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TB-500 and thymosin beta-4: what the research literature shows

TB-500 is a product name, and it does not always mean the same molecule. Analytical laboratories identify it as a seven-residue synthetic fragment of thymosin beta-4, one of the thymic peptides, and at least one recent paper uses the name for synthetic thymosin beta-4 itself.12 Most published research was done on the full 43-residue protein, and one analytical paper states that the biological effects of TB-500 have not been documented, so this page sorts the literature by molecule.3

  • Horizon Peptides editorial
  • Updated
  • 10 min read
  • 29 sources

Evidence cited on this page

  • 4 cell studies
  • 8 animal studies
  • 4 human studies
  • 1 review
  • 1 chemistry study
  • 11 other sources
On this page9 sections

Key points

  • Thymosin beta-4 is a 43-residue polypeptide that binds single units (monomers) of actin, the protein of the cell’s internal filaments, one-to-one and keeps them from polymerizing.45
  • Analytical laboratories identify TB-500 as Ac-LKKTETQ, an acetylated copy of residues 17 to 23 of that protein.13
  • Every clinical trial and most of the animal work described here used the full protein.678
  • What we found on the short fragment is cell and tissue assays, one aged-mouse wound experiment, a corneal hydrogel study, analytical chemistry and a rat tendon study that does not state its sequence.234910
  • Human trials of thymosin beta-4 are mostly small, and two of the published ones did not reach significance on their primary endpoints.61112
  • We found no published human study of the fragment, and the FDA says it “has not identified any human exposure data” on drug products containing it.13

What it is

Three things behind one name

Review Thymosin beta-4 is the natural molecule, first isolated from calf thymus and at first thought to be a thymic hormone.5 It was later found in large amounts in many cell types, and a review of the family concludes that it is not really a thymic hormone.14 It is a 43-residue polypeptide of about 5 kDa.4

Cell study Its actin-binding region includes a short stretch in the middle of the chain, mapped to residues 17 to 22; later papers call the seven residues LKKTETQ, positions 17 to 23, the actin-binding domain.1915

TB-500 is a commercial name. A racing laboratory that analyzed a veterinary preparation sold under it reported that the key ingredient was LKKTETQ with an acetyl group added to the N-terminus.1 A later metabolism study and PubChem define TB-500 as Ac-LKKTETQ, and the FDA gives TB-500 as another name for the LKKTETQ fragment.31316

Property Thymosin beta-4 TB-500 (analytical literature)
Length 43 residues 7 residues
Sequence Ac-SDKPDMAEIEKFDKSKLKKTETQEKNPLPSKETIEQEKQAGES Ac-LKKTETQ
Formula C212H350N56O78S C38H68N10O14
Molecular weight 4963 g/mol 889.0 g/mol
PubChem CID 16132341 (listed as timbetasin) 62707662
CAS number 77591-33-4 885340-08-9

Values are from the two PubChem records.1617

How it is studied

Three kinds of experiment recur, on different rungs of the evidence ladder.

  • Cell study Bench and cell work: actin polymerization assays, endothelial cell migration and vessel-sprouting assays, and mass spectrometry of the peptide and its breakdown products.345
  • Animal study Injury models: skin wounds in diabetic and aged mice, coronary artery ligation in mice, cardiopulmonary bypass in pigs, alkali burns of the mouse cornea and tendon repair in rats.278918
  • Human study Clinical trials of full-length thymosin beta-4 in healthy volunteers, venous ulcers, dry eye and neurotrophic keratopathy, a disease of the corneal surface.6111920

What the literature reports

Actin sequestration (thymosin beta-4)

Cell study A peptide purified from human platelets as an actin-sequestering factor turned out to have the same sequence as thymosin beta-4, which formed a 1:1 complex with actin monomers and inhibited their polymerization into filaments.5

Review A later review describes beta-thymosins as the main peptides holding actin monomers in reserve in most vertebrate cells, binding loosely enough to release actin quickly, and notes that very little is known about how the effects attributed to them outside the cell are produced.14

Cell study A mapping study with chemically synthesized full-length variants found two parts of the chain holding actin: an N-terminal segment (residues 1 to 16), which had to form a helix, and a six-residue motif at residues 17 to 22.15 It used full-length variants, so it does not test the seven-residue fragment on its own.15

