Thymulin

Also known as Serum thymic factor (FTS) · Facteur thymique serique · Zinc-FTS · Circulating thymic factor · Thymuline · Thymulin acetate

Not approved — research use onlyCPreclinical research What this means

Thymulin is a nonapeptide produced by thymic epithelial cells whose biological activity exists only when the peptide is bound to zinc; it is studied as a biomarker of zinc and thymic status and in animal models of inflammation, with no approved drug use.

US status: Not approved — research use only
Evidence: Grade C
Half-life: Not located in the sources reviewed for any species.
Class: Zinc-bound thymic nonapeptide hormone (metallopeptide)

Studied in: Immune research · Class: Thymic peptides

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Key takeaways

Thymulin is the zinc-bound form of the thymic nonapeptide FTS: biological activity is strictly zinc-dependent, and the zinc-coupled molecule has a distinct conformation recognised by antibodies that ignore the zinc-free peptide ^2,10.
Its most firmly established use is as a biomarker. Serum thymulin activity was 61% lower in rats on restricted zinc, more sensitive than four other zinc-status measures ^3, and it has been used as a proxy for thymic size and function in children ^5.
Reported anti-inflammatory effects converge on NF-kappaB: in alveolar epithelial cells thymulin reduced endotoxin-induced IL-1beta release and NF-kappaB nuclear translocation ^4, and in aged mice it suppressed myeloid pro-inflammatory cytokine production through NF-kappaB inhibition ^1.
Animal models cover inflammatory pain, chronic septic inflammation, experimental autoimmune encephalomyelitis, type 1 diabetes models and allergic asthma gene therapy; no human treatment trial was identified ^1,6,7,8,9.
No approved use exists; "Thymulin acetate" sits in Category 3 of FDA's 503A bulk substances list, nominated without adequate support ^12,13.

Development stage

Where Thymulin sits between laboratory work and regulatory approval.

Preclinical (current)
Animal and cell work
Phase 1
First human safety studies
Phase 2
Early efficacy signal
Phase 3
Confirmatory trials
Approved
Cleared by a regulator

Stage comes from the regulatory record and ClinicalTrials.gov studies naming the compound (for compounds approved nowhere, only completed trials or trials with posted results count) (checked 2026-10-24). A registered trial is not a result.

Mechanism of action

Thymulin is the nonapeptide pGlu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn complexed with zinc ^10,11. NMR work on the Zn(II)-nonapeptide complex and immunological work with monoclonal antibodies both indicate that the zinc-bound molecule adopts a specific conformation, and that activity is lost without the metal, so zinc is part of the active entity rather than a cofactor added later ^2,10.

Reported actions

Inflammatory signalling: in fetal alveolar type II epithelial cells, thymulin reduced endotoxin-induced IL-1beta release, raised cAMP, and reduced nuclear translocation and DNA binding of NF-kappaB subunits, with zinc contributing independently ⁴.
Myeloid ageing: in aged mice, thymulin was identified as a circulating factor that declines with age and restrains pro-inflammatory cytokine production by myeloid cells through NF-kappaB inhibition, with reported effects on antitumour T-cell responses ¹.
Neuroendocrine links: reviews describe thymulin as a hypophysiotropic peptide interacting with the neuroendocrine system, and a synthetic analogue (metFTS) has been expressed from adenovectors in gene-therapy experiments ⁶.
Nociception: in a rat inflammatory pain model, thymulin treatment was associated with attenuated pain behaviour and changes in spinal signalling pathways ⁷.

Zinc dependence as a measurement problem

Because activity requires zinc, assays of "thymulin activity" in serum partly report zinc status; this is why thymulin activity tracks marginal zinc restriction more sensitively than serum zinc itself in rats ³.

Molecular structure

PubChem CID 71300623 ↗

2D depiction generated from the PubChem record. Depictions are schematic and do not show salt form, counter-ions or conformation.

Formula: C33H54N12O15
Molecular weight: 858.9 g/mol
CAS: 78922-62-0
InChIKey: LIFNDDBLJFPEAN-YTAPOSPOSA-N

Research overview

Human research

No human treatment trial was identified in the sources reviewed. Human work is observational and uses thymulin as a biomarker: in 290 children aged 9 to 13 years born to participants in a maternal vitamin A or beta-carotene supplementation trial in rural Nepal, geometric mean thymulin concentration was 1.37 ng/ml (95% CI 1.27 to 1.47), positively associated with gestational age at delivery, with maternal beta-carotene supplementation, and with all anthropometric measures, and showing seasonal variation lower during the monsoon and pre-harvest seasons ^5. Reviews discuss the possibility of restoring circulating thymulin in humans as a prospect rather than something tested ^6.

