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bioregulator · immune

Thymogen

Also known as: EW, Glu-Trp, L-glutamyl-L-tryptophan, oglufanide, IM 862, IM862, Timogen

Human RCT draft

A synthetic dipeptide (Glu-Trp) marketed in Russia as a thymic immune bioregulator and, under the names oglufanide and IM-862, developed in the United States as an antiangiogenic cancer drug. That double life makes it the most unusual entry in this codex: it is the one Khavinson-adjacent peptide that a Western consortium took into a double-blind placebo-controlled phase III trial. That trial, in 202 patients with AIDS-related Kaposi sarcoma, found no benefit over placebo and a shorter time to progression.

Sequence
EW

Glu-Trp · 2 residues · 333.34 Da (computed)

Contains no lysine.

single source C16H19N3O5 333.34 Da (published)

Sequence source: PubChem CID 100094, synonym 'Glu-Trp'; composition gate matched C16H19N3O5 / 333.34 Da. Corroborated by the NLM MeSH Supplementary Concept 'thymogen' (entry terms L-glutamyl-L-tryptophan, L-Glu-L-Trp, IM 862 dipeptide) and by PMID 15354209, which prints 'L-glu-L-trp'. The resolver fired one rung, so the status stays single_source.

Khavinson lineage

Bioregulator context

Target tissue: thymus (immune)

That the immunological activity of the thymic extract Thymalin is carried by short dipeptide fragments within it, and that a synthetic dipeptide of two residues therefore reproduces the extract's effect on age-related immune decline without the extract.

Proposed to act as a tissue-specific transcriptional regulator in thymic and immune cells, in the same nuclear-binding framework the developers apply to the rest of the family. The Western programme proposed something different and unrelated — inhibition of angiogenesis — and tested it in cancer rather than in ageing.

Claimed vs established

Mechanism

Claimed

Restores cellular immunity, corrects immunodeficiency, and — in the Western development programme — inhibits tumour angiogenesis.

Actually established

In the human monocytic THP-1 line, the dipeptide reduced LPS-stimulated TNF and IL-6 expression and reduced adhesion to activated endothelium. In people, the antiangiogenic mechanism was tested directly and failed: a phase III trial found no response-rate advantage over placebo, and a phase II trial in renal cell carcinoma produced no objective responses despite a measurable fall in plasma VEGF. A mechanism that lowers a biomarker without changing an outcome is not an established mechanism of benefit.

Honest appraisal

How good is the evidence

Human RCT 2 human RCTs · 4 human trials · 1 animal

This is the best-evidenced substance in the bioregulator half of this codex, and the evidence mostly points down. Two double-blind placebo-controlled trials exist. The larger and better-reported one — 202 patients, AIDS Malignancy Consortium, published in the Journal of Clinical Oncology — found the dipeptide no better than placebo for Kaposi sarcoma and associated with a shorter median time to progression, and concluded that the earlier 36% response rate was probably an artefact of concurrent antiretroviral therapy. The other, a Russian-language study of preoperative immune preparation in elderly surgical patients, reports benefit but states no group sizes. A UK phase II in renal cell carcinoma produced zero objective responses.

Where this evidence comes from

Unusually for this family, the strongest evidence is not developer-authored: the phase III trial, the phase II Kaposi trial and the renal-cell trial come from Memorial Sloan-Kettering, USC and Oxford respectively, with no Russian author and no link to the originating institute. Khavinson appears on only one study here, the cell-culture work. The two research traditions on this molecule barely overlap, and the one that ran the rigorous trials got a negative result.

What is said vs what was shown

Claims, one at a time

Each claim carries its own evidence tier. A compound is never simply "well studied" — some of its claims may be, others not at all.

