Scientifically reviewed by Dr Stephan Hansberg
Thymosin beta-4: structure, research and legal status (2026)
Thymosin beta-4 is a 43-amino-acid actin-binding peptide found in most human cells. Its identity data, how it was discovered, what has been studied in cell, animal and human models, trial status and where it stands with the FDA, MHRA, TGA and WADA in 2026.
Key takeaways
- •Thymosin beta-4 is a naturally occurring, N-terminally acetylated peptide of 43 amino acids (about 4963 g/mol), encoded in humans by the TMSB4X gene.
- •Its best-established role is binding monomeric G-actin, which makes it the main actin-sequestering peptide in many cell types.
- •Most published work is in cell and animal models; the furthest human programme is RGN-259, an eye-drop formulation that has been through Phase 2 and Phase 3 trials.
- •It is not an approved medicine in the US, UK or Australia. Australia lists it by name in Schedule 4, and WADA prohibits it at all times under S2.
- •TB-500 is not the same molecule: it is a 7-amino-acid acetylated fragment (residues 17 to 23). Celyfe pens contain TB-500, not full-length thymosin beta-4.
What is thymosin beta-4?
Thymosin beta-4 (often written Tβ4) is a small, naturally occurring peptide of 43 amino acids that binds monomeric actin inside cells. It was first sequenced from calf thymus extracts in 1981, which is where the name comes from, but it is now known to be present in most vertebrate tissues rather than being specific to the thymus.
In research it is studied mainly as a regulator of the actin cytoskeleton, and, in cell and animal models, in areas such as cell migration, wound models, cardiac injury models and the ocular surface. It is not an approved medicine anywhere we could identify, and it is a different molecule from TB-500, the short synthetic fragment that is widely sold under a similar name.
Identity at a glance
The identifiers below were checked against PubChem and UniProt. The molar mass is the PubChem computed value for the acetylated peptide.
| Property | Thymosin beta-4 |
|---|---|
| Aliases | Tβ4, thymosin beta 4, TMSB4X gene product; RGN-259 (ophthalmic formulation in clinical development); NL005 (recombinant human form in clinical development) |
| Sequence (43 aa) | Ac-SDKPDMAEIEKFDKSKLKKTETQEKNPLPSKETIEQEKQAGES |
| Molecular formula | C212H350N56O78S |
| Molar mass | approx. 4963 g/mol |
| CAS number | 77591-33-4 |
| PubChem CID | 16132341 |
| UniProt (human) | P62328 (TYB4_HUMAN) |
| Related fragments | TB-500 = Ac-LKKTETQ (residues 17 to 23); Ac-SDKP = N-terminal tetrapeptide |
Origin and discovery
Thymosin beta-4 was characterised by Allan Goldstein's group in the course of work on thymic extracts: in 1981 Low and Goldstein published the complete amino acid sequence of bovine thymosin beta-4, describing it at the time as a thymic hormone. Two years later a survey across vertebrate classes showed the peptide in a wide range of species and tissues, which shifted the picture away from a thymus-specific hormone.
The key reinterpretation came in 1991, when Safer and colleagues showed that thymosin beta-4 is the same molecule as an actin-sequestering peptide they had been studying, called Fx. In 1992 Cassimeris and colleagues reported that it holds the majority of unpolymerised G-actin in resting human white blood cells. Since then it has been treated primarily as a cytoskeletal regulator, with a separate literature on what it does outside the cell.
What has been studied, by model
The table lists representative published studies, with the model stated for each. Findings in cells or animals describe what was observed under those experimental conditions and do not establish an effect in people.
| Research area | Model | Example study (year, PMID) |
|---|---|---|
| Actin sequestration | Cell / biochemical | Safer et al., J Biol Chem (1991), PMID 1999398 |
| G-actin pool in white blood cells | Human cells | Cassimeris et al., J Cell Biol (1992), PMID 1447300 |
| Full-thickness wound model and keratinocyte migration | Animal (rat) and cell | Malinda et al., J Invest Dermatol (1999), PMID 10469335 |
| Sulfoxide form produced by monocytes | Human cells | Young et al., Nat Med (1999), PMID 10581087 |
| Cardiac cell migration and integrin-linked kinase | Cell and animal (mouse) | Bock-Marquette et al., Nature (2004), PMID 15565145 |
| Active sites in short sequences | Review of cell and animal work | Sosne et al., FASEB J (2010), PMID 20179146 |
| Lung fibroblasts and the Ac-SDKP fragment | Human cells and animal (mouse) | Conte et al., Expert Opin Biol Ther (2015), PMID 26098610 |
| Ocular surface (dry eye) | Human, Phase 2 | Sosne et al., Clin Ophthalmol (2015), PMID 26056426 |
Human trial status
Thymosin beta-4 is one of the few peptides in this group with a registered late-stage clinical programme. The ophthalmic formulation RGN-259 has been tested in dry eye and in neurotrophic keratopathy, and a recombinant form (NL005) has been tested in acute myocardial infarction in China. Registration and completion do not mean approval: none of these programmes had produced an approved product as of October 2026.
