Thymosin Alpha-1 Research, Specifications & Scientific Information

Introduction

Thymosin alpha-1 is the only compound in this batch that is an approved medicine anywhere. Under the International Nonproprietary Name thymalfasin, and principally under the brand ZADAXIN, it has been registered in a number of countries for chronic hepatitis B and C and as an immune stimulant and adjuvant — a 2009 review by the peptide's discoverer recorded approval in over 35 of them ^[4]. It is not approved in the United States, and the difference between those two statements is the sort of distinction this page exists to keep straight.

It is also, unusually for this library, a compound with a large and formally assessed clinical record — and that record is more equivocal than its approval history suggests. A phase 3 trial in 1106 adults with sepsis found no effect on 28-day mortality ^[9]. A 2026 Cochrane review of its use in chronic hepatitis B rated the certainty of evidence low to very low across every outcome ^[11]. This page sets out the chemistry, the mechanism, and that clinical record as reported, with every source resolved against PubMed, Crossref or ClinicalTrials.gov when the page was built. It describes research, not use.

What Is Thymosin Alpha-1?

Thymosin alpha-1 is a 28-residue, N-terminally acetylated peptide corresponding to the N-terminal portion of prothymosin α. The synthetic material is chemically identical to the naturally occurring peptide; it is not an analogue.

Before anything else, a naming problem has to be cleared. "Thymosin" is not a structural family. The term was applied in the 1960s and 1970s to fractions of calf thymus, and the peptides that came out of those fractions were named by where they ran on a gel, not by what they were. Thymosin alpha-1 and thymosin β4 therefore share a word and nothing else: different precursor proteins, different lengths, different sequences, different binding partners, different pharmacology. Nothing established about one transfers to the other, and the two are regularly conflated in secondary writing.

The compound's regulatory position is genuinely unusual for this library and needs stating precisely:

• Outside the United States, thymalfasin is an approved pharmaceutical product in a number of countries, for indications including chronic hepatitis B and C and use as a vaccine adjuvant and immune stimulant ^[4].
• In the United States, it has not been approved by the U.S. Food and Drug Administration for any indication. It has held orphan drug designation, which supports development and is not an approval.
• Approval is specific to a product, an indication and a jurisdiction. An approval in one country says nothing about the status of a differently manufactured material supplied for laboratory use anywhere.

Public registers carry it under CAS 62304-98-7, PubChem CID 16130571 and UNII W0B22ISQ1C.

Thymosin Alpha-1 Specifications

Thymosin alpha-1 is a 28-residue peptide corresponding to the N-terminal portion of prothymosin alpha, and the synthetic material is chemically identical to the naturally occurring peptide. The sequence above is written in single-letter code and does not show the N-terminal acetyl group, which is present on the molecule: PubChem CID 16130571 and the FDA/NCATS Global Substance Registration System entry under UNII W0B22ISQ1C both describe the N-acetylated peptide, with CAS registry number 62304-98-7, molecular formula C129H215N33O55 and average mass 3108.3 g/mol — the same mass carried in the supplier catalog. The International Nonproprietary Name is thymalfasin, and the principal marketed brand is ZADAXIN. One naming point causes persistent confusion and should be settled at the outset: 'thymosin' was a label applied to fractions of calf thymus in the 1960s and 1970s, not a structural family. Thymosin alpha-1 and thymosin beta-4 share nothing but that historical label — different precursor proteins, different sequences, different lengths, different binding partners, different pharmacology. Nothing established about one transfers to the other. The peptide is highly acidic, with eleven acidic residues against five basic ones, which is why it is soluble and why it behaves very differently from the cationic host-defence peptides elsewhere in this library.

Values that a public register does not carry are shown as not publicly characterised rather than estimated. Identifiers are reference values; the certificate of analysis supplied with a laboratory order is the record for a given lot.

How Does Thymosin Alpha-1 Work?

Not through a receptor of its own, as far as the published work establishes. There is no characterised high-affinity ligand-receptor pair for this peptide, no published dissociation constant at a named target, and no agonist or antagonist classification — which is why those rows in the specification table are qualified rather than filled with a number.

What the literature describes instead is an effect on the behaviour of immune cells, principally dendritic cells, with the signalling traced to Toll-like receptor pathways. Dendritic cells sit at the junction between innate and adaptive immunity: what they do after encountering an antigen determines which kind of T-cell response follows. A molecule that changes their maturation state and their cytokine output is therefore an immunomodulator in a fairly literal sense — it changes the direction of a response rather than switching a pathway on or off.

