. 3

   Mao S, Dorff TB, Tsao-Wei DD, Groshen S, Quinn DI, Pinski J. Employing the treatment-free interval of intermittent androgen ablation to screen candidate prostate cancer therapies. Prostate. 2007 Nov 1;67(15):1677-85. PMID 17879948. DOI: 10.1002/pros.20649
4. 4

   Tulpule A, Scadden DT, Espina BM, Cabriales S, Howard W, Shea K, Gill PS. Results of a randomized study of IM862 nasal solution in the treatment of AIDS-related Kaposi's sarcoma. J Clin Oncol. 2000 Feb;18(4):716-23. PMID 10673512. DOI: 10.1200/JCO.2000.18.4.716
5. 5

   Smith DL, 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 Sep 10;106(4):528-533. PMID 12845648. DOI: 10.1002/ijc.11253 (University of Southern California, Keck School of Medicine)
6. 6

   Khedr S, et al. Characterization of tryptophan-containing dipeptides for anti-angiogenic effects. Acta Physiol (Oxf). 2021 Feb;231(2):e13556. PMID 32894635. DOI: 10.1111/apha.13556 (Institute of Physiology, Technische Universitat Dresden)
7. 7

   Khedr S, et al. Effects of tryptophan-containing peptides on angiotensin-converting enzyme activity and vessel tone ex vivo and in vivo. Eur J Nutr. 2018 Apr;57(3):907-915. PMID 28102435. DOI: 10.1007/s00394-016-1374-y
8. 8

   Deigin VI, et al. Reciprocal effect of optical isomerism of EW-dipeptides on immune response. Immunol Lett. 1999 Mar 15;67(1):41-6. PMID 10217204. DOI: 10.1016/s0165-2478(98)00149-7 (Peptide Engineering Centre PEPTOS, Moscow)
9. 9

   Deigin V, et al. The First Reciprocal Activities of Chiral Peptide Pharmaceuticals: Thymogen and Thymodepressin, as Examples. Int J Mol Sci. 2024 May 6;25(9):5042. PMID 38732260. DOI: 10.3390/ijms25095042 (PubMed COI statement: "The authors declare no conflicts of interest")
10. 10

    Baryshnikova NV, et al. [Repair stimulator alpha-glutamyl-tryptophan in the complex therapy of chronic atrophic gastritis: results of histological examination]. Arkh Patol. 2023;85(3):54-63. PMID 37272441. DOI: 10.17116/patol20238503154 (in Russian; no COI statement in the PubMed record; author affiliations include the Saint-Petersburg Institute of Bioregulation and Gerontology)
11. 11

    Baryshnikova NV, et al. [Endoscopic and morphometric analysis of the reduction of acute inflammatory process in the gastric mucosa after therapy with Regasthym Gastro]. Ter Arkh. 2023 May 31;95(4):322-326. PMID 38158980. DOI: 10.26442/00403660.2023.04.202147 (in Russian; no COI statement in the PubMed record; author affiliations include the Saint Petersburg Institute of Bioregulation and Gerontology)
12. 12

    Anisimov VN, Khavinson VKh, Morozov VG. Immunomodulatory synthetic dipeptide L-Glu-L-Trp slows down aging and inhibits spontaneous carcinogenesis in rats. Biogerontology. 2000;1(1):55-9. PMID 11707921. DOI: 10.1023/a:1010042008969
13. 13

    Morozov VG, Khavinson VKh. Natural and synthetic thymic peptides as therapeutics for immune dysfunction. Int J Immunopharmacol. 1997 Sep-Oct;19(9-10):501-5. PMID 9637345. DOI: 10.1016/s0192-0561(97)00058-1
14. 14

    Golovacheva EG, et al. The Effect of Drugs with alpha-Glutamyl-Tryptophan for Cytokine Secretion and Level of Surface Molecule ICAM-1 In Vitro. Cell Tissue Biol. 2023;17(2):146-152. PMID 37131521. DOI: 10.1134/S1990519X23020050 (PubMed COI statement: "The authors declare that they have no conflicts of interest. Experiments involving animals or human beings have not been performed."; author affiliations include the St. Petersburg Institute of Bioregulation and Gerontology)
15. 15

    Liew YCC, Kwan Z, Tan KL, Lai YK, Tey KE. Treatments for AIDS/HIV-related Kaposi sarcoma: A systematic review of the literature. Int J Dermatol. 2022 Nov;61(11):1311-1324. PMID 35775738. DOI: 10.1111/ijd.16318
16. 16

