what is the difference
Thymosin alpha-1 and thymosin beta-4
Two molecules that share a word because of where they were first isolated, with trial programmes in fields that do not touch: sepsis and infection for one, the surface of the eye for the other.
Thymosin alpha-1 is a 28 amino acid peptide that acts as an immune signal, given as a medicine in more than thirty countries under the name thymalfasin and carrying the deepest trial record in this catalog outside the metabolic group. Thymosin beta-4 is a 43 residue protein with a completely different job: it binds actin, the protein filament that gives a cell its shape and lets it move, and it is the parent molecule of the product sold as TB-500 [7].
The word they share came from a preparation. Both were pulled out of thymus tissue extracts in the era when peptides were named for the organ they were isolated from, and the name records that address rather than any shared structure or function. What follows from that is the whole point of this page: a trial of one is not a trial of the other, and the two programmes have never asked the same question.
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This page reports what has been documented about a compound. It is not medical advice, not a diagnosis, not a dosing protocol, and not a recommendation to obtain or use anything described here. Talk to a licensed clinician about anything concerning your health. Read the full disclaimer.
Reviewed against editorial standards Updated
The short answer
Thymosin alpha-1 and thymosin beta-4 are unrelated molecules with a shared naming prefix. Alpha-1 is 28 amino acids and acts as an immune signal; beta-4 is 43 residues and binds actin inside cells. Neither sequence is a version of the other.
Their trials sit in different fields. Thymosin alpha-1 has been tested in sepsis, chronic hepatitis B and COVID-19, including a phase 3 trial in 1,106 adults [1] [2]. Thymosin beta-4 has been tested on the surface of the eye: phase 2 trials in dry eye and a phase 3 in neurotrophic keratopathy [3] [4] [5]. The registry returned 65 studies under each of alpha-1's two names on 2 August 2026, one record set indexed twice, against 18 under thymosin beta 4 [8].
Side by side
| Property | Thymosin alpha-1 | Thymosin beta-4 |
|---|---|---|
| What it is | A 28 amino acid peptide that acts as an immune signal | A 43 residue protein that binds actin, the filament protein giving a cell its shape and movement |
| What the shared word records | The tissue it was first isolated from, which was a thymus extract | The same tissue, in the same naming era. The prefix is an address, not a structural family |
| Other names | Thymalfasin, the international non-proprietary name, and Zadaxin, a brand name | TB4. The product sold as TB-500 is a seven residue fragment of it, Ac-LKKTETQ, identified by a doping-control laboratory [7] |
| Registered studies | 65 under thymosin alpha 1 and 65 under thymalfasin, one record set indexed under two names. Of them 33 are phase 2, 8 phase 3, 10 phase 4 and 2 observational [8] | 18 under thymosin beta 4, of which 17 registered the protein itself. The eighteenth is the one record naming TB-500, matched because its registered title carries both names [8] |
| Field the trials sit in | Infection and critical care: sepsis, chronic hepatitis B, COVID-19 [1] [2] | The ocular surface: dry eye and corneal wound healing [3] [4] [5] |
| Largest completed trial | TESTS, a multicentre, double blinded, randomised, placebo controlled phase 3 in 1,106 adults with sepsis across 22 centres in China [1] | A randomized, placebo-controlled, double-masked phase 3 in neurotrophic keratopathy, reporting closure of epithelial defects in 6 of 10 treated patients against 1 of 8 on placebo, short of significance [5] |
| Phase 2 record | 33 of the 65 registrations are phase 2, across the infection populations above [8] | Two published phase 2 trials in dry eye: one randomized trial in patients with severe dry eye [3], and one randomized, placebo-controlled trial in 72 subjects run using the controlled adverse environment model, in which neither primary endpoint separated from placebo [4] |
| Route in the published trials | Given systemically to people under a protocol [1] [2] | Given as an ophthalmic solution, applied to the eye [3] [4] [5] |
| US approval status | No approved application returned by a query of FDA's approved-products data on 2 August 2026 [10] | No approved application returned by the same query on the same date [10] |
| WADA 2026 position | Its approval outside the United States makes its position under the S0 class genuinely unsettled, since S0 covers substances with no current approval by any governmental regulatory health authority [9] | Named on the face of the 2026 Prohibited List in class S2.3, growth factors and growth factor modulators, in the entry reading thymosin beta-4 and its derivatives, prohibited at all times [9] |
Why the two get mixed up
The prefix does the damage on its own. Two molecules that begin with the same word read as two members of one family, and in most chemical naming that inference is sound. Here it is not. The thymosins were named in the 1960s and 1970s from fractions of a thymus extract, and the Greek letters distinguish fractions rather than variants of a single sequence. A 28 amino acid immune signal and a 43 residue actin-binding protein ended up sharing a surname because they came out of the same jar.