Two features of that account matter for reading the clinical record. First, an effect mediated through the state of the immune system should be expected to depend on the state the immune system is in, which is the usual explanation offered for why trials in different populations have given different answers. Second, an immunomodulator has no single pharmacodynamic readout, so trials of it tend to use clinical endpoints directly — mortality, tumour response — with immune measures such as monocyte HLA-DR as secondary markers ^[6].

Thymosin Alpha-1 Mechanism of Action

In vitro research

Dendritic cell maturation and Th1 polarisation. In dendritic cells pulsed with Aspergillus fumigatus, thymosin alpha-1 induced functional maturation and interleukin-12 production through a p38 mitogen-activated protein kinase / NF-κB-dependent pathway. The signalling ran through the myeloid differentiation factor 88 (MyD88)-dependent pathway, involving distinct Toll-like receptors ^[1].

Tryptophan catabolism and the tolerance side. A companion study reported that the peptide activates dendritic cell tryptophan catabolism — the indoleamine 2,3-dioxygenase pathway — and the authors framed the result as establishing a regulatory environment balancing inflammation against tolerance ^[2].

Those two papers together are the reason this compound is described as a modulator rather than a stimulant. One reports a pro-inflammatory, Th1-polarising effect; the other reports engagement of a canonically tolerogenic pathway. A molecule that does both is not well described by "boosts the immune system", and the clinical results are easier to read with that in mind.

Analytical characterisation. Liquid chromatography with high-resolution mass spectrometry has been used to identify and quantify structurally related peptide impurities in thymalfasin — deletion, insertion and modification products arising from synthesis ^[8]. For a 28-residue peptide made by solid-phase synthesis, the relevant impurities are sequence-related and close in mass to the target, which is why an impurity profile from an orthogonal method carries information that a single purity percentage does not.

These are observations in cultured cells and in analytical systems. They establish nothing about animals or people on their own.

What Is Thymosin Alpha-1 Being Researched For?

Registered and published research clusters into four areas:

• Chronic viral hepatitis. The indication behind most of the approvals, with randomised trials running from 1991 to 2018 and several meta-analyses ^{[3, 7, 11]}.
• Sepsis and critical care. A 361-patient trial in severe sepsis ^{[6, 12]} followed by a 1106-patient phase 3 ^{[9, 14]}, plus a phase 4 trial in acute necrotising pancreatitis ^[13].
• Oncology adjunct. A 488-patient randomised study in metastatic melanoma ^[5], and an ongoing phase 3 adjuvant trial with a planned enrolment of 2500 after resection of stage II and III colorectal cancer ^[15].
• Infection and transplantation immunology. The antifungal and dendritic-cell work described above ^{[1, 2]}.

Human Research on Thymosin Alpha-1

Human clinical research

Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.

Phase 3 in sepsis (TESTS)

Population. 1106 adults aged 18 to 85 with sepsis by Sepsis-3 criteria, at 22 centres in China between September 2016 and December 2020, randomised 1:1 and stratified by age and centre. 1089 entered the modified intention-to-treat analysis: 542 in the thymosin α1 group and 547 on placebo ^{[9, 14]}.

Endpoint and design. Multicentre, double-blinded, placebo-controlled. The primary outcome was 28-day all-cause mortality after randomisation. Subcutaneous administration every 12 hours for seven days, unless stopped for discharge from intensive care, death or withdrawal of consent ^[9].

Result. The primary outcome was null. 28-day all-cause mortality occurred in 127 participants (23.4%) in the thymosin α1 group and 132 (24.1%) on placebo — hazard ratio 0.99, 95% CI 0.77 to 1.27, p = 0.93 by log-rank test. No secondary or safety outcome differed statistically significantly. Prespecified subgroup analysis showed a potential differential effect by age (under 60 years: hazard ratio 1.67, 1.04 to 2.67; 60 and over: 0.81, 0.61 to 1.09; p for interaction = 0.01) and by diabetes (diabetes: 0.58, 0.35 to 0.99; no diabetes: 1.16, 0.87 to 1.53; p for interaction = 0.04). The authors concluded that the trial found no clear evidence that thymosin α1 decreases 28-day all-cause mortality in adults with sepsis ^[9].

Limitations. Conducted entirely in China, which bounds generalisation. The subgroup interactions are the kind of finding that generates hypotheses rather than conclusions, and the direction in the younger subgroup — a point estimate above 1 — is a reason for caution rather than encouragement. Several authors received grants from the product's manufacturer, declared in the paper.