ClaimVerdictEvidenceBasis
Has antitumour activity contradicted Human RCT A 24-week randomised, double-blinded, placebo-controlled phase III trial in 202 HIV-positive patients (104 drug, 98 placebo) found response rates of 23% versus 21% (p=0.46) and a shorter median time to progression on drug (16 vs 35 weeks, p=0.012). The authors concluded the drug was not superior to placebo and may accelerate progression, and that the earlier open-label 36% response rate was probably attributable to antiretroviral therapy. A phase II in metastatic renal cell carcinoma produced no objective responses in 25 patients. This is the rare case in this codex where a marketing claim was tested properly and did not survive.
Restores cellular immunity and reduces post-operative complications mixed Human RCT A double-blind, randomised, placebo-controlled study of intranasal Thymogen given before abdominal tumour surgery in elderly patients reports restored cellular-immunity parameters and a significant reduction in the number and range of post-operative complications. The design is the strongest described anywhere in this family. The reporting is not: the abstract states no group sizes, no effect estimates, no primary endpoint and no confidence intervals, gives no author affiliations in the indexed record, and the paper is in Russian in a journal that carries much of this literature. A well-designed trial reported this thinly cannot carry the weight its design would otherwise earn.
Reduces inflammatory signalling in monocytes and macrophages mixed In vitro In the THP-1 monocytic line, the dipeptide was among five Khavinson peptides that inhibited LPS-stimulated TNF and IL-6 expression and reduced adhesion to activated endothelial cells. All five peptides behaved similarly, which weakens rather than supports the tissue-specificity claim the family rests on, and the effects are in an immortalised leukaemia cell line at concentrations chosen for being known to work in culture.
Protects the liver and stimulates tissue repair mixed Animal In rats with carbon-tetrachloride hepatopathy, Thymogen suppressed lipid peroxidation and stimulated hepatocyte regeneration — but the paper's own finding is that two D-alanine-extended analogues did so more strongly than Thymogen itself. The work comes from a Kursk group with no apparent link to the originating institute, which makes it the most independent animal data here and also makes clear that its interest is in the analogues, not the parent compound.
Thymogen is the synthetic dipeptide counterpart of the thymic extract Thymalin mixed In vitro The pairing is repeated everywhere, including by the developers, and the 2022 cell-culture paper tests 'the Thymogen dipeptide' and 'the Thymalin peptide complex' side by side as members of one product family. But the developers' 2023 paper names KE (vilon) and EW (thymogen) together as Thymalin's two active dipeptides, so the extract has at least two claimed synthetic counterparts and this codex's thymalin entry points at the other one. A separate review attributes the chemistry to a different group again, framing Thymogen as the L-enantiomer partner of the immunosuppressant Thymodepressin. Nothing read here settles the authorship or the pairing.
Primary sources