Cell migration and vessel sprouting (both molecules)

Cell study In endothelial cell migration assays and chick aortic arch sprouting assays, thymosin beta-4 and a seven-residue peptide carrying the actin-binding motif showed near-identical activity, while peptides lacking any part of the motif were inactive.4

Cell study In a fibroblast wound-closure assay of the acetylated form sold as TB-500, the parent peptide Ac-LKKTETQ did not differ significantly from control; only one of its breakdown products, Ac-LKKTE, did.3 The authors suggest that activity reported for TB-500 may come from that metabolite, not from the parent peptide.3

Skin wound models (mostly thymosin beta-4)

Animal study In full-thickness skin wounds, thymosin beta-4 was followed by more wound contracture and collagen deposition than in controls in both diabetic and aged mice, with more migration of keratinocytes (skin cells) in the aged mice only.9 The same paper holds the only wound experiment we found on the short sequence: synthetic LKKTETQ gave repair in aged mice comparable to the parent molecule.9 A later paper assigns that work to the unacetylated sequence, not to the acetylated TB-500.3

Cardiac models (thymosin beta-4)

Animal study In mice, thymosin beta-4 given after coronary artery ligation was followed by higher activity of two signalling enzymes, integrin-linked kinase and Akt, in the heart and greater early survival of heart muscle cells, and the authors reported better cardiac function.7

Animal study A later paper recalls an earlier report in which cells of the epicardium, the heart’s outer layer, became heart muscle cells in mice pretreated with thymosin beta-4 before an infarction.21 Its own experiment gave the peptide after the infarction and traced the cells genetically: the epicardium thickened and capillary density rose, but its cells did not become heart muscle.21

Animal study In pigs undergoing cardiopulmonary bypass with aortic cross-clamping, cell death, cardiac function and myocardial blood flow did not differ between animals given thymosin beta-4 and those given vehicle.18

Corneal models

Animal study In mouse corneas injured with alkali, eyes treated with thymosin beta-4 regrew their surface cell layer (re-epithelialized) faster than saline-treated controls, with fewer infiltrating white blood cells (neutrophils) at seven days and lower transcript levels of several inflammatory mediators.8

Animal study A 2025 materials study built the LKKTETQ sequence into a self-assembling hydrogel conjugate, not the free peptide, and described the sequence as not previously explored for corneal disease.10 It was tested on human corneal cells in culture and in an alkali burn model, where the authors reported faster regrowth of the surface layer and less inflammation.10

Tendon repair (material labelled TB-500)

Animal study In a rat Achilles tendon transection-and-repair model, the group given TB-500, which the abstract calls synthetic thymosin beta-4 without giving a sequence, had a higher load to failure and lower histological degeneration scores than controls at four weeks.2 Combining it with BPC-157 added nothing over either peptide alone, and the authors call the findings exploratory.2

Tumour models (thymosin beta-4 expression)

Animal study Mouse melanoma cells engineered to overexpress the thymosin beta-4 gene formed larger tumours and more lung metastases in mice than control cells, with more cell migration and more blood vessels in the tumours; no peptide was added from outside.22

Human evidence

We found no human evidence for the seven-residue fragment: no published trial, and the FDA states that it has not identified human exposure data on drug products containing it.13 Every trial below used full-length thymosin beta-4.

  • Human study Phase 1, healthy volunteers. Four cohorts of ten healthy volunteers were given synthetic thymosin beta-4 or placebo once and then repeatedly, in amounts rising from cohort to cohort; adverse events were infrequent, mild or moderate, and none was serious or stopped the escalation.19
  • Human study Venous ulcers. A double-blind, placebo-controlled phase 2 trial randomized 73 patients; the authors judged safety comparable to placebo and called the efficacy results suggestive at one tested concentration, with no statistical comparison in the abstract.20
  • Human study Dry eye. In a phase 2 trial of an ophthalmic solution in 72 subjects, neither primary endpoint differed significantly from placebo, although some secondary measures did.11 A phase 3 trial, ARISE-3, enrolled 700 participants; the registry shows nearly identical mean changes in both primary measures in the two arms and posts no statistical analysis.23
  • Human study Neurotrophic keratopathy. In a phase 3 trial that enrolled 18 patients, complete closure of the corneal defect at four weeks was recorded in 6 of 10 treated and 1 of 8 placebo patients, which was not statistically significant (p = 0.0656).6 Three of the six authors were employees of the sponsor or its parent company.6 The registry lists that trial as terminated for a business decision, and a second trial, SEER-2, as recruiting in a record last updated in December 2025.1224
  • Human study Acute myocardial infarction. A recombinant form has reached phase 2 in China; the registry lists a 90-participant trial as completed, with no results posted.25

