Preloaded Autoinjector | Thymogen | 3ml Pen | 10mg

The Thymogen pen is a preloaded 3ml research autoinjector holding L-alpha-glutamyl-L-tryptophan in solution at 6/3 mg/ml, giving 6mg of dipeptide in the device. One of the two residues is tryptophan, the most photo-labile amino acid found in peptides, which makes light protection here a chemical requirement rather than packaging habit.

Specification Table

What Changes When Glu-Trp Ships in Solution?

Two chemical routes open as soon as this dipeptide is dissolved: photo-oxidation of the tryptophan indole, and cyclisation of the N-terminal glutamate to pyroglutamate. A lyophilized cake keeps both effectively frozen; a sealed cartridge of water does not.

Tryptophan is the residue that sets this compound apart from the rest of the bioregulator family. Its indole ring absorbs at 280 nm, and absorbed energy drives oxidation through singlet-oxygen and radical routes to N-formylkynurenine, kynurenine and hydroxytryptophans. Pattison, Rahmanto and Davies reviewed that chemistry in 2012 and placed Trp at the top of the photo-lability ranking for peptide residues. Visible light is sufficient when a trace photosensitiser is present, and riboflavin or a dye contaminant at parts-per-million levels will do it. A device left under bench lighting is therefore being illuminated at wavelengths its own contents absorb.

The second route is quieter. Glutamic acid at a free N-terminus slowly closes on itself to give pyroglutamyl-tryptophan, losing 18 Da of water in the process. Chelius and colleagues characterised that reaction in 2006 and showed phosphate and citrate accelerate it. The result is an N-blocked molecule that is no longer L-alpha-glutamyl-L-tryptophan, and nothing about the appearance of the solution changes when it happens. Peptides in this catalogue that begin with lysine or alanine have no such route.

A third possibility is diketopiperazine closure, in which the free alpha-amine attacks the C-terminal carbonyl to give cyclo(Glu-Trp). Goolcharran and Borchardt measured this class of reaction in 1998 and found free-acid dipeptides at pH 4 to 6 among the slower cases, well behind esters and amides. The rate for Glu-Trp free acid specifically has not been measured, so it belongs on the list of open questions rather than the list of established risks.

What is absent matters as well. There is no Asn or Gln, so no amide deamidation. No Met, so no sulfoxide. No Cys, so no disulfide scrambling or thiol oxidation. No Asp-Gly or Asp-Pro motif, so no isoaspartate route. For a molecule of 333.34 Da the degradation map is unusually short, and every item on it traces back to one of the two residues.

The most useful formulation evidence comes from the Russian medicine itself, which is already a solution rather than a powder. It is 100 microgram/ml of the sodium salt in unpreserved saline held at 2-8°C, with a labelled shelf life of 2 years 6 months in the Cytomed presentation. That is a real answer to whether this dipeptide tolerates aqueous storage, and the answer is that a dilute, cold, light-protected solution is formally stable for years. It is not an answer about a solution 30 or more times as concentrated in an undisclosed excipient system, which is what a research pen is.

What Does the Thymogen Pen Deliver Per Increment?

Concentration in the device is 6/3 mg/ml, and because the molecular weight is 333.34 Da the molarity in millimolar is numerically equal to 6 multiplied by 1.000, since the 3 ml and the 3.000 mM per mg/ml cancel exactly.

Worked for a 10 mg fill: 10/3 gives 3.33 mg/ml, which is 10.0 mM. Mass per 0.01 ml, the smallest increment on a standard insulin-graduated barrel, is 6 multiplied by 3.33 microgram, or 33.3 microgram at 10 mg. Per 0.1 ml the figure is 6 multiplied by 33.3 microgram.

Those numbers are worth setting against the published concentrations. The registered Russian injection is 100 microgram/ml, which is 0.30 mM. A 10 mg fill is 33-fold more concentrated, so 0.03 ml of it holds the same mass as a full 1 ml ampoule of the medicine. The single rat lifespan study delivered 5 microgram in 0.2 ml of saline, a working solution of 25 microgram/ml and roughly 133-fold more dilute again. The IM862 oncology trials used 5 to 20 mg per intranasal dose, a route whose exposure cannot be mapped onto a subcutaneous device at all.

Relative to everything in the published record this is a concentrated stock, and serial dilution is the normal step between the device and any reported concentration.

Thymogen Pen vs Vial: What the Format Actually Settles

The thymogen pen vs vial question resolves differently for this compound than for most, because the reference product is a solution and the lyophilized vial is the unusual presentation rather than the default one.