Animal research

In rats on restricted zinc, serum thymulin activity was 61% lower than in zinc-adequate controls, exceeding the differences seen for serum zinc, extracellular superoxide dismutase, 5'-nucleotidase and liver metallothionein ^3. In aged mice, thymulin suppressed pro-inflammatory cytokine production by myeloid cells, improved tumour control and survival and sensitised tumours to anti-PD-L1 treatment in an age-dependent way ^1. Other mouse and rat work reports attenuation of inflammatory pain behaviour with changes in spinal signalling ^7, protection against chronic septic inflammation with free or nanoparticle-bound thymulin ^8, protection in experimental autoimmune encephalomyelitis and blood-brain barrier models ^6, protection in a streptozotocin type 1 diabetes model, and reversal of airway pathology in experimental allergic asthma using nanoparticle-based thymulin gene therapy ^9. Thymulin gene-therapy experiments in congenitally athymic (nude) mice reported prevention of some hormonal and reproductive abnormalities ^6.

In-vitro research

In fetal alveolar type II epithelial cells, thymulin selectively reduced endotoxin-induced IL-1beta release, increased cAMP, and reduced nuclear translocation and DNA-binding activity of NF-kappaB subunits, effects partly amplified by zinc ^4. NMR studies characterised the Zn(II)-nonapeptide complex and its distinct structure ^10, and monoclonal antibody work demonstrated a zinc-dependent epitope, with activity lost in the zinc-free peptide ^2.

Key studies

Dardenne et al., Proc Natl Acad Sci U S A (1985)
Monoclonal antibody characterisation with biological and immunofluorescence assays
Model: Laboratory (antibodies, thymic epithelial cells)
Biological activity was strictly dependent on zinc in the molecule, and two monoclonal antibodies recognised exclusively the zinc-coupled form, indicating a zinc-specific conformation.
Kanemaru et al., Nat Commun (2026)
Heterochronic parabiosis, bone marrow chimeras, integrative analyses and tumour treatment experiments
Model: Animals (aged mice) with human myeloid-cell analyses
Thymulin was identified as a circulating factor declining with age that suppresses myeloid pro-inflammatory cytokine production via NF-kappaB inhibition; it enhanced antitumour T-cell immunity and sensitised tumours to anti-PD-L1 treatment in an age-dependent manner.
DiSilvestro et al., Biol Trace Elem Res (2021)
Comparison of five zinc-status measures in rats fed two levels of dietary zinc
Model: Animals (rats)
Serum thymulin activity was 61% lower on restricted zinc versus adequate zinc, a larger difference than serum zinc (31%), extracellular superoxide dismutase (18%), 5'-nucleotidase (26%) or liver metallothionein (28%).
Haddad, Mol Immunol (2009)
Cell culture with cytokine measurement, cAMP assays and NF-kappaB translocation and DNA-binding assays
Model: Cells (fetal alveolar type II epithelial cells)
Thymulin reduced endotoxin-induced IL-1beta release but not IL-6 or TNF-alpha, raised cAMP, and reduced NF-kappaB nuclear translocation and DNA binding; zinc acted independently and amplified the effect.
Palmer et al., J Dev Orig Health Dis (2020)
Observational follow-up of children born to participants in a cluster-randomised maternal supplementation trial, with thymulin measured as a proxy for thymic size and function
Model: Humans (290 children aged 9 to 13 years, rural Nepal)
Geometric mean thymulin was 1.37 ng/ml; concentrations were positively associated with gestational age at delivery, maternal beta-carotene supplementation and anthropometric measures, with significant seasonal variation.
Reggiani et al., Curr Pharm Des (review) (2014)
Narrative review of thymulin physiology, the thymulin-neuroendocrine axis and gene-therapy tools
Model: Not applicable
Summarises thymulin as a thymic epithelial hormone under neuroendocrine control with reported anti-inflammatory and analgesic properties, and describes adenovector systems expressing the analogue metFTS as experimental tools.