Regulatory status

  • Canada. A search of Health Canada’s Drug Product Database on 8 October 2026 for thymosin and timbetasin as active ingredients returned no products.26
  • United States. On the same date, the same search of the FDA’s Drugs@FDA data returned no matches, and the September 2026 data file of the Purple Book, the FDA’s list of licensed biological products, had no entry for either name.2728 An FDA compounding page, current as of 22 April 2026, lists the fragment LKKTETQ, with TB-500 as its other name, among bulk substances once placed in category 2 of its interim policies (substances that may present significant safety risks) and later withdrawn by their nominators; it cites a possible unwanted immune response (immunogenicity) from aggregation and peptide-related impurities.13
  • Sport. As displayed on 8 October 2026, the World Anti-Doping Agency’s Prohibited List names thymosin beta-4 and its derivatives, with TB-500 as the example, among growth factors prohibited at all times under section S2.3.29

Material sold on this site is for laboratory research use only.

In the laboratory

TB-500 is supplied here as a lyophilized (freeze-dried) powder in sealed vials, alone and in a two-peptide vial with BPC-157. A pre-mixed liquid format is also listed.

Because the name covers two molecules, identity comes first. The two differ more than fivefold in mass, so a mass spectrum, where a batch document gives one, shows which molecule a lot contains.1617 Our guide to reading a certificate of analysis shows where to look, and batch documents are posted on the Lab Results page when they exist.

The two sequences also differ in the residues usually watched for oxidation: thymosin beta-4 has one methionine, at position 6, and a review mentions an oxidized form of the protein, while the fragment has no methionine, cysteine or tryptophan.141617 Oxidation and the other routes are explained in peptide stability and degradation.

Cell study A doping-control study followed the breakdown of Ac-LKKTETQ in human serum, enzyme preparations and urine from rats given the peptide, and reports shorter acetylated pieces that include Ac-LK, Ac-LKK and Ac-LKKTE.3

Temperature, light and moisture are covered in the peptide storage guide.

Compound facts

ClassSynthetic peptide derived from thymosin beta-4, an actin-binding polypeptide

Frequently asked questions

Is TB-500 the same as thymosin beta-4?

No: thymosin beta-4 is a 43-residue natural polypeptide, and the TB-500 identified by analytical laboratories is a seven-residue acetylated fragment of it, Ac-LKKTETQ.14 At least one paper uses the label for synthetic thymosin beta-4 without giving a sequence, so the sequence or the mass has to be checked.2

Has TB-500 been tested in people?

We found no published human trial of the seven-residue fragment, and the FDA states that it has not identified human exposure data on drug products containing it.13

Human study Full-length thymosin beta-4 has been through a phase 1 study in healthy volunteers and phase 2 and 3 trials in skin ulcers and eye disease.61920

Is thymosin beta-4 an approved medicine?

Not in the sources we checked: on 8 October 2026, Health Canada’s Drug Product Database, the FDA’s Drugs@FDA data and the September 2026 Purple Book data file listed no product with thymosin or timbetasin as an active ingredient.262728

How can a laboratory tell which molecule a vial holds?

By mass: PubChem gives 889.0 g/mol for the fragment and 4963 g/mol for the full protein, so a mass spectrum tells them apart.1617

References

Every record links to its PubMed entry or its source. The label under each one names the kind of work it is.

  1. Ho EN, Kwok WH, Lau MY, et al. Doping control analysis of TB-500, a synthetic version of an active region of thymosin β₄, in equine urine and plasma by liquid chromatography-mass spectrometry. J Chromatogr A. 2012.

