Thymosin Alpha-1
Human RCTThymosin α1 · Tα1 · Thymalfasin · Zadaxin · TA1
Highest available evidence among curated papers: Human RCT (as of 2026-06-04).
Chemical & identity
- Sequence
- SDAAVDTSSEITTKDLKEKKEVVEEAEN
- Length
- 28 residues
- Molecular formula
- C129H215N33O55
- Molecular weight
- 3108.3 g/mol · PubChem
- PubChem CID
- 16130571 · PubChem
- SMILES
- CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)C
- InChIKey
- NZVYCXVTEHPMHE-ZSUJOUNUSA-N
- ChEMBL ID
- CHEMBL2103979 · ChEMBL
- UniProt
- P06454 · UniProt
- Category
- Immune
Chemical/structural fields are auto-pulled and source-linked. ChEMBL data: ChEMBL_36, CC BY-SA 3.0.
Mechanism (curated)
Immunomodulatory peptide (N-acetylated 28-residue fragment of prothymosin α); promotes T-cell maturation and function and modulates innate/adaptive immunity (including dendritic-cell and TLR signaling) to help restore immune homeostasis.
Pharmacology & handling
- Half-life
- Approximately 2 hours; administered subcutaneously.
Research
Thymosin α1 and Its Role in Viral Infectious Diseases: The Mechanism and Clinical Application.
Human trialTao N et al. · Molecules (Basel, Switzerland) · 2023 · Narrative review
Thymosin α1 (Tα1) is an immunostimulatory peptide used clinically in viral infectious diseases including hepatitis B, hepatitis C, and AIDS. The abstract describes that Tα1 influences immune cell functions by interacting with Toll-like receptors (TLR2, TLR3, TLR4, TLR7, TLR9) and activating downstream signaling pathways (IRF3, NF-κB, p38MAPK, MyD88) to promote immune cell proliferation and cytokine production. This is a narrative review summarizing the characteristics of Tα1, its immunomodulatory mechanisms, and its clinical applications in antiviral therapy, though the authors note a lack of systematic analysis of its exact clinical efficacy.
Gu B et al. · Frontiers in cellular and infection microbiology · 2025 · Meta-analysis
A systematic review and meta-analysis of 11 randomized controlled trials (967 patients receiving thymosin-α1 versus 960 controls) examined thymosin-α1's effect on 28-day mortality in sepsis. The comprehensive analysis showed a statistically significant reduction in 28-day mortality with thymosin-α1 (OR 0.73, 95% CI: 0.59–0.90, P = 0.003); however, subgroup analyses of high-quality and multi-center trials did not confirm a mortality benefit. Trial sequential analysis indicated the current sample size is inadequate, and heterogeneity of treatment effects suggested potential benefits may be restricted to specific subgroups (cancer, diabetes, coronary heart disease) with variable credibility. The authors conclude that thymosin-α1 has potential to reduce 28-day mortality in sepsis but efficacy varies by subgroup, emphasizing the need for personalized immunotherapy strategies in future trials.
Wang S et al. · Journal for immunotherapy of cancer · 2023 · Other
This study evaluated the combination of zoledronic acid (ZA) and thymosin α1 (Tα1) for treating advanced or metastatic prostate cancer. A retrospective clinical analysis found that androgen deprivation therapy combined with ZA plus Tα1 improved therapeutic outcomes in patients with prostate cancer and was associated with enhanced T cell frequency. In a mouse prostate cancer allograft model, ZA and Tα1 synergistically inhibited tumor growth, increased infiltration of cytotoxic CD8+ T cells, and enhanced tumor inflammation. The treatment relieved immunosuppression in cancer cells, stimulated pro-inflammatory macrophages, and enhanced T cell cytotoxic function by blocking the MyD88/NF-κB pathway in cancer cells while activating it in macrophages and T cells.
Shehadeh F et al. · The Journal of infectious diseases · 2023 · RCT
A prospective, open-label, randomized trial of 49 hospitalized COVID-19 patients with hypoxemia and lymphocytopenia compared thymalfasin (synthetic thymosin-α-1) to standard of care. Clinical recovery was numerically higher in treated patients across both low-flow and high-flow oxygen groups, but differences were not statistically significant. Among low-flow oxygen patients, thymosin-α-1 treatment resulted in a significantly greater increase in CD4+ T cells on day 5 versus day 1 compared to controls (3.84-fold difference, P=0.01). Nine serious adverse events in treated patients were deemed unrelated to thymosin-α-1.
