Thymosin Alpha-1 vs TB-500: what the published research shows

At a glance

Same family name, different molecules

The name "thymosin" comes from the thymus, the small organ behind the breastbone where immune T cells mature. In the 1970s, researchers prepared an extract from calf thymus called thymosin fraction 5 and then separated out its individual peptides. Thymosin alpha-1 was isolated from it in 1977, and thymosin beta-4 was separated from the same extract.

That shared origin is where the similarity ends. A 2020 review describes the two as having "vastly different chemical compositions and immunological actions". Thymosin alpha-1 is an immune-signalling peptide. Thymosin beta-4 belongs to a family of proteins that hold on to actin, the building block cells use to move and change shape. Their sequences are unrelated, and thymosin beta-4 is about 60% heavier than thymosin alpha-1.

Thymosin alpha-1 in the research

Thymosin alpha-1 research centres on dendritic cells, the immune system's early-warning cells. Studies from the University of Perugia showed that it acts through Toll-like receptor 9 (TLR9), one of the receptors dendritic cells use to detect infection. Through this route it helped prime anti-fungal T-cell responses, and also switched on a regulatory pathway that helps keep inflammation in check. Researchers describe it as a regulator that helps balance immune activation and tolerance.

It has moved further into the clinic than almost any peptide in this group. Synthetic thymosin alpha-1, thymalfasin, is approved in more than 35 countries for hepatitis B and C, and as an immune enhancer in other conditions. Reviews describe it as well tolerated, with the most common side effect being irritation at the injection site. A 2026 Cochrane review of hepatitis B gathered 10 randomised trials with 1,349 participants, run in Bangladesh, China, Italy, Korea, Singapore and Taiwan.

Its biggest recent test was the TESTS trial, published in the BMJ in 2025. Researchers randomly assigned 1,106 adults with sepsis in 22 Chinese hospitals to thymosin alpha-1 or placebo, in a double-blind design. No safety outcome differed between the groups. Pre-planned subgroup analyses suggested the effect may differ by age and between people with and without diabetes.

TB-500 and thymosin beta-4 in the research

TB-500 is the name used for a short, acetylated fragment of thymosin beta-4. Doping-control laboratories identified the fragment Ac-LKKTETQ, residues 17 to 23 of the full protein, as the active content of products sold as TB-500.

Most of the biological research used full-length thymosin beta-4. In a rat wound model, it increased re-epithelialisation by 42% at day 4 and up to 61% at day 7 compared with saline. In mice, it promoted heart muscle cell migration and survival, a result published in Nature in 2004. In people, a small phase 2 trial of thymosin beta-4 eye drops for severe dry eye reported improvements over the control solution.

Research on the fragment itself is newer. A 2024 study tracked how TB-500 breaks down in the lab and in rats, and found that one of its metabolites, Ac-LKKTE, showed significant wound-healing activity in a cell assay.

Where the research stands

Thymosin alpha-1 has far more human data than most research peptides, but the results are still being worked out. In the TESTS sepsis trial, 28-day mortality was 23.4% with thymosin alpha-1 and 24.1% with placebo, a difference that was not significant. The 2026 Cochrane review rated most of the hepatitis B evidence as very low certainty, so its effects there remain uncertain. Thymosin alpha-1 is not an approved medicine in Australia.

For TB-500, the main gap is that there are no published human trials of the fragment, and most findings come from full-length thymosin beta-4. TB-500 is a research compound with no approval anywhere.

The two also differ in sport. WADA prohibits thymosin beta-4 and its derivatives, including TB-500, at all times under S2. Thymosin alpha-1 is not named on the Prohibited List, and because it is approved in several countries, WADA's S0 catch-all for unapproved substances is unlikely to apply. That is a reading of the list, not an official ruling, so anyone subject to testing should check with their anti-doping organisation.

Sources

• Dominari et al., World J Virol (2020) — Thymosin alpha 1: a comprehensive review of the literature
• Romani et al., Blood (2006) — Thymosin alpha1 activates dendritic cell tryptophan catabolism and balances inflammation and tolerance
• Romani et al., Ann N Y Acad Sci (2007) — Thymosin alpha1: an endogenous regulator of inflammation, immunity and tolerance
• Garaci et al., Ann N Y Acad Sci (2007) — Thymosin alpha1: a historical overview
• Naing et al., Cochrane Database Syst Rev (2026) — Thymosin-α1 for people with chronic hepatitis B
• Wu et al., BMJ (2025) — The efficacy and safety of thymosin α1 for sepsis (TESTS): phase 3 trial
• Malinda et al., J Invest Dermatol (1999) — Thymosin beta-4 accelerates wound healing
• Bock-Marquette et al., Nature (2004) — Thymosin beta-4, integrin-linked kinase and cardiac repair
• Sosne et al., Cornea (2015) — Thymosin beta-4 eye drops in a phase 2 dry eye trial
• Esposito et al., Drug Test Anal (2012) — Ac-LKKTETQ identified in TB-500
• Rahaman et al., J Chromatogr B (2024) — TB-500 metabolites in vitro and in rats
• WADA — The Prohibited List
• PubChem — Thymalfasin (CID 16130571)
• PubChem — TB-500 fragment (CID 62707662)