Thymosin Alpha-1 (Tα1, thymalfasin) is a 28-residue, N-terminally acetylated peptide originally isolated from thymosin fraction 5 of the thymus gland; it is cleaved from the precursor protein prothymosin-α.1 It is studied as an immune modulator rather than a stimulant, and is reported to act on T-cell maturation and innate immune signalling.2 Outside the United States it is marketed as thymalfasin (Zadaxin) and is approved in 35+ countries for chronic hepatitis B and as a vaccine adjuvant; it has never received FDA approval in the US, where it is handled as a compounded substance.5 All material on this page is provided for research-use-only purposes. The published clinical record is mixed: some randomized trials report benefit while a placebo-controlled phase III hepatitis B study did not confirm efficacy.3 Statements below use “studies reported” framing and reflect findings in the cited models only; they are not directions for use and not medical claims.
Sequence & identity
Chemical identity per PubChem CID 16130571 (InChIKey NZVYCXVTEHPMHE-ZSUJOUNUSA-N); the molecule is acetylated at the N-terminal serine.1
Mechanisms studied
Researchers reported that Tα1 acts largely through pattern-recognition signalling on antigen-presenting cells. In murine and human dendritic cells, Tα1 was observed to drive MyD88-dependent Toll-like receptor signalling that matures dendritic cells and primes Th1 antifungal responses.2 Subsequent work reported that Tα1 enhances TLR2/TLR9-driven NF-κB activation in monocytes and dendritic cells, increasing TNF-α, IL-12 and IFN-α, while simultaneously inducing indoleamine-2,3-dioxygenase (IDO) and a regulatory, tolerogenic environment — a dual action interpreted by the authors as restoring immune balance rather than simple stimulation.2 In clinical samples, researchers observed increases in circulating T-cell counts and reversal of T-cell exhaustion markers (PD-1, Tim-3) alongside restoration of lymphocyte counts.6
Dosing in the research literature
The figures below summarise regimens as reported in published research — they are not recommendations or directions for use.
| Source / model | Regimen reported | Notes |
|---|---|---|
| Phase III chronic hepatitis B RCT (Mutchnick et al., J Viral Hepat 1999) | 1.6 mg subcutaneously twice weekly for 6 months | As reported in studies. In this 97-patient double-blind, placebo-controlled trial a sustained complete response occurred in 14% (Tα1) vs 4% (placebo), a difference that did not reach significance (P=0.084); the authors stated their data did not confirm efficacy seen in other studies.3 Not a direction for use. |
| Dose-ranging chronic hepatitis B RCT (Iino et al., J Viral Hepat 2005; n=316) | 0.8 mg or 1.6 mg subcutaneously twice weekly for 24 weeks | As reported in studies. At the end of the 72-week observation period (12 months after stopping therapy), the 1.6 mg arm reached 36.4% ALT normalization and ~30% HBV-DNA clearance by branched-DNA assay; the 0.8 mg arm showed comparable rates.4 Reported in a hepatitis B patient population only; not a direction for use. |
| Severe sepsis RCT — ETASS (Wu et al., Crit Care 2013) | 1.6 mg subcutaneously twice daily for 5 days, then once daily for 2 days | As reported in studies. 28-day mortality was 26.0% (Tα1) vs 35.0% (control; log-rank P=0.049, non-stratified P=0.062); in-hospital mortality RR 0.73 (95% CI 0.54–0.98, P=0.032).7 Regimen documented in an ICU trial; not a direction for use. |
| Severe COVID-19 retrospective study (Liu et al., Clin Infect Dis 2020) | Reported as subcutaneous administration in hospitalized patients (exact mg/schedule not specified in the report) | As reported in studies. In 76 severe cases, mortality was 11.1% (Tα1) vs 30.0% (no Tα1), P=0.044; this is retrospective, non-randomized data.6 Limited published data on the precise regimen. |
Effects observed in research
In chronic hepatitis B, randomized trials reported variable results: some studies observed increased ALT normalization and HBV-DNA clearance, while a placebo-controlled phase III study did not confirm a significant sustained response.34 In severe sepsis, the ETASS randomized trial reported a lower in-hospital mortality and improved monocyte HLA-DR expression in the Tα1 group, with a borderline 28-day mortality result (significant by log-rank, non-significant by non-stratified analysis).7 In a retrospective COVID-19 cohort, investigators observed lower mortality together with restoration of lymphocyte counts and reversal of T-cell exhaustion markers.6 Across reports the peptide was generally described as well tolerated, with injection-site reactions noted; these are observations within the cited study populations and not statements of clinical benefit for any individual.