Aynekulu Mersha DG et al. · Brain, behavior, & immunity - health · 2025 · Case report/series
This open-label proof-of-concept study treated 5 depressed common variable immunodeficiency (CVID) patients with thymosin alpha-1 (Tα1) at 1.6 mg daily for 1 week then twice weekly for 7 weeks, hypothesizing that increasing naïve T cells would improve mood. All 5 CVID patients showed decreased depression scores (average 52% reduction on Hamilton Depression Rating Scale) and increased naïve/memory CD4+ and CD8+ T cell ratios, with IL-6 reductions in 4 of 5 patients; these changes were not observed in a contrast group of 42 major depressive disorder patients receiving treatment as usual (36% score reduction). Depression recurred in 2 patients during the 8-week washout period, and immune effects were not sustained. The authors conclude the results suggest antidepressive and immune-correcting effects of thymosin alpha-1 and call for larger placebo-controlled trials.
Chen JF et al. · Hepatology international · 2022 · RCT
This open-label randomized controlled trial enrolled 120 patients with hepatitis B virus-related acute-on-chronic liver failure, comparing standard medical therapy alone (N=58) with standard therapy plus thymosin α1 (Tα1) subcutaneously injected at 1.6 mg daily for one week then twice weekly for 11 weeks (N=56). The 90-day cumulated liver transplantation-free survival rate was 75.0% in the Tα1 group versus 53.4% in the control group (p=0.030). The Tα1 group showed significantly lower rates of new infection (32.1% vs 58.6%, p=0.005) and hepatic encephalopathy (8.9% vs 24.1%, p=0.029), with lower mortality from severe infection (8.9% vs 24.1%, p=0.029). The authors conclude that Tα1 is safe and significantly improves 90-day liver transplantation-free survival, possibly through infection prevention.
Tuthill CW et al. · International immunopharmacology · 2023 · RCT
A pilot randomized controlled trial in hemodialysis patients with end-stage renal disease compared thymalfasin (thymosin alpha 1, Ta1) at 1.6 mg subcutaneously twice weekly for 8 weeks versus control to assess whether Ta1 would reduce COVID-19 infection rate, severity, and related hospitalizations. As of the interim report (July 2022), 194 patients were randomized across five dialysis centers in Kansas City, Missouri, with 3 deaths in the Ta1 group versus 7 in controls, and 12 COVID-19-related serious adverse events reported (5 in Ta1 group, 7 in controls). Most patients received COVID-19 vaccine at various times during the study, and antibody responses and final safety/efficacy endpoints are pending completion of the full study.
Li ZH et al. · Immunopharmacology and immunotoxicology · 2026 · RCT
This open-label randomized controlled trial (NCT03082885) examined how thymosin α1 (Tα1) improves outcomes in 73 patients with hepatitis B virus-related acute-on-chronic liver failure (ACLF). Patients received either standard medical therapy alone (n=38) or standard therapy plus Tα1 (n=35). Tα1 treatment significantly increased 90-day transplant-free survival and was associated with reduced frequencies of regulatory T cells (Tregs) and specific Treg subsets at weeks 4-8, while also moderating late-stage hyperinflammatory responses. Survivors at baseline had higher effector T cell proportions, lower Tregs, and higher pro-inflammatory cytokines compared to non-survivors. The authors conclude that Tα1 improves outcomes by rebalancing immune response through T-cell differentiation and cytokine modulation.
Zhang HT et al. · Translational lung cancer research · 2025 · Cohort
This retrospective study of 196 patients with unresectable locally advanced non-small cell lung cancer compared outcomes in patients receiving concurrent chemoradiotherapy (CCRT) with or without thymosin-alpha-1 (Tα1) at two dose schedules (short-term: weekly until end of CCRT; long-term: weekly for 12 months post-CCRT), followed by consolidative nivolumab in eligible patients. The long-term Tα1 group showed improved progression-free survival (not reached vs. 14.6 months in non-Tα1 group, P=0.03), improved overall survival (not reached vs. 20.0 months, P=0.01), reduced grade ≥2 pneumonitis (14.5% vs. 35.4%, P=0.02), and lower lymphopenia at 6 months post-CCRT (22.5% vs. 55.8%, P=0.01). IL-6 levels at 2 months post-CCRT were significantly lower in the long-term Tα1 group (4.92 vs. 8.14 pg/mL, P=0.03). The authors conclude that Tα1 integration may enhance survival and reduce treatment-related toxicity, though they note that further randomized trials are needed for validation.