Earlier trial in severe sepsis (ETASS)

Population. 361 patients with severe sepsis in six tertiary teaching hospitals in China between May 2008 and December 2010, randomised 1:1 to control (n = 180) or thymosin α1 (n = 181) ^{[6, 12]}.

Endpoint and design. Multicentre, single-blind, randomised controlled. Primary outcome death from any cause at 28 days; secondary outcomes the dynamics of Sequential Organ Failure Assessment score and monocyte HLA-DR at days 0, 3 and 7 ^[6].

Result. 28-day mortality was 26.0% with thymosin α1 and 35.0% in the control group, with a marginal p value (non-stratified p = 0.062; log rank p = 0.049) and a relative risk of 0.74 (95% CI 0.54 to 1.02). Greater improvement in monocyte HLA-DR was seen at day 3 (mean difference 3.9%, 95% CI 0.2 to 7.6, p = 0.037) and day 7 (5.8%, 1.0 to 10.5, p = 0.017). No serious drug-related adverse event was recorded ^[6].

Limitations. Single-blind, with a confidence interval for the primary outcome that crosses 1 and a p value that depends on which test is applied. Read together with TESTS, this is the familiar sequence of a promising smaller trial that a larger, better-blinded one did not confirm — and the larger trial is the more informative of the two.

Meta-analysis of the sepsis literature

A 2025 systematic review and meta-analysis included 11 randomised trials with 967 patients in thymosin α1 groups and 960 controls. The pooled estimate showed a reduction in 28-day mortality (odds ratio 0.73, 95% CI 0.59 to 0.90, p = 0.003), but the high-quality subgroup (0.82, 0.65 to 1.03, p = 0.09) and the multicentre subgroup (0.86, 0.68 to 1.08, p = 0.20) showed no mortality benefit. Trial sequential analysis indicated that the accumulated sample size is inadequate ^[10].

Limitations. A pooled benefit that disappears in the higher-quality subset is a classic signature of small-study effects. The authors' own framing is that efficacy differs between subgroups and that personalised approaches are needed — which is a statement about uncertainty, not about effect.

Chronic hepatitis B

The formal assessment. A 2026 Cochrane review searched to 10 June 2026 and included 10 randomised trials with 1349 participants, conducted in Bangladesh, China, Italy, Korea, Singapore and Taiwan and published between 1991 and 2018. Comparators were placebo, no intervention, or the same co-intervention; follow-up ranged from six months to five years (median 12 months). Pooled results suggested thymosin-α1 may reduce all-cause mortality (RR 0.53, 95% CI 0.29 to 0.96; 3 studies, 907 participants), serious adverse events (RR 0.72, 0.53 to 0.99; 5 studies, 1056 participants), HBV-related mortality (RR 0.53, 0.29 to 0.96) and non-serious adverse events (RR 0.47, 0.27 to 0.83), with little or no effect on quality of life or histological improvement ^[11].

The certainty attached to those numbers. Low for serious adverse events and very low for every other outcome, downgraded for risk of bias, imprecision and heterogeneity. The authors' conclusion is explicit: they are not sure whether thymosin-α1 reduces any of those outcomes. Sixteen further studies are awaiting assessment because of incomplete reporting ^[11].

Earlier meta-analyses reached more favourable conclusions on comparisons against interferon alpha ^[3] and on combination with entecavir in HBV-related cirrhosis ^[7]. The Cochrane review is the most recent and the most methodologically conservative of the three, and where they disagree this page follows it.

Metastatic melanoma

Population. 488 patients with metastatic melanoma, randomised across five treatment groups combining dacarbazine, interferon alfa and thymosin α1 at 1.6, 3.2 or 6.4 mg ^[5].

Result. Median overall survival was 9.4 months in patients given thymosin α1 against 6.6 months in the control group (hazard ratio 0.80, 95% CI 0.63 to 1.02, p = 0.08), with a similar pattern for progression-free survival (hazard ratio 0.80, 0.63 to 1.01, p = 0.06). Adding the peptide did not produce additional toxicity. The authors concluded that the results suggest activity and provide a rationale for further evaluation ^[5].

Limitations. Both primary survival comparisons fell short of conventional significance. A trial whose headline hazard ratios have confidence intervals crossing 1 supports further study, which is what its authors said, and does not support a claim of effect.

Preclinical Research on Thymosin Alpha-1

Animal research

The animal work most often cited is the in vivo half of the dendritic cell study. In mice receiving haematopoietic transplants and highly susceptible to aspergillosis, the synthetic peptide activated T-helper 1-dependent antifungal immunity, accelerated myeloid cell reconstitution, and protected the animals from infection ^[1].

