Thymulin

Dosing from the Literature

Published for immunity: 1, 5 and 10 mg a day in two randomized trials in rheumatoid arthritis, and 10 µg/kg every three days in four adults with cancer. Not published: a dose for anyone without a diagnosed condition, and any human dose since the 1980s.

No regulator has approved a dose. Each row below is the dose one published study used, with who or what it was given to.

What It Is

Thymulin is a small zinc-dependent nonapeptide (a chain of 9 amino acids) hormone produced by thymic epithelial cells (TECs). Its structure is the peptide pGlu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn with a single zinc(II) ion bound to it (Cung et al., 1988). Without that zinc the peptide is biologically inactive, and adding zinc salts restores the activity, best at one zinc ion per peptide (Dardenne et al., 1982).

The peptide was first isolated by Jean-François Bach and colleagues in Paris in 1975 from porcine and human serum, where they named it "facteur thymique sérique" (FTS — serum thymic factor). The name "thymulin" (FTS-Zn) was proposed for the zinc-bound form by Dardenne, Bach and colleagues in 1982, once the zinc dependence was established (Dardenne et al., 1982). Bach's group continued thymulin research at the Hôpital Necker for the next two decades, generating most of the foundational immunology characterizing the molecule's role in T-cell maturation and immune-system regulation.

Thymulin sits at a specific point in the immune system: it is one of several thymic peptides (alongside thymosin α1, thymopoietin, thymic humoral factor, and others) that mediate the thymic contribution to T-cell development and peripheral immune balance. It is mechanistically distinct from these other thymic peptides — different sequence, different receptor footprint, different downstream effects. The clinical and research interest in thymulin is concentrated in two areas: immune restoration in immunodeficient or aged subjects (where thymic output declines), and zinc deficiency contexts (where bioactive zinc-bound thymulin is among the first measurable casualties of insufficient zinc status).

In the modern peptide community, thymulin is rare. It has not achieved the popularity of thymosin α1 or the Khavinson "Thymalin" preparation despite cleaner pharmacology, in part because no commercial pharmaceutical product has ever been brought to market and because the zinc-dependence makes consistent supply more complex than for unmodified peptides. Much current lay discussion of "thymulin" actually refers to "Thymalin" — the Khavinson polypeptide-complex extract from calf thymus that is molecularly, mechanistically, and regulatorily distinct from Bach's nonapeptide.

Mechanism of Action

Thymulin's mechanism is built around its dual immunomodulatory (adjusting the immune system up or down) and zinc-dependent character. Zinc binding is not incidental: the zinc-free peptide is inactive in the rosette assay, and adding zinc salts restores the activity, best at one zinc ion per peptide (Dardenne et al., 1982; PMID 6957870).