Soeroto AY et al. · Inflammopharmacology · 2023 · Meta-analysis
This meta-analysis pooled data from 8 studies (published through March 2023) examining thymosin alpha-1 therapy in moderate to critical COVID-19 patients. Pooled results showed that thymosin alpha-1 was associated with significantly lower mortality (RR 0.59, 95% CI 0.37–0.93, p=0.02) compared to control, but did not differ in need for mechanical ventilation or hospital length of stay. The authors conclude thymosin alpha-1 may reduce mortality in moderate to critical COVID-19 and call for additional randomized controlled trials to verify findings.
Linye H et al. · Medicine · 2021 · Cohort
This propensity score matching analysis of 468 patients with solitary hepatitis B virus-related hepatocellular carcinoma who underwent curative resection compared thymosin alpha-1 (Tα1) adjuvant therapy versus control. Patients receiving Tα1 showed improved immunological response, better recurrence-free survival (RFS) and overall survival (OS) both before and after propensity matching, with median follow-up of 60 months. Multivariate analysis identified Tα1 as an independent prognostic factor for both OS (HR=0.308) and RFS (HR=0.381). Virologic response was similar between groups after 24 months.
A multipronged Tα1 reset of CD8<sup>+</sup> T cell cytotoxicity against breast cancer.
In-vitroMishra S et al. · Human immunology · 2026 · In-vitro study
Thymosin α1 (Tα1) is an endogenous thymic peptide that enhanced CD8+ T cell-mediated cytotoxicity against breast cancer cells in vitro. In this study, CD8+ T cells from ten healthy donors were cultured under various conditions and tested against MDA-MB-231 breast cancer cells and CD44+ cancer stem-like cells. Tα1 significantly increased apoptosis, suppressed tumor cell proliferation, increased granzyme B secretion beyond CD3/CD28 stimulation alone, and partially restored effector function in exhausted T cells by reducing PD-1, TIM-3, and LAG-3 expression. Transcriptomic analysis using TCGA-BRCA data (n=1,112) correlated a four-gene Tα1 Response Index with antigen presentation and cytotoxic programs. The authors conclude that Tα1 enhances CD8+ T cell cytotoxicity while alleviating exhaustion, suggesting potential as an immunomodulator for breast cancer.
Liu H et al. · Future cardiology · 2025 · RCT
The PANDA II trial is a multicenter randomized controlled trial evaluating thymosin alpha 1 (Tα1) supplementation in over 330 patients undergoing acute type A aortic dissection repair. Patients are assigned equally to receive Tα1 plus standard care or placebo with standard management. The primary endpoint is the difference in mean postoperative Sequential Organ Failure Assessment (SOFA) scores between groups, measured daily from postoperative day 7. The study aims to establish Tα1 as a therapeutic approach for reducing organ dysfunction mediated by systemic inflammatory response syndrome and improving long-term outcomes in this high-risk population.
Xu H et al. · BMC medicine · 2026 · Other
A phase II prospective clinical trial enrolled 30 patients with locally advanced gastric and gastroesophageal junction adenocarcinoma to evaluate neoadjuvant treatment combining anti-PD-1 (serplulimab) plus chemotherapy (SOX: S-1 and oxaliplatin) with thymalfasin, an immunomodulatory peptide. Pathological complete response was achieved in 30% of patients, major pathological response in 56.7%, and nodal downstaging in 80%. Any-grade adverse events occurred in 93.3% of patients with grade ≥3 in 26.7%; flow cytometry showed CD8+ T cell expansion with increased CD69 expression and reduced HLA-DR+ T cells. RNA sequencing revealed thymalfasin-associated upregulation of genes involved in antigen processing, presentation, and type I interferon signaling, consistent with coordinated systemic antitumor immunity. The authors conclude the combination produced encouraging pathological response with acceptable safety and recommend larger randomized trials.
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Regulatory status
- FDA approved
- No
- WADA prohibited
- No
- Compounding status
- Not FDA-approved in the US; approved/marketed in numerous other countries as thymalfasin (Zadaxin).
- Notes
- Not FDA-approved in the US. Approved/marketed in numerous other countries (thymalfasin / Zadaxin) for chronic hepatitis B and as an immune adjuvant, as of 2026-06-04. Not listed on the WADA prohibited list.
Legal/regulatory status varies by jurisdiction and changes over time — accurate as of last review (2026-06-04).
Data sources: Curated IDs (PubChem/UniProt/ChEMBL) + Europe PMC + ClinicalTrials.gov (2026-06-04).
Last reviewed 2026-06-04