Published adverse-event data

Reported in the cited trials or product labels. Frequencies apply to the stated population and do not transfer to other settings.

Emerging safety signals

No human safety data were identified; no treatment trial in people was located in the sources reviewed ^5,6. ⁶ (2026)
FDA places "Thymulin acetate" in Category 3 of its 503A bulk drug substances list, the category for substances nominated for compounding without adequate support, as updated May 14, 2026 ^12. ¹² (2026)

What is not known: Whether exogenous thymulin does anything in people is untested in the sources reviewed: the human literature is observational biomarker work ^5. Pharmacokinetics and half-life were not located for any species. Because activity requires bound zinc, how much of any reported effect is attributable to the peptide rather than to zinc is a recurring question, and one cell study found zinc active on its own ^3,4. Whether the ageing-related findings in mice extend to humans, how stable the zinc complex is in a research preparation, and whether gene-therapy approaches translate are all open ^1,6,9.

Background viewing

We haven't found a clinician video focused on Thymulin yet. Meanwhile, this widely watched talk covers the science of aging in general. It does not discuss Thymulin.

David Sinclair, PhD (Harvard Medical School) on the biology of aging

The Diary Of A CEO · 6.9M views · 2026

These creators are not affiliated with Amiravo and do not endorse Amiravo or any product linked on this site. Nothing here is medical advice. Video views counted on YouTube as of Oct 24, 2026.

Regulatory status

Status: Not approved for any use. No Drugs@FDA application record was returned on 24 October 2026 ^13, and "Thymulin acetate" appears in Category 3 of FDA's 503A bulk drug substances list, the category for substances nominated for compounding without adequate support, as updated May 14, 2026 ^12. Human work located is observational, using circulating thymulin as a biomarker rather than giving it as a treatment ^5.
United States (FDA): Not approved for any use. An openFDA Drugs@FDA query for thymulin returned no application record on 24 October 2026 ^13. "Thymulin acetate" appears in Category 3 of FDA's 503A bulk drug substances list, substances nominated for use in compounding without adequate support, as updated May 14, 2026 ^12.
Sport (WADA): Not named individually in the sources reviewed; S0 covers substances without governmental approval for human therapeutic use, prohibited at all times ^14.

Status varies by country and changes over time. How we describe regulatory status.

Quality and testing notes

The decisive question for this molecule is zinc. Activity requires zinc bound within the peptide, so a certificate of analysis should state whether material is supplied as the apo-peptide (serum thymic factor, FTS) or as the zinc complex, and should report zinc content if the complex is claimed [2, 10]. Expect identity by mass spectrometry against the expected mass for the nonapeptide (PubChem lists C33H54N12O15, about 859 Da, for the metal-free entry), confirmation of the N-terminal pyroglutamate, purity by reverse-phase HPLC with the trace shown, net peptide content separate from gross weight, counter-ion identity (acetate forms are listed) and an endotoxin measurement [11]. Bioassay-based "thymulin activity" figures are not interchangeable with peptide mass, since the assays respond to the zinc-bound conformation [2, 3].

How purity testing works · Reading a certificate of analysis

Check a Thymulin certificate of analysis against its expected mass (858.9 Da)

Storage and handling

General research-context handling only. Lyophilised peptides of this type are generally kept dry, cool and protected from light and moisture; a metal-peptide complex also raises questions of metal loss or exchange in solution and in the presence of chelators, so aqueous preparations are treated as short-lived. Defer to supplier documentation for the specific lot. No temperatures or preparation steps are given here.

Frequently asked questions

What is thymulin?

It is a nonapeptide hormone produced by thymic epithelial cells, active only when bound to zinc; the zinc-free peptide is called serum thymic factor or FTS ^2,6.

Why does the zinc matter?

Biological activity is strictly dependent on zinc in the molecule, and monoclonal antibodies raised against the zinc-coupled form recognise only that form, consistent with NMR evidence that the zinc complex has a distinct structure ^2,10.

Has thymulin been given to people in a trial?

No treatment trial in people was identified in the sources reviewed. The human work located is observational, measuring circulating thymulin as a biomarker ^5,6.

What is it used for in research?