Product listings compound it by pairing them, one under an immune heading and one under a recovery heading, which invites a reader to treat the better documented molecule as a reference point for the other. The trial counts are the visible symptom: 65 registrations against 18, sitting in a table that says nothing about the fact that no study in either column asked a question the other column would recognise.
There is a second substitution one level down, on the beta side, and it is worth stating here because the two errors stack. What is sold as TB-500 is not thymosin beta-4. A doping-control laboratory that analysed the product identified Ac-LKKTETQ, the acetylated 17 to 23 fragment, seven residues long against the parent's 43 [7]. So a reader can move from a phase 3 trial of an eye drop, to a 43 residue parent protein, to a seven residue fragment sold for tendon recovery, in three steps, without any of the steps being flagged.
What the published record covers for each
The two programmes do not overlap at any point, so the honest comparison is what each one measured. For thymosin alpha-1 the largest result is TESTS, a multicentre, double blinded, randomised, placebo controlled phase 3 trial in 1,106 adults with sepsis across 22 centres in China, in which death from any cause at 28 days occurred in 23.4 percent of the treated group and 24.1 percent of placebo, a hazard ratio of 0.99, with no secondary outcome separating [Human RCT] [1]. Its longer-standing use is chronic hepatitis B, pooled in a 2008 meta-analysis of four randomized trials in 199 patients against interferon alpha [Human RCT] [2].
For thymosin beta-4 the published human work is ophthalmic and it is small. Two phase 2 trials in dry eye were published in 2015: one randomized trial in patients with severe dry eye [3], and one randomized, placebo-controlled trial in 72 subjects conducted using the controlled adverse environment model, a standardised chamber that provokes dry eye symptoms under fixed conditions, in which neither primary endpoint separated from placebo at the primary visit [4]. Both delivered the peptide as an eye drop [Human RCT].
The furthest that programme reached is a randomized, placebo-controlled, double-masked phase 3 in neurotrophic keratopathy, which reported closure of epithelial defects in 6 of 10 treated patients against 1 of 8 on placebo, a difference short of statistical significance in a trial of that size [Human RCT] [5]. An eighteen patient phase 3 is unusual, and it is a consequence of the condition being rare rather than of the programme being casual.
A frequently cited 2018 article in Expert Opinion on Biological Therapy traces this compound from the laboratory bench to the clinic. PubMed indexes it as a journal article, a review and a personal narrative, and it is written by an investigator on the trials above [6]. It is useful for the development history and it is not a study, so nothing here treats it as evidence of an effect.
What none of the beta-4 work covers is the use the fragment sold from it is marketed for. Every completed trial in that column was run on the surface of an eye. No registered trial has tested thymosin beta-4, or the seven residue fragment taken from it, in a human tendon or muscle injury.
Our takeThe shared word is an accident of which jar each peptide came out of. One programme has taken its molecule into more than a thousand people with sepsis, the other has taken its molecule onto eighteen corneas, and no result in either column has anything to say about the other.
Frequently asked questions
Are thymosin alpha-1 and thymosin beta-4 related?
Only by name. Thymosin alpha-1 is 28 amino acids and acts as an immune signal. Thymosin beta-4 is 43 residues and binds actin, the filament protein that gives a cell its shape. The shared word records that both were isolated from thymus tissue preparations in the same naming era, and the Greek letters distinguish extract fractions rather than versions of one sequence.
Do their trial counts add together?
No. On 2 August 2026 the registry returned 65 studies under thymosin alpha 1 and 65 under thymalfasin, which is one record set indexed under two names for one molecule, and 18 under thymosin beta 4, seventeen of which registered the protein and the eighteenth being the single record naming TB-500 [8]. Two molecules, two programmes, two fields.
What have the thymosin beta-4 trials actually tested?
The surface of the eye. Two randomized phase 2 trials in dry eye, one of them run in the controlled adverse environment chamber [3] [4], and a randomized, placebo-controlled, double-masked phase 3 in neurotrophic keratopathy that reported closure of epithelial defects in 6 of 10 treated patients against 1 of 8 on placebo, short of significance [5]. All of them delivered it as an ophthalmic solution.
Is TB-500 the same as thymosin beta-4?