    Chemistry studyLC-MS analysis of a veterinary preparation and of urine and plasma from horses given it

    PubMed 23084823 (opens in a new tab)abcde

  2. Biçer O, Adanir O, Güleryüz Y, et al. Effects of BPC-157 and TB-500 on Achilles tendon healing in rats: A histopathological and biomechanical study. Jt Dis Relat Surg. 2026.

    Animal studyAchilles tendon transection and repair in 32 rats, four groups, assessed at four weeks

    PubMed 42542926 (opens in a new tab)abcdef

  3. Rahaman KA, Muresan AR, Min H, et al. Simultaneous quantification of TB-500 and its metabolites in in-vitro experiments and rats by UHPLC-Q-Exactive orbitrap MS/MS and their screening by wound healing activities in-vitro. J Chromatogr B Analyt Technol Biomed Life Sci. 2024.

    Cell studyLC-MS metabolism study in human serum, enzyme systems and rat urine; fibroblast cytotoxicity and wound-closure assays

    PubMed 38382158 (opens in a new tab)abcdefghij

  4. Philp D, Huff T, Gho YS, et al. The actin binding site on thymosin beta4 promotes angiogenesis. FASEB J. 2003.

    Cell studyEndothelial cell migration and adhesion assays and chick aortic arch sprouting assays

    PubMed 14500546 (opens in a new tab)abcdefg

  5. Safer D, Elzinga M, Nachmias VT. Thymosin beta 4 and Fx, an actin-sequestering peptide, are indistinguishable. J Biol Chem. 1991.

    Cell studyBiochemistry with purified platelet peptide and muscle actin

    PubMed 1999398 (opens in a new tab)abcd

  6. Sosne G, Kleinman HK, Springs C, et al. 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.

    Human studyRandomized, double-masked, placebo-controlled phase 3 trial in 18 patients with neurotrophic keratopathy

    PubMed 36613994 (opens in a new tab)abcdefg

  7. Bock-Marquette I, Saxena A, White MD, et al. Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature. 2004.

    Animal studyEmbryonic and postnatal cardiac cell cultures; coronary artery ligation in mice

    PubMed 15565145 (opens in a new tab)abcd

  8. Sosne G, Szliter EA, Barrett R, et al. Thymosin beta 4 promotes corneal wound healing and decreases inflammation in vivo following alkali injury. Exp Eye Res. 2002.

    Animal studyAlkali injury of the mouse cornea

    PubMed 11950239 (opens in a new tab)abc

  9. Philp D, Badamchian M, Scheremeta B, et al. Thymosin beta 4 and a synthetic peptide containing its actin-binding domain promote dermal wound repair in db/db diabetic mice and in aged mice. Wound Repair Regen. 2003.

    Animal studyFull-thickness dermal wounds in rats, db/db diabetic mice and aged mice

    PubMed 12581423 (opens in a new tab)abcdef

  10. Lu P, Shan M, Peng C, et al. Alkaline Phosphatase-Triggered Spatiotemporal Repair of Corneal Injury with TB500 Peptide Hydrogel. ACS Appl Mater Interfaces. 2025.

    Animal studySelf-assembling peptide hydrogel carrying the LKKTETQ sequence; human corneal cell cultures and an alkali burn model (species not given in the abstract)

    PubMed 41359360 (opens in a new tab)abcd

  11. 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.

    Human studySingle-centre, randomized, double-masked, placebo-controlled phase 2 trial in 72 subjects with dry eye

    PubMed 26056426 (opens in a new tab)abcd

  12. ClinicalTrials.gov, U.S. National Library of Medicine; sponsor ReGenTree, LLC. Assessment of the Safety and Efficacy Study of RGN-259 Ophthalmic Solutions for Neurotrophic Keratopathy: SEER-1 (NCT02600429), primary outcome and termination status. Accessed 8 October 2026.

    Source

    clinicaltrials.gov (opens in a new tab)abc

  13. U.S. Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (content current as of 22 April 2026). Accessed 8 October 2026.