Mainly as a measure of zinc and thymic status, and as a test compound in animal and cell models of inflammation, pain, autoimmune disease and allergic airway disease ^{1,3,5,6,7,8,9.}

What does the 2026 ageing study report?

In aged mice, thymulin declined with age and suppressed pro-inflammatory cytokine production by myeloid cells through NF-kappaB inhibition, with reported improvements in tumour control and sensitisation to anti-PD-L1 treatment in an age-dependent manner ^1.

Does zinc supplementation raise thymulin?

Thymulin activity falls with restricted zinc in rats and was the most sensitive of five zinc-status measures compared, which is why the assay is treated partly as a zinc-status readout ^3. Whether supplementation in people changes outcomes through thymulin was not addressed in the sources reviewed.

Is thymulin approved or available by prescription?

No. No Drugs@FDA application record was returned, and "Thymulin acetate" sits in Category 3 of FDA's 503A bulk drug substances list, nominated for compounding without adequate support ^12,13.

Is it banned in sport?

It is not named individually in the sources reviewed; S0 covers substances with no current governmental approval for human therapeutic use, prohibited at all times, so athletes should ask their anti-doping organisation ^14.

Latest indexed research

No new studies were filed in the last sweep.

Search all studies on Thymulin (PubMed, Europe PMC, ClinicalTrials.gov)

Listed by publication type from the index record. Inclusion is not an endorsement; open the source to read the findings.

Revision history

Meaningful changes to this entry, with dates and sources. Last reviewed Oct 24, 2026. Typo and layout fixes are not listed.

New section· entryOct 24, 2026
New research reference added: Thymulin.

References

Thymulin restrains age-associated myeloid inflammation and enhances cancer immunotherapy Nat Commun. 2026
A zinc-dependent epitope on the molecule of thymulin, a thymic hormone Proc Natl Acad Sci U S A. 1985
Comparison of Thymulin Activity with Other Measures of Marginal Zinc Deficiency Biol Trace Elem Res. 2021
Thymulin and zinc (Zn2+)-mediated inhibition of endotoxin-induced production of proinflammatory cytokines and NF-kappaB nuclear translocation and activation in the alveolar epithelium Mol Immunol. 2009
Prenatal and childhood exposures are associated with thymulin concentrations in young adolescent children in rural Nepal J Dev Orig Health Dis. 2020
Physiology and therapeutic potential of the thymic peptide thymulin Curr Pharm Des. 2014
Thymulin treatment attenuates inflammatory pain by modulating spinal cellular and molecular signaling pathways Int Immunopharmacol. 2019
Thymulin, free or bound to PBCA nanoparticles, protects mice against chronic septic inflammation PLoS One. 2018
Nanoparticle-based thymulin gene therapy therapeutically reverses key pathology of experimental allergic asthma Sci Adv. 2020
NMR study of a lymphocyte differentiating thymic factor. An investigation of the Zn(II)-nonapeptide complexes (thymulin) J Biol Chem. 1988
Thymulin (CID 71300623) PubChem. 2026
Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act (updated May 14, 2026): "Thymulin acetate" appears in Category 3, substances nominated without adequate support FDA. 2026
Drugs@FDA application data queried through openFDA for thymulin (no matching application record returned on 24 October 2026) openFDA / Drugs@FDA. 2026
International Standard: Prohibited List 2026 World Anti-Doping Agency. 2026

Last reviewed October 24, 2026 by the Amiravo editorial team.

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Specifications

Molecular formula: C₃₃H₅₄N₁₂O₁₅
Molecular weight: 858.9 g/mol
CAS number: 78922-62-0
PubChem CID: 71300623
Sequence: pGlu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn (zinc-bound in the biologically active form)
Type: Single compound

Identifiers from PubChem. Verify against the supplier’s documentation for your lot.

Research stats

How much has been published, not how good it is.

PubMed records: 547
Indexed as human research: 245
Animal-only research: 275
Randomized controlled trials: 5
Registered trials: 0
Trials with posted results: 0
FDA adverse-event reports (FAERS): 1
NIH-funded projects naming it: 26

PubMed records per year (current year is partial).

Counts from title/abstract searches of PubMed, ClinicalTrials.gov, openFDA and NIH RePORTER, checked 2026-10-24. Names shared with other substances can inflate counts. FAERS reports are spontaneous and do not establish cause. Funding shows interest, not evidence. Method

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