• Zinc-dependent activation — The apopeptide (zinc-free thymulin) is inactive, and zinc restores the activity (Dardenne et al., 1982; PMID 6957870). Gel filtration found the nonapeptide binds one zinc ion, apparent K_d 5 ± 2 × 10⁻⁷ M at pH 7.5, with no binding below pH 6.0 (Gastinel et al., 1984; PMID 6538097). NMR of the Zn(II) complex found two species, 1:1 and 1:2, with the 1:1 the only conformation the antibodies recognized (Cung et al., 1988; PMID 3356698).
• T-cell maturation — Thymulin is described as playing a part in thymocyte differentiation (Okamoto et al., 1993; PMID 8407057), and reviews group it with thymosin α1 and thymopoietin as thymic hormones reported to act on both prothymocytes and mature T-cells in the periphery, keeping them committed to the T-cell system (Hadden et al., 1992; PMID 1485720).
• Regulatory rather than purely immunostimulatory — In restraint-stressed mice 1 ng/kg restored antibody production, while 1 ng–1 µg/kg left normal mice unchanged; the authors concluded that thymulin normalizes altered responses (Okamoto et al., 1993; PMID 8407057). In four cancer patients given 10 µg/kg intravenously, natural-killer activity rose in the two whose values were low and fell in the two whose values were normal or high (Dokhelar et al., 1983; PMID 6195118).
• Anti-inflammatory / CNS activity — A review by the Goya group describes thymulin and a synthetic analog as anti-inflammatory and analgesic peptides in the brain and other organs in animal models (Reggiani et al., 2014; PMID 24588820).
• Zinc–thymulin axis — Zinc deficiency lowers bioactive thymulin, which makes it a measure of zinc status. In old mice, zinc supplementation restored serum thymulin activity along with thymocyte numbers and thymic thickness; in zinc-supplemented people — elderly, Down's syndrome, older patients with infections — thymic endocrine activity recovered (Mocchegiani et al., 2013; PMID 22222917).
• Steroid suppression — Adrenal steroids act directly on thymic epithelial cells to inhibit thymulin secretion (Goya et al., 2007; PMID 17389714).
• Pituitary / hormonal interaction — Thymulin production and secretion are stimulated directly by growth hormone and prolactin and indirectly by thyrotropin through thyroid hormones, and inhibited by adrenal and gonadal steroids (Goya et al., 2007; PMID 17389714).
• Reciprocal pituitary feedback — In dispersed anterior pituitary cells from young, middle-aged and senescent female rats, thymulin released prolactin and TSH, with less release from the senescent cells (Brown et al., 1998; PMID 9818729). The feedback loop this suggests has been shown in cells and in mice, not in people.
• Pain / peripheral inflammation modulation — The study cited here gave rats systemic zinc, not thymulin: 20 nmol reduced hyperalgesia and the rise in IL-1β and NGF in an inflamed hindpaw (Safieh-Garabedian et al., 1996; PMID 8887968). The same group's thymulin work is covered in the Goya-group review (Reggiani et al., 2014; PMID 24588820).
• Gene-therapy restoration — Reggiani, Hereñú et al. (Gene Ther 2006; PMID 16617301) demonstrated thymulin gene therapy can restore circulating thymulin in thymectomized animals, validating the peptide-as-hormone framework.
• Receptor — characterization gap — No named cell-surface receptor for thymulin appears in the papers cited here after 50 years. What they measure is function: restoration of rosette formation in a bioassay (Dardenne et al., 1982; PMID 6957870; Goya et al., 2007; PMID 17389714). Its effect on rat pituitary cells was called receptor-mediated, involving calcium, cAMP and inositol phosphates, without a receptor being named (Brown et al., 1998; PMID 9818729).
• Hypothalamic-pituitary-thymic axis — The traffic runs both ways in the animal work: pituitary hormones change thymulin secretion by thymic epithelial cells, and quenching thymulin in newborn mice lowered their LH and FSH at 33 and 45 days, which thymulin gene therapy prevented in athymic mice (Goya et al., 2007; PMID 17389714).
• Zinc kinetic biology — NMR showed the zinc complexation is a fast exchange on the NMR time scale (Cung et al., 1988; PMID 3356698), and binding falls with pH and is competed for by other metal ions — gallium, aluminum, manganese and copper (Gastinel et al., 1984; PMID 6538097). A loosely held cofactor is why the measure tracks zinc status.

What the Research Shows

Thymulin has one of the longer histories of any peptide on this site, and most of it is old: PubMed indexes 496 papers with thymulin or serum thymic factor in the title or abstract — 29 in the 1970s, 164 in the 1980s, 158 in the 1990s, 88 in the 2000s, 46 in the 2010s and 12 since 2020 (counted October 2026). The clinical work was done by the Bach and Dardenne group and their collaborators.

