Thymosin alpha-1

What it is

Thymosin alpha-1 (Tα1) is a heat-stable, highly acidic 28-amino-acid peptide first isolated from thymosin fraction 5, a calf thymus extract; Goldstein et al. (1977) reported its sequence and described it as one of several thymic polypeptides that may help regulate T cell function. A chemically synthesized version identical in sequence, thymalfasin, is marketed by SciClone Pharmaceuticals as Zadaxin. Unlike most peptides in this library, it has been tested in randomized human trials with several hundred to more than a thousand participants.

Mechanism of action

Tα1 is described as an immune modulator rather than a direct antiviral or anticancer agent, and the best-characterized pathway runs through innate immune sensing. Romani et al. (2004) reported that Tα1 matured dendritic cells exposed to the mold Aspergillus fumigatus and raised their interleukin-12 output through the p38 MAPK and NF-κB pathways, an effect that depended on Toll-like receptor signaling through the adaptor protein MyD88. In mice the peptide supported T helper 1 antifungal immunity and was associated with protection against aspergillosis in transplant models. In sepsis research, investigators have tracked monocyte HLA-DR expression as a marker of immune suppression, and Wu et al. (2013) reported greater improvement in that marker with Tα1 on days 3 and 7. How these laboratory and biomarker effects relate to clinical outcomes remains uncertain, as the larger trials below show.

What it’s most studied for

Clinical research on Tα1 has concentrated on settings where immune responses are thought to be impaired. The longest-running line is chronic hepatitis B, where randomized trials since the 1990s have measured viral clearance, and a 2026 Cochrane review pooled 10 trials with 1,349 adults. A second line is sepsis, based on the idea that sepsis-related immune suppression worsens outcomes; Chinese investigators ran a 361-patient trial and then a 1,106-patient placebo-controlled phase 3 trial. A third is cancer, where Tα1 has been added to chemotherapy, including a 488-patient randomized trial in metastatic melanoma. The drug is widely used in China and some other countries outside the US.

Notable findings

Each finding carries the species or population it was observed in and the dose that study used. Doses are reported as research context, exactly as published. They are not guidance.

Study quality

Thymosin alpha-1 has a larger human evidence base than most peptides in this library, including randomized trials with several hundred to more than a thousand participants, and its manufacturer has described it as approved in more than 30 countries, though not in the US. The results are mixed. The largest and best-blinded trial, TESTS (n=1,106), found no difference in 28-day sepsis mortality, after a smaller single-blind trial had reported a marginal benefit; both sepsis trials were conducted in China. The 488-patient melanoma trial showed survival trends that did not reach statistical significance. In chronic hepatitis B, a 2026 Cochrane review of 10 trials found Tα1 may reduce all-cause deaths and serious adverse events but called for larger, more rigorous trials. Reported safety has been favorable: TESTS found no significant difference in safety outcomes, and ETASS and Chien et al. recorded no serious drug-related or significant side effects. Mechanistic evidence comes largely from cell and mouse studies.

On the research desk

Recent records on Thymosin alpha-1 from the Alpha Helix research feed, each with its evidence tier and citation.

• Thymosin alpha-1 in cancer therapy: immunomodulatory mechanisms, clinical applications and translational perspectives2026-06-10 · 42641753

References

1. 1
   Goldstein AL, Low TL, McAdoo M, et al. (1977). Thymosin alpha1: isolation and sequence analysis of an immunologically active thymic polypeptide. Proceedings of the National Academy of Sciences of the USA. PMID 265536
2. 2
   Romani L, Bistoni F, Gaziano R, et al. (2004). Thymosin alpha 1 activates dendritic cells for antifungal Th1 resistance through toll-like receptor signaling. Blood. DOI 10.1182/blood-2003-11-4036
3. 3
   Wu J, Pei F, et al. (2025). The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial. BMJ. PMID 39814420
4. 4
   Wu J, Zhou L, Liu J, et al. (2013). The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial. Critical Care. PMID 23327199
5. 5
   Maio M, Mackiewicz A, Testori A, et al. (2010). Large randomized study of thymosin alpha 1, interferon alfa, or both in combination with dacarbazine in patients with metastatic melanoma. Journal of Clinical Oncology. PMID 20194853
6. 6
   Chien RN, Liaw YF, Chen TC, et al. (1998). Efficacy of thymosin alpha1 in patients with chronic hepatitis B: a randomized, controlled trial. Hepatology.
7. 7
   Naing C, Ni H, Aung HH, et al. (2026). Thymosin-α1 for people with chronic hepatitis B. Cochrane Database of Systematic Reviews. DOI 10.1002/14651858.CD014610.pub2
8. 8
   US Food and Drug Administration, Pharmacy Compounding Advisory Committee (2024). FDA briefing document: thymosin alpha-1 related bulk drug substances, Pharmacy Compounding Advisory Committee meeting, December 4, 2024. U.S. Food and Drug Administration.