A pen fixes concentration at manufacture and removes reconstitution error. The pen versus vial comparison covers that general case, and the preloaded autoinjector category page covers what the format does to the degradation clock.

What is specific is the tryptophan. A lyophilized vial of the same dipeptide can sit in a freezer for a year with its indole essentially inert, and the photochemistry starts only after reconstitution. A pen has no such quiet period. Cumulative light exposure across every session is a running total from the fill date, which makes the pen the better choice for work concentrated into a short window and the worse choice for a device opened occasionally over many months.

The nasal presentation answers a third question again, since all three IM862 clinical trials used the intranasal route.

Does Thymogen Come in a Pen?

Yes, as a research preparation: this device holds 6mg of the dipeptide in 3 ml of solution, ready to draw. No pen presentation of the registered Russian medicine exists, and the question of whether Thymogen comes in a pen is worth separating into those two answers.

The registered forms are a 1 ml single-use ampoule for intramuscular injection at 100 microgram/ml, a nasal spray at 25 microgram per dose preserved with benzalkonium chloride, and a 0.05 percent cream. Multi-dose devices are not among them, and the ampoule is unpreserved, which is the formulation choice a single-use container permits and a multi-draw cartridge does not.

That difference belongs on the pre-purchase question list, because a cartridge intended for repeated entry either carries an antimicrobial preservative or relies on aseptic technique at every draw.

What the Product Record Does Not State

Four values are absent, and each of them changes how a stored solution behaves.

The excipient system is unpublished. Whether the buffer is acetate, phosphate or citrate is not a detail here: phosphate and citrate are the two systems Chelius and colleagues identified as accelerating N-terminal glutamate cyclisation, so the buffer choice acts directly on the main mass-changing route.

Solution pH is unpublished. Diketopiperazine closure and pyroglutamate formation have different pH optima, and without a number neither rate can be estimated even to an order of magnitude.

The salt form is unpublished. The Russian medicine is the sodium salt; research suppliers ship acetate or TFA. Residual trifluoroacetate matters in cell culture at the concentrations a stock like this reaches, and it is not visible in a purity figure quoted as area percent.

Solution stability over device shelf life is unpublished, and no peer-reviewed forced-degradation study of Glu-Trp was located during research for this page. The 2 year 6 month figure on the Russian label applies to 100 microgram/ml in saline, not to a multi-milligram-per-millilitre research fill.

Verifying the Thymogen Pen and Confirming Its Contents

The tryptophan that makes this compound photo-labile also makes it easy to watch, which is a rare piece of luck among the short bioregulator peptides.

Absorbance at 280 nm is available here and is not available for Epithalon, Cartalax or any of the other peptides in the family that contain no aromatic residue. A dilution measured against buffer gives a concentration check that takes minutes. More usefully, the photoproducts absorb where the parent does not: kynurenine and N-formylkynurenine extend absorbance into the near-ultraviolet above 320 nm, and both are fluorescent. A shoulder appearing above 320 nm in a stored device is a direct signal that indole oxidation has been running.

Mass spectrometry covers the other route but with a trap in it. Pyroglutamyl-tryptophan and cyclo(Glu-Trp) both lose exactly 18 Da from the linear dipeptide, so the [M+H]+ signal moves from 334.14 to 316.13 for either. The two products are isobaric and a mass shift alone cannot separate them. Chromatographic retention can, and the two elute at different times on a standard reversed-phase gradient, so identification needs the LC as well as the MS.

Inspect the solution against a white background before each draw. It should be clear and colourless with no particulate. Yellowing is consistent with accumulated kynurenine-type products, which is the one visible endpoint this compound offers.

What the Glu-Trp Literature Actually Reports

The clinical file on this molecule is larger than for any other Khavinson-school peptide and it is mostly negative, because the same dipeptide was developed in the West as the oncology candidate IM862, or oglufanide, by Cytran.

Tulpule and colleagues reported in 2000 a randomised two-schedule study of IM862 nasal solution at 5 mg in 44 patients with AIDS-related Kaposi sarcoma, with 36 percent major responses and no placebo arm. The phase 3 that followed settled the question. Noy and colleagues randomised 202 patients in 2005 and found a response rate of 23 percent against 21 percent for placebo (P = 0.46), with a shorter median time to progression on the drug: 16 weeks against 35 weeks (P = 0.012). Deplanque and colleagues gave 20 mg intranasally three times daily to 25 patients with metastatic renal cell carcinoma in 2004 and recorded no objective responses; development stopped there.