• Discovery (Bach & Dardenne, 1975–1982) — Isolated as FTS, the serum thymic factor (Bach et al., 1975); renamed thymulin when the zinc dependence was established (Dardenne et al., 1982; PMID 6957870).
• Zinc binding (Gastinel et al., BBA 1984; PMID 6538097) — Established 1:1 Zn²⁺ binding and conformational basis of activity.
• NMR structure (Cung et al., J Biol Chem 1988; PMID 3356698) — NMR of Zn(II)-nonapeptide complex confirmed structural model.
• Zinc contribution (Dardenne et al., PNAS 1982; PMID 6957870) — Contribution of zinc and other metals to biological activity of the serum thymic factor.
• Stress-induced antibody rescue (Okamoto et al., 1993; PMID 8407057) — Three days of thymulin at 1 ng/kg restored thymus-dependent antibody production in restraint-stressed mice, whose response had fallen to about half of normal; 1 ng–1 µg/kg changed nothing in normal mice.
• Aging immune decline — Circulating thymulin falls with normal aging (Goya et al., 2007; PMID 17389714), as the thymic hormones generally do, alongside the age-related decline of cell-mediated immunity (Hadden et al., 1992; PMID 1485720).
• Zinc deficiency — In old mice, zinc supplementation restored serum thymulin activity, thymocyte numbers and the thickness of the thymus; in zinc-supplemented elderly and Down's syndrome subjects, thymic endocrine activity recovered (Mocchegiani et al., 2013; PMID 22222917).
• HIV: measured, not given — Circulating thymulin falls sharply in people with AIDS and in DiGeorge syndrome, and with normal aging (Goya et al., 2007; PMID 17389714). No study has given thymulin to people with HIV.
• Childhood immunodeficiency (Bordigoni et al., 1982; PMID 6124716) — One report, on three children with IgA and IgE deficiency and T-cell defects given synthetic FTS intravenously: fewer and milder infections, better cell-mediated immunity tests, and serum IgA where there had been none. It went no further.
• Neuroendocrine-immune review framework (Reggiani et al., Curr Pharm Des 2014; PMID 24588820) — Modern review characterizing thymulin's role in the neuroendocrine-immune axis.
• Gene-therapy proof-of-principle (Reggiani et al., Gene Ther 2006; PMID 16617301) — Long-term restoration of circulating thymulin in thymectomized mice and rats.
• Bach-group Necker corpus — Jean-François Bach, Mireille Dardenne, Jean-Marie Pleau, and colleagues produced the foundational thymulin literature over approximately 20 years at Hôpital Necker in Paris. The body of work spans isolation, zinc-dependence characterization, structure-activity relationship studies, receptor binding work on T-cell precursors, and clinical pilot administration across immunodeficiency indications. This corpus is the primary scientific record for thymulin biology.
• Safieh-Garabedian pain / inflammation axis — The paper cited for this on Kalios gave rats zinc, not thymulin, and found 20 nmol reduced hyperalgesia and the rise in IL-1β and NGF in an inflamed hindpaw (Safieh-Garabedian et al., 1996; PMID 8887968). The group's later work on thymulin and a thymulin-related peptide as analgesics in animals is covered in the Goya-group review (Reggiani et al., 2014; PMID 24588820).
• Goya / Reggiani neuroendocrine extensions — Argentine groups developed thymulin gene-therapy models and characterized the reciprocal feedback between thymulin and the anterior pituitary (prolactin, TSH). Situates thymulin within the broader neuroendocrine-immune axis.
• Zinc-thymulin biomarker use — Serum thymulin activity has been used as a measure of zinc status: it fell with mild zinc deficiency and came back with zinc supplementation (Mocchegiani et al., 2013).

Human Data

Human evidence for thymulin spans 50 years and is mostly measurement of the body's own thymulin, with a handful of small studies that gave it, three of them randomized and placebo-controlled, all from the 1980s:

• Endogenous thymulin pharmacology (1970s–80s) — Bach group characterized serum thymulin across age, immunodeficiency, zinc status, and endocrine perturbations.
• Zinc–thymulin axis in humans — In zinc-deficient people, bioactive thymulin is low and comes back with zinc supplementation; in elderly and Down's syndrome subjects given zinc, thymic endocrine activity recovered (Mocchegiani et al., 2013).
• Children with immunodeficiency — Three children with IgA and IgE deficiency and T-cell defects were given synthetic FTS intravenously: infections grew less frequent and less severe, cell-mediated immunity tests improved, and serum IgA appeared within 4 weeks in the two who had none. Stopping it reversed the improvement, which returned when it was restarted (Bordigoni et al., 1982). Three patients, open-label, no control group.
• Aging studies — Circulating thymulin falls with normal aging (Goya et al., 2007), as the thymic hormones generally do, alongside the decline of cell-mediated immunity (Hadden et al., 1992).
• Cancer patients — Four adults were given 10 µg/kg intravenously every 3 days; natural-killer activity rose in the two whose values were low beforehand and fell in the two whose values were normal or high (Dokhelar et al., 1983).
• Randomized trials, then nothing — Two randomized, double-blind, placebo-controlled trials in rheumatoid arthritis compared 1, 5 and 10 mg a day: 5 mg was the most effective, with 56% of patients improved on the global assessment against 17% on placebo (Amor et al., 1987). A randomized, double-blind, placebo-controlled trial in 40 people with multiple sclerosis, 6 months of subcutaneous dosing, found no difference from placebo (Roullet et al., 1989). No thymulin trial has been registered on ClinicalTrials.gov since.