The design of that experiment is what gives it weight: the mechanism was worked out in dendritic cells, the prediction was that Th1 polarisation would protect a specifically immunocompromised host, and the in vivo result matched the prediction in exactly that host. It is a much tighter argument than a broad survey of models would be.

It is also narrow. The animal literature for this compound is small relative to its clinical literature — the reverse of the usual pattern in this library, and a consequence of the compound having entered human use decades ago. Findings described in this section were observed in animals, and nothing in them establishes anything about humans.

Other Areas of Thymosin Alpha-1 Research

Human clinical research

Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.

Critical care beyond sepsis. A phase 4 trial with 508 participants examined thymosin alpha-1 in the prevention of pancreatic infection after acute necrotising pancreatitis ^[13]. The design reflects the same reasoning as the sepsis programme: infection after a severe inflammatory insult is a problem of immune competence as much as of microbiology.

Oncology adjunct, ongoing. A phase 3 trial with a planned enrolment of 2500 is recruiting, testing thymosin-alpha 1 as adjuvant treatment after radical resection of high-risk stage II and III colorectal cancer ^[15]. It has no results. A trial of that size in an adjuvant setting is the kind of study that would settle a question the earlier melanoma work left open, and it has not reported.

The pattern across indications. Read together, the completed trials share a shape: plausible mechanism, encouraging early or mid-size studies, and larger or more rigorously assessed evidence that does not confirm them. TESTS did not confirm ETASS ^{[9, 6]}. The high-quality subgroup of the sepsis meta-analysis did not confirm the pooled estimate ^[10]. The Cochrane assessment rated the hepatitis B evidence very low despite three decades of trials ^[11]. None of that makes the compound inactive; it means the size of any effect is not established, and that an approval history is not the same thing as a settled evidence base.

Current Research Status

Status as of September 22, 2026. This block is rendered from maintained fields, not from prose, so it cannot go stale in one place and stay current in another.

Thymosin Alpha-1 vs Related Compounds

Composition and mechanism only; no comparison of effect is made between these compounds.

The thymosin name

Thymosin alpha-1 — 28 residues, from prothymosin α, acting on immune cells. Thymosin β4 — 43 residues, from the β-thymosin family, binding monomeric actin. The two were named after the calf thymus fractions they were purified from and are otherwise unrelated. Thymalin and thymulin are further distinct substances from the same historical programme.

Charge and character

Thymosin alpha-1 is strongly acidic — eleven acidic residues against five basic ones. LL-37 is strongly cationic, and that difference is the whole of the difference between an immunomodulatory peptide and a membrane-active one.

Mechanism

Thymosin alpha-1 — Toll-like receptor signalling in dendritic cells, with no identified high-affinity receptor ^[1]. LL-37 — electrostatic membrane interaction plus receptor-associated host-cell effects. KPV — transporter-mediated uptake and NF-κB inhibition. Thymosin β4 — actin sequestration.

Regulatory position

Thymosin alpha-1 is the only compound in this group approved as a medicine anywhere, and it is not approved in the United States ^[4]. LL-37 has reached phase 2b. Thymosin β4 has completed phase 3 in an ophthalmic indication. KPV has no registered human trial. Approval is specific to a compound, an indication and a jurisdiction.

Chemical & Molecular Characteristics

Thymosin alpha-1 is a 28-residue linear peptide, N-terminally acetylated, sequence SDAAVDTSSEITTKDLKEKKEVVEEAEN. PubChem CID 16130571, CAS 62304-98-7, UNII W0B22ISQ1C, molecular formula C129H215N33O55, average mass 3108.3 g/mol — the same figure carried in the supplier catalog.

The acetyl group is part of the molecule and not in the string. Single-letter code cannot express N-terminal acetylation, and the registers describe the acetylated peptide. A synthesis that omitted the acetyl would give a substance 42 daltons lighter, which is resolvable by mass spectrometry and invisible to a sequence check.

The composition is strongly acidic. Counting ionisable side chains gives six aspartates and five glutamates against four lysines and no arginine or histidine. The peptide is therefore markedly negatively charged at physiological pH — the opposite of the cationic host-defence peptides elsewhere in this library, and the reason its behaviour in solution, on ion-exchange columns and in mass spectrometry differs from theirs.

Impurities are sequence-related. A 28-mer made by solid-phase synthesis accumulates deletion, insertion and side-chain modification products that differ from the target peptide by one residue or one functional group, which places them very close in mass and often close in retention time. Liquid chromatography with high-resolution mass spectrometry has been applied specifically to identifying and quantifying these in thymalfasin ^[8]. The practical implication is that an HPLC purity percentage alone characterises this peptide weakly; an orthogonal identification method carries information the percentage does not.