No. A doping-control laboratory that analysed the product sold as TB-500 identified Ac-LKKTETQ, the acetylated 17 to 23 fragment, seven residues long against the parent protein's 43 [7]. A trial of the 43 residue parent is evidence about the parent. The fragment has its own evidence review on this site, graded from its own claim rows.
Why is one of the references described as a review rather than as a study?
Because that is how PubMed indexes it: the 2018 Expert Opinion on Biological Therapy article on thymosin beta-4 and the eye carries the publication types journal article, review and personal narrative, and it is written by an investigator on the trials it describes [6]. It is cited here for the development history. A review is not a new measurement, and this site does not let one carry an effect claim on its own.
How do the two sit on the WADA Prohibited List?
Differently. Thymosin beta-4 is named on the face of the 2026 list in class S2.3, growth factors and growth factor modulators, in the entry reading thymosin beta-4 and its derivatives, prohibited at all times [9]. Thymosin alpha-1 is not named, and its position under the S0 catch-all is unsettled, because S0 covers substances with no current approval by any governmental regulatory health authority and thymosin alpha-1 holds approvals elsewhere.
References
- Wu J, Pei F, Zhou L, Li W, Sun R, Li Y, Wang Z, He Z, Zhang X, Jin X, Long Y, Cui W, Wang C, Chen E, Zeng J, Yan J, Lin Q, Zhou F, Huang L, Shang Y, Duan M, Zheng W, Zhu D, Kou Q, Zhang S, Liu Y, Yao C, Shang M, Peng S, Zhou Q, Cheng KK, Guan X, TESTS study collaborator group. The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial. BMJ. 2025. PMID 39814420 DOI 10.1136/bmj-2024-082583
- Yang YF, Zhao W, Zhong YD, Yang YJ, Shen L, Zhang N, Huang P. Comparison of the efficacy of thymosin alpha-1 and interferon alpha in the treatment of chronic hepatitis B: a meta-analysis. Antiviral Res. 2008. PMID 18078676 DOI 10.1016/j.antiviral.2007.10.014
- Sosne G, Dunn SP, Kim C. Thymosin β4 significantly improves signs and symptoms of severe dry eye in a phase 2 randomized trial. Cornea. 2015. PMID 25826322 DOI 10.1097/ICO.0000000000000379
- Sosne G, Ousler GW. Thymosin beta 4 ophthalmic solution for dry eye: a randomized, placebo-controlled, Phase II clinical trial conducted using the controlled adverse environment (CAE™) model. Clin Ophthalmol. 2015. PMID 26056426 DOI 10.2147/OPTH.S80954
- Sosne G, Kleinman HK, Springs C, Gross RH, Sung J, Kang S. 0.1% RGN-259 (Thymosin ß4) Ophthalmic Solution Promotes Healing and Improves Comfort in Neurotrophic Keratopathy Patients in a Randomized, Placebo-Controlled, Double-Masked Phase III Clinical Trial. Int J Mol Sci. 2022. PMID 36613994 DOI 10.3390/ijms24010554
- Sosne G. Thymosin beta 4 and the eye: the journey from bench to bedside. Expert Opin Biol Ther. 2018. PMID 30063853 DOI 10.1080/14712598.2018.1486818 Indexed by PubMed as a review and a personal narrative, not as a study
- Esposito S, Deventer K, Goeman J, Van der Eycken J, Van Eenoo P. Synthesis and characterization of the N-terminal acetylated 17-23 fragment of thymosin beta 4 identified in TB-500, a product suspected to possess doping potential. Drug Test Anal. 2012. PMID 22962027 DOI 10.1002/dta.1402
- US National Library of Medicine, ClinicalTrials.gov. Registry counts run through API v2 on 2 August 2026. Thymalfasin returned 65 studies and thymosin alpha 1 returned 65, being one record set indexed under two names. Thymosin beta 4 returned 18 and an intervention search for TB-500 returned 1, which is one of those same 18 rather than an additional record. Re-confirmed against a full API read on 9 August 2026. ClinicalTrials.gov. 2026. Registry search
- World Anti-Doping Agency. The 2026 Prohibited List, international standard, effective 1 January 2026. WADA. 2026. Prohibited List
- US Food and Drug Administration. Drugs@FDA approved products data, queried through the openFDA drug/drugsfda endpoint on 2 August 2026 for thymosin alpha-1, thymalfasin and thymosin beta-4 as active ingredients. No approved application was returned for any of them. openFDA. 2026. Query endpoint