Reconstitution & Storage

Thymulin is sold as a lyophilized powder for laboratory use. No label, monograph or published guide says how to mix or store it outside a laboratory, so the table below is arithmetic and nothing more.

• Zinc binding — In one published protocol the synthetic peptide was mixed with an equal molar amount of zinc chloride in phosphate-buffered saline 30 minutes before it was injected into mice (Goya et al., 2007). Binding is pH-dependent: one zinc ion per peptide, with an apparent K_d of 5 ± 2 × 10⁻⁷ M at pH 7.5 and no binding below pH 6.0 (Gastinel et al., 1984).
• Storage — No label, monograph or published study gives a storage temperature or a shelf life for thymulin, mixed or dry.
• Activity verification — Published work measures bioactive thymulin with a rosette bioassay: the peptide restores rosette formation in spleen cells from thymectomized mice (Goya et al., 2007).

→ Calculator — vial-to-syringe math

Side Effects & Risks

The trials that gave it to people reported little: minimal adverse effects in the rheumatoid-arthritis trials (Amor et al., 1987) and no significant side effects over 6 months of subcutaneous dosing in the 40-patient multiple-sclerosis trial (Roullet et al., 1989). Those are the whole safety record in people, and both were run in the 1980s.

• Autoimmune disease — Both randomized trials were run in autoimmune disease, rheumatoid arthritis and multiple sclerosis, and reported minimal or no side effects (Amor et al., 1987; Roullet et al., 1989). No flare was reported in either.
• Zinc balance — A 5 mg dose of the zinc-bound nonapeptide carries about 0.4 mg of zinc, one zinc ion per 857 Da of peptide, against the 10–12 mg a day a review of zinc in the elderly calls a physiological intake (Mocchegiani et al., 2013).
• Pregnancy and lactation — No study in pregnancy or lactation is published.
• Cancer — The one study in cancer patients gave 10 µg/kg intravenously every 3 days to four adults: natural-killer activity rose in the two whose pre-treatment values were low and fell in the two whose values were normal or high (Dokhelar et al., 1983).
• Drug interactions — None studied. Adrenal steroids inhibit thymulin secretion by thymic epithelial cells in animals (Goya et al., 2007); nothing is published on giving thymulin alongside a steroid or an immunosuppressant.
• Purity and zinc binding — The zinc-free peptide is inactive in the rosette assay the molecule was defined by (Dardenne et al., 1982), so a purity figure does not show whether what is in a vial is the active, zinc-bound form.
• WADA status — Not named on the Prohibited List, but prohibited at all times under S0, non-approved substances, because no government has approved it for human therapeutic use (WADA Prohibited List 2026).
• Long-term safety unknown — The longest published human exposure is 6 months, in the 40-patient multiple-sclerosis trial, which recorded no significant side effects (Roullet et al., 1989). Nothing longer, and nothing in healthy people, is published.

Bloodwork & Monitoring

No trial, label or guideline sets monitoring for thymulin. The published studies measured what each was studying: clinical scores and T-cell subsets in the rheumatoid-arthritis trials (Amor et al., 1987), natural-killer-cell activity in the four cancer patients (Dokhelar et al., 1983), cell-mediated immunity tests and serum IgA in the three children given it intravenously (Bordigoni et al., 1982), and serum thymulin against zinc status in zinc-deficient people (Mocchegiani et al., 2013). Serum thymulin itself is measured by a research bioassay (Goya et al., 2007), not by a clinical laboratory test.