Strength of evidence
Grade B — limited human data. The strongest evidence is in chronic hepatitis B, where thymalfasin is an approved drug in 35+ countries (Zadaxin) and has been tested in several randomized trials and a phase III study; however, results are heterogeneous and the pivotal placebo-controlled trial did not reach statistical significance.3 A multicenter randomized trial in severe sepsis (ETASS) reported a favourable but not definitive mortality signal.7 COVID-19 data are retrospective and non-randomized, and later analyses urged caution.6 Mechanistic support (TLR/dendritic-cell activation) is strong in animal and cell models.2 Thymosin Alpha-1 is not FDA-approved in the United States; material sold here is research-use-only and not for human or veterinary use.5
Reconstitution & storage
Reconstitute with bacteriostatic water for laboratory handling. Store lyophilised material frozen and reconstituted material refrigerated. Use Peptigo’s reconstitution calculator and storage cheat sheet for working figures.
References
- PubChem Compound Summary for CID 16130571, Thymosin α1 (thymalfasin). National Library of Medicine. CAS 62304-98-7; C129H215N33O55; MW 3108.3; InChIKey NZVYCXVTEHPMHE-ZSUJOUNUSA-N. https://pubchem.ncbi.nlm.nih.gov/compound/16130571
- Romani L, Bistoni F, Gaziano R, et al. Thymosin α1 activates dendritic cells for antifungal Th1 resistance through Toll-like receptor signaling. Blood. 2004;103(11):4232-4239. https://pubmed.ncbi.nlm.nih.gov/14982877/ — and Romani L, Bistoni F, Montagnoli C, et al. Thymosin α1: an endogenous regulator of inflammation, immunity, and tolerance. Blood. 2006;108(7):2265-2274 (TLR2/TLR9 and IDO/tolerogenic dual action). https://pubmed.ncbi.nlm.nih.gov/16741252/
- Mutchnick MG, Lindsay KL, Schiff ER, et al. Thymosin alpha1 treatment of chronic hepatitis B: results of a phase III multicentre, randomized, double-blind and placebo-controlled study. J Viral Hepat. 1999;6(5):397-403. https://pubmed.ncbi.nlm.nih.gov/10607256/
- Iino S, Toyota J, Kumada H, et al. The efficacy and safety of thymosin alpha-1 in Japanese patients with chronic hepatitis B; results from a randomized clinical trial. J Viral Hepat. 2005;12(3):300-306 (n=316; 0.8 vs 1.6 mg twice weekly for 24 weeks; 36.4% ALT normalization and ~30% HBV-DNA clearance in the 1.6 mg arm at week 72). https://pubmed.ncbi.nlm.nih.gov/15850471/
- Regulatory status: thymalfasin (Zadaxin) approved in 35+ countries for chronic hepatitis B / vaccine adjuvant; not FDA-approved in the United States. SciClone Pharmaceuticals prescribing information / regulatory summaries (Zadaxin).
- Liu Y, Pang Y, Hu Z, et al. Thymosin alpha 1 (Tα1) reduces the mortality of severe COVID-19 by restoration of lymphocytopenia and reversion of exhausted T cells. Clin Infect Dis. 2020;71(16):2150-2157. https://pubmed.ncbi.nlm.nih.gov/32442287/
- Wu J, Zhou L, Liu J, et al. The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial. Crit Care. 2013;17(1):R8. https://pubmed.ncbi.nlm.nih.gov/23327199/