    Chulanova AA, et al. Hepatoprotective Effects of Thymogen Analogues in Hydrazine Hepatopathy in Rats. Bull Exp Biol Med. 2025 Apr;178(6):722-725. PMID 40442470. DOI: 10.1007/s10517-025-06405-y
17. 17

    Database records, retrieved live on 28 August 2026. PubChem PUG-REST: name/Thymogen returns CID 100094, InChIKey LLEUXCDZPQOJMY-AAEUAGOBSA-N, IUPAC name (4S)-4-amino-5-[[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino]-5-oxopentanoic acid, both stereocentres therefore in the L configuration; name/Thymodepressin returns CID 7275810, InChIKey CATMPQFFVNKDEY-DGCLKSJQSA-N; name/SCV-07 returns CID 6992140, InChIKey CATMPQFFVNKDEY-YPMHNXCESA-N; cid/3038501 returns InChIKey CATMPQFFVNKDEY-AAEUAGOBSA-N. All four share one molecular formula and a molecular weight of 333.34, and the first InChIKey block separates the alpha skeleton (CID 100094) from the gamma skeleton (the other three). The CID 100094 synonym list includes "Oglufanide [INN]", "Thymogen", "IM 862 dipeptide" and "EW dipeptide". Thymosin alpha-1 is CID 16130571, formula C129H215N33O55. ClinicalTrials.gov API v2: NCT00006037, Phase 2, University of Southern California, TERMINATED, enrollment 18 actual, whyStopped "Drug not available"; NCT00017303, Phase 2, sponsor Cytran, status UNKNOWN, last update posted 6 November 2013, hasResults false; NCT00003773, Phase 1, University of Southern California, COMPLETED, enrollment 43 actual, completion August 2001, hasResults false; NCT00002445, Phase 3, sponsor Cytran, COMPLETED. Term searches for "thymogen" and "Regastim" return no studies; a term search for "glutamyl-tryptophan" returns NCT00968357, an SCV-07 study sponsored by SciClone. SCV-07 carries its own registered studies in hepatitis C and oral mucositis, all sponsored by SciClone: NCT00968357, NCT00756951 and NCT01310205 are COMPLETED and NCT01247246 is UNKNOWN. No hepatitis C study for IM-862 or oglufanide is registered, and a PubMed search for "oglufanide" returns two records, PMIDs 37847482 and 16179960, neither a clinical result; the hepatitis C program is recorded only in the NCATS Inxight Drugs entry for oglufanide, which states it was run in Australia. openFDA drug/label: openfda.substance_name and openfda.generic_name queries for oglufanide and thymogen all return NOT_FOUND. openFDA drug/drugsfda: products.active_ingredients.name:oglufanide and products.brand_name:thymogen return NOT_FOUND, with positive control products.active_ingredients.name:IBUPROFEN returning 272. FDA UNII 4RHY598T5U is a substance registration record. The FDA orphan drug designation for ovarian cancer, September 2001, is taken from the NCATS Inxight Drugs record for oglufanide; the FDA orphan portal itself was not read. EMA searches returned no marketing authorization and no orphan designation. PubMed E-utilities efetch confirmed the author, journal, year and abstract text of every reference above, and the presence or absence of a COI statement on references 9, 10, 11 and 14.
18. 18

    Russian registration, corroborated on 28 August 2026 from GRLS-mirroring Russian drug references rather than from the state register. Alpha-glutamyl-tryptophan is the active substance of medicines held by AO MBNPK Tsitomed (Cytomed), St Petersburg, classified under ATC code L03AX ("other immunostimulants"). Three single-ingredient Thymogen presentations are listed as currently marketed: a cream, a nasal spray and a solution for intramuscular injection. A separate oral form, Regastim Gastro, is registered for atrophic gastritis. The registered indications across these forms are adjunct therapy in respiratory infection, immune suppression after surgery or trauma, immunodeficiency during radiotherapy, chemotherapy or antibiotic therapy, and atrophic gastritis. The nasal spray certificate LP-No.(000640)-(RG-RU), dated 24 March 2022, holder AO MBNPK Tsitomed, was independently confirmed; the certificate numbers for the other presentations were not. The Russian State Register of Medicines (grls.rosminzdrav.ru) gates its search behind a CAPTCHA and was not read.