Quick Compare — Thymulin vs Thymalin vs Thymosin α1 vs Thymosin β4

Thymulin is often confused with other thymic-derived peptides. Clear comparison:

• Thymulin vs Thymalin — Different molecules entirely. Thymulin is Bach's zinc-bound nonapeptide; Thymalin is Khavinson's polypeptide-extract preparation. Most lay usage of "thymulin" actually refers to "Thymalin."
• Thymulin vs Thymosin α1 — Different peptides, different mechanisms, different clinical statuses. Thymosin α1 is approved in many countries for hepatitis adjunct therapy with a much larger clinical evidence base.
• Thymulin vs thymosin β4 — Both are tied to the thymus: thymulin is made by thymic epithelial cells (Okamoto et al., 1993), and thymosin β4 was sequenced from calf thymus (Low et al., 1981). Thymosin β4 turned out to be in almost every cell, where it binds actin (Huff et al., 2001), and TB-500 is a synthetic seven-amino-acid piece of it that no published study has given to people (FDA TB-500 review, 2026); thymulin is described as playing a part in thymocyte differentiation (Okamoto et al., 1993).

→ See Thymalin profile  •  → See Thymosin α1 profile  •  → See Thymosin β4 profile  •  → See TB-500 profile

Commonly Stacked With

No published study gives thymulin together with another peptide in people.

Stacking this? Read the receipt →

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Legal Status

Related Compounds

Thymic and immune peptides that come up alongside Thymulin:

Next Steps

References

1. Bach JF, Dardenne M, Pleau JM, Bach MA. Isolation, biochemical characteristics, and biological activity of a circulating thymic hormone in the mouse and in the human. Ann N Y Acad Sci. 1975;249:186-210. PMID: 1079427.
2. Dardenne M, Pleau JM, Nabarra B, Lefrancier P, Derrien M, Choay J, Bach JF. Contribution of zinc and other metals to the biological activity of the serum thymic factor. Proc Natl Acad Sci USA. 1982;79(17):5370-5373. PMID: 6957870.
3. Gastinel LN, Dardenne M, Pleau JM, Bach JF. Studies on the zinc binding site to the serum thymic factor. Biochim Biophys Acta. 1984;797(2):147-155. PMID: 6538097.
4. Cung MT, Marraud M, Lefrancier P, Dardenne M, Bach JF, Laussac JP. NMR study of a lymphocyte differentiating thymic factor. An investigation of the Zn(II)-nonapeptide complexes (thymulin). J Biol Chem. 1988;263(12):5574-5580. PMID: 3356698.
5. Okamoto M, Morishita M, Setoguchi C, Nakata K. Restorative effect of short term administration of thymulin on thymus-dependent antibody production in restraint-stressed mice. Int J Immunopharmacol. 1993;15(6):757-762. PMID: 8407057. DOI: 10.1016/0192-0561(93)90149-s.
6. Reggiani PC, Schwerdt JI, Console GM, Roggero EA, Dardenne M, Goya RG. Physiology and therapeutic potential of the thymic peptide thymulin. Curr Pharm Des. 2014;20(29):4690-4696. PMID: 24588820.
7. Reggiani PC, Hereñú CB, Rimoldi OJ, et al. Gene therapy for long-term restoration of circulating thymulin in thymectomized mice and rats. Gene Ther. 2006;13(15):1214-1221. PMID: 16617301.
8. Goya RG, Reggiani PC, Vesenbeckh SM, et al. Thymulin gene therapy prevents the reduction in circulating gonadotropins induced by thymulin deficiency in mice. Am J Physiol Endocrinol Metab. 2007;293(1):E182-E187. PMID: 17389714.
9. Brown OA, Sosa YE, Bolognani F, Goya RG. Thymulin stimulates prolactin and thyrotropin release in an age-related manner. Mech Ageing Dev. 1998;104(3):249-262. PMID: 9818729.
10. Safieh-Garabedian B, Poole S, Allchorne A, Kanaan S, Saadé NE, Woolf CJ. Zinc reduces the hyperalgesia and upregulation of NGF and IL-1β produced by peripheral inflammation in the rat. Neuropharmacology. 1996;35(5):599-603. PMID: 8887968.
11. Cunningham-Rundles S, et al. Zinc, infection, and immunity. Ann N Y Acad Sci. 1998;842:53-60.
12. Mocchegiani E, Romeo J, Malavolta M, Costarelli L, Giacconi R, Diaz LE, Marcos A. Zinc: dietary intake and impact of supplementation on immune function in elderly. Age (Dordr). 2013;35(3):839-860. PMID: 22222917.
13. Khavinson VKh, Morozov VG. Peptides of pineal gland and thymus prolong human life. Neuro Endocrinol Lett. 2003;24(3-4):233-240. PMID: 14523363.
14. Hadden JW, Malec PH, Coto J, Hadden EM. Thymic involution in aging. Prospects for correction. Ann N Y Acad Sci. 1992;673:231-239. PMID: 1485720.
15. Hadden JW. The treatment of zinc deficiency is an immunotherapy. Int J Immunopharmacol. 1995;17(9):697-701. PMID: 8582781.
16. FDA. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the FD&C Act (503A categories list), versions updated April 15, April 22 and May 14, 2026. fda.gov/media/94155/download. Read October 3, 2026. (Notice that 12 peptides would leave Category 2 because their nominations were withdrawn; their removal; GHK-Cu, except injectable, back in Category 1.)
17. Amor B, Dougados M, Mery C, Dardenne M, Bach JF. Nonathymulin in rheumatoid arthritis: two double blind, placebo controlled trials. Ann Rheum Dis. 1987;46(7):549-554. PMID: 3310925.
18. Roullet E, Cesaro P, Simon-Lavoine N, Degos JD, Marteau R. Nonathymulin treatment of multiple sclerosis: double-blind pilot study. Acta Neurol Scand. 1989;80(6):575-578. PMID: 2618585.
19. Dokhelar MC, Tursz T, Dardenne M, Bach JF. Effect of a synthetic thymic factor (facteur thymique serique) on natural killer cell activity in humans. Int J Immunopharmacol. 1983;5(4):277-282. PMID: 6195118.
20. Bordigoni P, Faure G, Bene MC, Dardenne M, Bach JF, Duheille J, Olive D. Improvement of cellular immunity and IgA production in immunodeficient children after treatment with synthetic serum thymic factor (FTS). Lancet. 1982;2(8293):293-297. PMID: 6124716.
21. World Anti-Doping Agency. Prohibited List 2026 (in effect January 1, 2026). S0, Non-approved substances. wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf. Read October 3, 2026.
22. 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. PMID: 6940133. DOI: 10.1073/pnas.78.2.1162.
23. Huff T, Müller CS, Otto AM, Netzker R, Hannappel E. beta-Thymosins, small acidic peptides with multiple functions. Int J Biochem Cell Biol. 2001;33(3):205-220. PMID: 11311852. DOI: 10.1016/s1357-2725(00)00087-x.
24. Safer D, Elzinga M, Nachmias VT. Thymosin beta 4 and Fx, an actin-sequestering peptide, are indistinguishable. J Biol Chem. 1991;266(7):4029-4032. PMID: 1999398.
25. FDA. FDA Evaluation of TB-500-Related Bulk Drug Substances (TB-500 (Free Base) and TB-500 acetate). Pharmacy Compounding Advisory Committee briefing document for the meeting of July 23–24, 2026 (memorandum dated May 15, 2026). fda.gov/media/193349/download. Read October 4, 2026.
26. RegeneRx Biopharmaceuticals, Inc. Annual report (Form 10-K) for the fiscal year ended December 31, 2022, filed April 11, 2023. sec.gov/Archives/edgar/data/707511/000141057823000628/rgrx-20221231x10k.htm. Read October 4, 2026.
27. ClinicalTrials.gov. Study of Thymosin Beta 4 in Patients With Venous Stasis Ulcers. NCT00832091. (Results posted.)
28. ClinicalTrials.gov. Safety and Efficacy Study of Thymosin Beta 4 in Patients With Acute Myocardial Infarction. NCT05485818.
29. FDA. Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act (categories 1–3). Updated March 21, 2025. fda.gov/media/94164/download.
30. FDA. Drugs@FDA through openFDA (api.fda.gov/drug/drugsfda.json): searches for thymosin, thymosin beta 4 and timbetasin, October 4, 2026 (no records).

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