The animal record points the other way and rests on one experiment. Anisimov, Khavinson and Morozov injected 76 female outbred rats with 5 microgram of L-Glu-L-Trp subcutaneously five times a week for twelve months from five months of age. Survival of the last 10 percent rose from 949 to 1048 days, the Gompertz ageing-rate parameter fell from 0.0071 to 0.0041 per day, total tumour incidence was 1.5-fold lower and haematopoietic malignancy 3.4-fold lower. It has not been replicated.

In vitro, Avolio and colleagues found in 2022 that this dipeptide was the most effective of five Khavinson peptides at attenuating IL-17 release from activated THP-1 macrophages. The group’s own proposal that these peptides bind DNA at GGAG motifs is an in silico and in vitro hypothesis without independent replication. A summary of the immune-cell work and the bioregulator research overview place it in context.

No human pharmacokinetic study exists; the Russian label states only that the compound is hydrolysed to L-glutamic acid and L-tryptophan. Adverse findings on record are mild transient headache, fatigue, tingling and nausea (Tulpule 2000), grade 1 to 2 sinusitis and headache (Deplanque 2004), and the shorter time to progression in the 2005 phase 3.

Thymogen Pen Storage and the Clock It Starts

Thymogen pen storage is 2-8°C, dark, and never frozen, and the reason for each of those three is different for this molecule than for a generic peptide.

Refrigeration slows both cyclisation routes, which are thermally driven. Darkness addresses the indole, which is the fast route and the one least sensitive to temperature. Freezing is the instruction most often ignored: freeze-concentration pushes solute and buffer species into a shrinking unfrozen fraction, raising local concentration and driving pH excursions, which is the condition that accelerates diketopiperazine closure and pyroglutamate formation.

Published thymogen solution stability data does not exist at research concentrations, and that gap should be stated rather than papered over with the Russian label figure. What can be said about thymogen solution stability is that the same molecule survives 2 years 6 months at 100 microgram/ml under refrigeration in saline, that no forced-degradation study has been published at any concentration, and that the pen’s own excipients and pH are undisclosed. Record the fill date, the date of first actuation, and cumulative time out of the refrigerator, and treat those as experimental variables rather than logistics.

What Is the Safety and Regulatory Position?

This dipeptide is approved as a medicine in one country only. Thymogen (alpha-glutamyl-tryptophan sodium) is registered in Russia as an immunostimulant under ATC code L03AA, with Cytomed of St Petersburg as authorisation holder and a further injection registration held by OOO Company DEKO, revised 5 March 2023. This research preparation is not that medicine: different concentration, different container, different salt form and no marketing authorisation anywhere.

The FDA, EMA, PMDA, TGA and Health Canada have approved nothing containing this compound. The Western IM862 programme ended after the negative phase 3 without an application. The molecule is not named on the WADA 2026 Prohibited List, whose S2 class names thymosin-beta4 rather than Glu-Trp. It does not appear on the FDA 503B category lists published 21 March 2025, has no USP monograph and is not an approved-drug component, so it is outside section 503A eligibility.

One identity point carries regulatory weight. The isomers gamma-D-Glu-L-Trp (golotimod, SCV-07) and iso-Glu-D-Trp (Thymodepressin) both reached clinical development and are different molecules with different pharmacology, so the alpha, L,L designation on a certificate of analysis is load-bearing rather than decorative.

Russian label contraindications are hypersensitivity and age under one year. No controlled Western trial has studied injected Glu-Trp for any immune indication, and the only placebo-controlled trial of the molecule in any form was negative. The device is for laboratory research, and its contents must not be administered to humans or animals.

What Is the Proposed Mechanism of Action for Glu-Trp?

The stated mechanism for this dipeptide is regulation of T-cell differentiation in the thymus gland, and the claim descends from the extract it replaced. Thymalin, a preparation of bovine thymus, was the parent product in Khavinson’s programme, and L-glutamyl-L-tryptophan was synthesised as a defined two-residue stand-in for whatever in Thymalin was active. Reports describe increased maturation of T-lymphocytes in culture and changes in circulating lymphocyte subsets in treated animals.

Gene expression is the level at which the effect is proposed to act, in common with every other member of this family. What has not been demonstrated for Glu-Trp is that the intact dipeptide reaches a lymphocyte nucleus after injection, and a two-residue peptide is a ready substrate for serum peptidases. The active ingredient is well defined chemically and poorly defined pharmacologically, which is an unusual combination and worth stating plainly.