The studies themselves

StudyDesignSubjectsQuality
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
Noy A, Scadden DT, Lee J, Dezube BJ, Aboulafia D, Tulpule A, Walmsley S, Gill P · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2005 PMID 15598977 		rct / human 202 — 202 HIV-positive patients with Kaposi sarcoma, 104 on IM862 and 98 on placebo, treated for 24 weeks; multicentre US and Canadian consortium Human RCT
risk of bias: low
Results of a randomized study of IM862 nasal solution in the treatment of AIDS-related Kaposi's sarcoma
Tulpule A, Scadden DT, Espina BM, Cabriales S, Howard W, Shea K, Gill PS · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2000 PMID 10673512 		open_label_trial / human 44 — 44 patients with AIDS-related Kaposi sarcoma, median age 38; 75% had prior systemic chemotherapy; nearly all on concurrent protease inhibitors. Randomised between two dosing schedules, with no untreated or placebo arm Human trial
risk of bias: high
Phase II trial of the antiangiogenic agent IM862 in metastatic renal cell carcinoma
Deplanque G, Madhusudan S, Jones PH, Wellmann S, Christodoulos K, Talbot DC, Ganesan TS, Blann A, Harris AL · British journal of cancer · 2004 PMID 15354209 		open_label_trial / human 25 — 25 patients with metastatic renal cell carcinoma, median age 62, WHO performance status 0-2; single-arm two-stage phase II at the Cancer Research UK unit in Oxford Human trial
risk of bias: moderate
[Application thymogen for preoperative preparation of elderly patients with tumor processes in abdominal cavity]
Smirnov VS, Petlenko SV, El'tsin SS · Advances in gerontology = Uspekhi gerontologii · 2011 PMID 21957588 ru		 rct / human — Elderly patients scheduled for surgery on solid tumours of the abdominal cavity and retroperitoneal space; placebo group received isotonic sodium chloride on the same schedule. Group sizes are not stated in the abstract Human RCT
risk of bias: high
Peptides Regulating Proliferative Activity and Inflammatory Pathways in the Monocyte/Macrophage THP-1 Cell Line
Avolio F, Martinotti S, Khavinson VK, Esposito JE, Giambuzzi G, Marino A, Mironova E, Pulcini R, Robuffo I, Bologna G, Simeone P, Lanuti P, Guarnieri S, Trofimova S, Procopio AD, Toniato E · International journal of molecular sciences · 2022 PMID 35408963 		in_vitro / cell_culture — Human THP-1 monocytic leukaemia cells, PMA-differentiated, exposed to five Khavinson peptides including the Thymogen dipeptide; adhesion tested on LPS-activated HUVEC monolayers In vitro
risk of bias: high
authored by the developer
Reparative and Antioxidant Effects of New Analogues of Immunomodulator Thymogen in Experimental Model of Liver Damage
Chulanova AA, Smakhtin MY, Bobyntsev II, Mishina ES, Artyushkova EB, Smakhtina AM · Bulletin of experimental biology and medicine · 2023 PMID 37861903 		animal_controlled / rat — Rats given intragastric carbon tetrachloride for 5 days to induce acute toxic hepatopathy, then treated with Thymogen or with D-Ala-extended analogues Animal
risk of bias: high
The First Reciprocal Activities of Chiral Peptide Pharmaceuticals: Thymogen and Thymodepressin, as Examples
Deigin V, Linkova N, Vinogradova J, Vinogradov D, Polyakova V, Medvedev D, Krasichkov A, Volpina O · International journal of molecular sciences · 2024 PMID 38732260 		narrative_review / mixed — Review of the L- and D-enantiomeric pair Thymogen (L-Glu-L-Trp) and Thymodepressin (D-Glu-D-Trp), covering chirality, proteolytic stability and selected clinical results In vitro
risk of bias: high
authored by the developer
What we do not know
  • No trial has tested this dipeptide for the ageing or immune-decline indication it is actually marketed for. The rigorous trials tested cancer, and they were negative.
  • The single positive randomised trial reports no group sizes, no effect estimates and no affiliations, so its result cannot be weighed even though its design is the best in this family.
  • Whether Thymogen or Vilon is Thymalin's synthetic counterpart is unsettled; the two entries in this codex disagree, and both mappings appear in developer-authored papers.
  • The Russian transcriptional-regulation mechanism and the American antiangiogenic mechanism have never been tested against each other, and the two literatures do not cite one another.
  • No human pharmacokinetic data was found for the intranasal route that both trial programmes used, so it is not established how much intact dipeptide reaches circulation.
  • The phase III time-to-progression signal has never been retested, in that population or any other.
  • No dose is recorded on any study on this page, because no full text has been read.
  • The compound's chemical authorship is disputed in the sources read here: one review attributes the enantiomeric pair to a Moscow bioorganic-chemistry group rather than to the St Petersburg gerontology institute.
Discussion, not evidence

What people actually report

Read this differently from everything above. Public posts from Reddit and X. Nothing here has been verified beyond confirming the post exists, and community reports are the weakest tier this site recognises. Doses discussed in these threads are deliberately not reproduced.
  • interest in mast-cell activation syndrome
  • comparison or confusion with thymosin alpha-1
  • questions about brands

What people keep asking

  • Is Thymogen relevant to mast-cell activation syndrome?
  • How does Thymogen differ from thymosin alpha-1?
  • Which brands do community members discuss?