| ClinicalTrials.gov ID | Programme | Phase | Status (Oct 2026) |
|---|---|---|---|
| NCT02974907 | RGN-259, dry eye (ARISE-2) | Phase 3 | Completed |
| NCT03937882 | RGN-259, dry eye (ARISE-3) | Phase 3 | Completed |
| NCT02600429 | RGN-259, neurotrophic keratopathy (SEER-1) | Phase 3 | Terminated |
| NCT05555589 | RGN-259, neurotrophic keratopathy (SEER-2) | Phase 3 | Recruiting |
| NCT04555824 | Recombinant thymosin beta-4 (NL005), healthy volunteers | Phase 1 | Completed |
| NCT05984134 | NL005, acute myocardial infarction | Phase 2 | Completed |
| NCT00382174 | Thymosin beta-4, pressure ulcers | Phase 2 | Completed |
Regulatory status in 2026
Thymosin beta-4 has no marketing authorisation as a medicine in the US, UK or Australia. Australia and WADA name it explicitly.
| Authority | Status (checked October 2026) |
|---|---|
| US FDA | Not an approved drug. RGN-259 is investigational. The related fragment TB-500 was reviewed by the Pharmacy Compounding Advisory Committee in July 2026; full-length thymosin beta-4 was not on that agenda. |
| UK MHRA | No UK marketing authorisation. Supplying it as a medicine for human use would fall under the Human Medicines Regulations 2012. |
| AU TGA | Listed by name in Schedule 4 (prescription only) of the Poisons Standard (October 2026 instrument, F2026L01327), as is TB500. |
| WADA 2026 | Prohibited at all times under S2.3 (growth factors and growth factor modulators): "Thymosin-ß4 and its derivatives e.g. TB-500". |
Stability and handling notes
Thymosin beta-4 contains a single methionine at position 6, a residue that oxidises readily to methionine sulfoxide. The oxidised form is not just a degradation product: Young and colleagues described thymosin beta-4 sulfoxide being generated by monocytes in the presence of glucocorticoids. For an analyst, this means a +16 Da species in a mass spectrum may be the sulfoxide, and a certificate should state how identity was confirmed.
At about 4963 g/mol it is also more than five times heavier than TB-500, so mass spectrometry separates the two immediately. That makes identity testing the simplest way to check which molecule a vial actually contains.
Open questions
How an intracellular actin-binding peptide acts outside the cell is still debated, and several of the activities reported for thymosin beta-4 have been mapped to short internal sequences rather than to the whole molecule. Whether the late-stage eye programme will reach approval, and whether findings in rodent cardiac and wound models translate to people, remain open.
Where Celyfe fits
Celyfe does not sell full-length thymosin beta-4. The WOLVERINE Pen (/products/wolverine-pen) contains TB-500 15mg, the acetylated 17 to 23 fragment (C38H68N10O14, 889.0 g/mol, CAS 885340-08-9), together with BPC-157 15mg in a pre-filled 3ml cartridge. Its batch certificate (batch C26071, Analiza Bialek, Wroclaw, HPLC, 99% purity, dated 2 October 2026) is published in the COA library at /coa.
TB-500 15mg is also in the GLOW and KLOW pens; their certificates are being re-issued and are listed in the COA library when published. The comparison guide thymosin beta-4 vs TB-500 sets out the difference in detail.
Sources
Primary and official sources checked October 2026:
- PubChem: Thymosin beta-4, CID 16132341 (pubchem.ncbi.nlm.nih.gov)
- UniProt: P62328, Thymosin beta-4, Homo sapiens (uniprot.org)
- Low TL, Goldstein AL et al. Complete amino acid sequence of bovine thymosin beta 4. Proc Natl Acad Sci USA, 1981. PMID 6940133
- Erickson-Viitanen S et al. Distribution of thymosin beta 4 in vertebrate classes. Arch Biochem Biophys, 1983. PMID 6838210
- Safer D et al. Thymosin beta 4 and Fx, an actin-sequestering peptide, are indistinguishable. J Biol Chem, 1991. PMID 1999398
- Cassimeris L et al. Thymosin beta 4 sequesters the majority of G-actin in resting human polymorphonuclear leukocytes. J Cell Biol, 1992. PMID 1447300
- Malinda KM et al. Thymosin beta-4 in a rat full-thickness wound model. J Invest Dermatol, 1999. PMID 10469335
- Young JD et al. Thymosin beta 4 sulfoxide is an anti-inflammatory agent generated by monocytes in the presence of glucocorticoids. Nat Med, 1999. PMID 10581087
- Bock-Marquette I et al. Thymosin beta4 activates integrin-linked kinase. Nature, 2004. PMID 15565145
- Sosne G et al. Biological activities of thymosin beta4 defined by active sites in short peptide sequences. FASEB J, 2010. PMID 20179146
- Conte E et al. Effects of thymosin beta-4 and its N-terminal fragment Ac-SDKP on TGF-beta-treated human lung fibroblasts and in a mouse model. Expert Opin Biol Ther, 2015. PMID 26098610
- Sosne G et al. Thymosin beta 4 ophthalmic solution for dry eye: a randomized, placebo-controlled, Phase II clinical trial. Clin Ophthalmol, 2015. PMID 26056426
- ClinicalTrials.gov records NCT02974907, NCT03937882, NCT02600429, NCT05555589, NCT04555824, NCT05984134, NCT00382174
- Therapeutic Goods (Poisons Standard, October 2026) Instrument 2026, F2026L01327 (legislation.gov.au)
- WADA: World Anti-Doping Code International Standard, Prohibited List 2026, in force 1 January 2026 (wada-ama.org)
Research use only
Celyfe supplies research peptides for laboratory and research use only. Nothing on this page is guidance on use in humans or animals.
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