Thymalin itself remains the better-documented preparation of the two. It has a Russian registration and a longer clinical record, and much of what is written about the synthetic dipeptide is really about Thymalin. Anyone comparing the two should know that Thymalin is a mixture from tissue and this is a single defined molecule, so results from one do not transfer to the other by default.

How Does This Compare With Thymosin Alpha-1?

Thymosin alpha-1 is the compound most often confused with this one, and it is a different order of thing. It is a 28-residue acetylated peptide, originally isolated from thymic tissue, marketed as thymalfasin under the brand Zadaxin, and approved in more than thirty countries for hepatitis B, hepatitis C and as a vaccine adjuvant, though not in the United States or the European Union, where it holds orphan designations only. It has registrational trials, a label, an adverse event profile and a defined receptor interaction through Toll-like receptor signalling.

Glu-Trp has none of those things. Both are described as thymic peptides and as immunomodulator candidates, and the resemblance ends at the category. Where that molecule has a pharmacology, this dipeptide has a research programme. Listing them together as immune support options presents a licensed medicine and an uncharacterised research compound as equivalent choices, which they are not.

The wider vocabulary needs the same care. Immune balance and immune resilience are marketing terms rather than measurable endpoints, and none appears as a defined outcome in the published work on this molecule. Immunosenescence, the age-related decline in immune system function, is a real and well-studied phenomenon, and it is the phenomenon this compound is nominated against rather than one it has been shown to affect. Claims about anti-aging, cellular repair and tissue repair for Glu-Trp are extrapolations from the family, not findings about this peptide. No study of this dipeptide has measured cellular repair by any method.

What Should Be on the Certificate, and What Does the Format Change?

Tryptophan makes this certificate different from the others in the catalogue. It is the one residue here that absorbs strongly at 280 nm, so a UV purity check actually works for this compound, and it is also the residue most easily oxidised and most easily destroyed by light. A CoA for this material should report purity by HPLC with detection at both 214 and 280 nm, and CoAs that give only one wavelength are reporting half the picture, an accurate mass, water content and the counter-ion. Oxidation products sit sixteen and thirty-two daltons above the parent and are detectable if anyone looks.

A Thymogen vial ships as a lyophilized powder and is reconstituted with bacteriostatic water at the bench, which lets the dry material be stored cold and dark until it is needed. This pen ships in solution, so the tryptophan has been in water and in contact with dissolved oxygen since the fill date, and that date is not on the product record. Ask for it. For a research peptide whose most reactive residue is also its chromophore, the fill date is the single most informative number a supplier can provide, and it is worth more than the purity figure printed beside it.

Two final distinctions. This is a dipeptide, not a tetrapeptide: the four-residue members of this family, Testagen and Cortagen among them, have different chemistry and different degradation routes, and their stability data does not transfer. And this is a peptide bioregulator in the Khavinson sense rather than a treatment. It is supplied for laboratory research, no regulator has approved it, and peptide therapy providers listing it beside BPC-157 or an approved thymic medicine are grouping by claimed effect rather than by evidence.

Published Literature

Every entry below was checked against the publisher record or a primary index during research for this page. None of them concerns a pen or a multi-milligram solution.

1. 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):55-59. DOI: 10.1023/A:1010042008969
2. 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. Journal of Clinical Oncology. 2000;18(4):716-723. PMID: 10673512
3. 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. Journal of Clinical Oncology. 2005;23(5):990-998. PMID: 15598977
4. Deplanque G, Madhusudan S, Jones PH, et al. Phase II trial of the antiangiogenic agent IM862 in metastatic renal cell carcinoma. British Journal of Cancer. 2004;91(9):1645-1650. DOI: 10.1038/sj.bjc.6602126
5. Avolio F, Martinotti S, Khavinson VK, et al. Peptides regulating proliferative activity and inflammatory pathways in the monocyte/macrophage THP-1 cell line. International Journal of Molecular Sciences. 2022;23(7):3607. PMID: 35408963
6. Pattison DI, Rahmanto AS, Davies MJ. Photo-oxidation of proteins. Photochemical and Photobiological Sciences. 2012;11(1):38-53. DOI: 10.1039/c1pp05164d
7. Chelius D, Jing K, Lueras A, et al. Formation of pyroglutamic acid from N-terminal glutamic acid in immunoglobulin gamma antibodies. Analytical Chemistry. 2006;78(7):2370-2376. DOI: 10.1021/ac051827k
8. Goolcharran C, Borchardt RT. Kinetics of diketopiperazine formation using model peptides. Journal of Pharmaceutical Sciences. 1998;87(3):283-288. DOI: 10.1021/js970325m

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