Nomenclature, once more. Thymalfasin is the International Nonproprietary Name; ZADAXIN is the principal brand; "Tα1" and "TA1" are the common abbreviations in the literature; "thymosin fraction 5" refers to the original crude thymic preparation from which the peptide was isolated and is not the same substance.

Analytical Specifications

Analytical figures are lot-specific. Fields the catalog does not carry for the current lot are omitted rather than filled with a typical value. The certificate of analysis and the safety data sheet for the exact lot supplied are provided with a laboratory order; no purity figure on this page is a substitute for that document.

Frequently Asked Questions

Scientific References

1. Romani L, Bistoni F, Gaziano R, et al.. Thymosin alpha 1 activates dendritic cells for antifungal Th1 resistance through toll-like receptor signaling Blood; 2004. PMID 14982877 doi:10.1182/blood-2003-11-4036
2. Romani L, Bistoni F, Perruccio K, et al.. Thymosin alpha1 activates dendritic cell tryptophan catabolism and establishes a regulatory environment for balance of inflammation and tolerance Blood; 2006. PMID 16741252 doi:10.1182/blood-2006-02-004762
3. Yang YF, Zhao W, Zhong YD, et al.. Comparison of the efficacy of thymosin alpha-1 and interferon alpha in the treatment of chronic hepatitis B: a meta-analysis Antiviral research; 2008. PMID 18078676 doi:10.1016/j.antiviral.2007.10.014
4. Goldstein AL, Goldstein AL. From lab to bedside: emerging clinical applications of thymosin alpha 1 Expert opinion on biological therapy; 2009. PMID 19392576 doi:10.1517/14712590902911412
5. Maio M, Mackiewicz A, Testori A, et al.. Large randomized study of thymosin alpha 1, interferon alfa, or both in combination with dacarbazine in patients with metastatic melanoma Journal of clinical oncology : official journal of the American Society of Clinical Oncology; 2010. PMID 20194853 doi:10.1200/JCO.2009.25.5208
6. 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 Critical care (London, England); 2013. PMID 23327199 doi:10.1186/cc11932
7. Peng D, Xing HY, Li C, et al.. The clinical efficacy and adverse effects of Entecavir plus Thymosin alpha-1 combination therapy versus Entecavir Monotherapy in HBV-related cirrhosis: a systematic review and meta-analysis BMC gastroenterology; 2020. PMID 33076834 doi:10.1186/s12876-020-01477-8
8. Cheng Y, Wu P, Kan Y, et al.. Identification and determination of structurally related peptide impurities in thymalfasin by liquid chromatography-high-resolution mass spectrometry Analytical and bioanalytical chemistry; 2022. PMID 36207535 doi:10.1007/s00216-022-04336-5
9. Wu J, Pei F, Zhou L, et al.. The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial BMJ (Clinical research ed.); 2025. PMID 39814420 doi:10.1136/bmj-2024-082583
10. Gu B, Zhou Y, Nie Y, et al.. Efficacy of thymosin α1 for sepsis: a systematic review and meta-analysis of randomized controlled trials Frontiers in cellular and infection microbiology; 2025. PMID 40969554 doi:10.3389/fcimb.2025.1673959
11. Naing C, Ni H, Aung HH, et al.. Thymosin-ɑ1 for people with chronic hepatitis B The Cochrane database of systematic reviews; 2026. PMID 42713852 doi:10.1002/14651858.CD014610.pub2
12. Efficacy of Thymosin alpha1 for Severe Sepsis 2008. NCT00711620
13. Thymosin Alpha 1 in the Prevention of Pancreatic Infection Following Acute Necrotizing Pancreatitis 2018. NCT02473406
14. The Efficacy and Safety of Ta1 for Sepsis 2016. NCT02867267
15. Thymosin-alpha 1 for Adjuvant Treatment After Radical Resection of High-risk Stage II and III Colorectal Cancer 2021. NCT05086614

Every identifier above is resolved against PubMed, Crossref or ClinicalTrials.gov at build time, and the title returned by the register is compared with the title stored here. A page does not publish if a reference fails to resolve.

Research-Use Information

For in vitro research use only. This material is a laboratory reagent. It is not a drug, food, dietary supplement, or cosmetic and is not for human or veterinary use, including ingestion, injection, or any other administration. No information on this page describes or implies any effect in humans or animals. Sold only to researchers under our Terms of Sale.

Related laboratory reagent: Thymosin Alpha-1 specifications and lot documentation