    Source

    fda.gov (opens in a new tab)abcde

  14. Hannappel E. beta-Thymosins. Ann N Y Acad Sci. 2007.

    ReviewNarrative review of the beta-thymosin family

    PubMed 17468232 (opens in a new tab)abc

  15. Van Troys M, Dewitte D, Goethals M, et al. The actin binding site of thymosin beta 4 mapped by mutational analysis. EMBO J. 1996.

    Cell studyChemically synthesized full-length thymosin beta-4 variants tested for actin binding

    PubMed 8617195 (opens in a new tab)abcd

  16. National Center for Biotechnology Information, U.S. National Library of Medicine. PubChem Compound Summary for CID 62707662 (synonyms include TB-500 and Ac-Leu-Lys-Lys-Thr-Glu-Thr-Gln-OH). Accessed 8 October 2026.

    Source

    pubchem.ncbi.nlm.nih.gov (opens in a new tab)abcde

  17. National Center for Biotechnology Information, U.S. National Library of Medicine. PubChem Compound Summary for CID 16132341, Timbetasin (synonyms include thymosin beta4). Accessed 8 October 2026.

    Source

    pubchem.ncbi.nlm.nih.gov (opens in a new tab)abcd

  18. Stark CK, Tarkia M, Kentala R, et al. Systemic Dosing of Thymosin Beta 4 before and after Ischemia Does Not Attenuate Global Myocardial Ischemia-Reperfusion Injury in Pigs. Front Pharmacol. 2016.

    Animal studyPigs undergoing cardiopulmonary bypass and aortic cross-clamping, with MRI and PET imaging

    PubMed 27199757 (opens in a new tab)abc

  19. Ruff D, Crockford D, Girardi G, et al. A randomized, placebo-controlled, single and multiple dose study of intravenous thymosin beta4 in healthy volunteers. Ann N Y Acad Sci. 2010.

    Human studyRandomized, placebo-controlled phase 1 study in four cohorts of 10 healthy volunteers

    PubMed 20536472 (opens in a new tab)abc

  20. Guarnera G, DeRosa A, Camerini R. The effect of thymosin treatment of venous ulcers. Ann N Y Acad Sci. 2010.

    Human studyDouble-blind, placebo-controlled phase 2 trial of ascending concentrations in 73 patients with venous stasis ulcers at eight European sites

    PubMed 20536470 (opens in a new tab)abc

  21. Zhou B, Honor LB, Ma Q, et al. Thymosin beta 4 treatment after myocardial infarction does not reprogram epicardial cells into cardiomyocytes. J Mol Cell Cardiol. 2012.

    Animal studyMouse myocardial infarction with genetic lineage tracing of epicardial cells

    PubMed 21907210 (opens in a new tab)abc

  22. Cha HJ, Jeong MJ, Kleinman HK. Role of thymosin beta4 in tumor metastasis and angiogenesis. J Natl Cancer Inst. 2003.

    Animal studyMouse melanoma cells engineered to overexpress thymosin beta-4, grown as tumours in mice

    PubMed 14625258 (opens in a new tab)↑

  23. ClinicalTrials.gov, U.S. National Library of Medicine; sponsor ReGenTree, LLC. Assessment of the Safety and Efficacy of RGN-259 Ophthalmic Solutions for Dry Eye Syndrome: ARISE-3 (NCT03937882), with results posted 28 August 2026. Accessed 8 October 2026.

    Source

    clinicaltrials.gov (opens in a new tab)↑

  24. ClinicalTrials.gov, U.S. National Library of Medicine; sponsor ReGenTree, LLC. Assessment of the Safety and Efficacy of 0.1% RGN-259 Ophthalmic Solution for the Treatment of NK: SEER-2 (NCT05555589), listed as recruiting; record last updated 23 December 2025. Accessed 8 October 2026.

    Source

    clinicaltrials.gov (opens in a new tab)↑

  25. ClinicalTrials.gov, U.S. National Library of Medicine; sponsor Beijing Northland Biotech. Co., Ltd.. Efficacy and Safety Study of Thymosin Beta 4 in Patients With Acute Myocardial Infarction (NCT05984134). Accessed 8 October 2026.

    Source

    clinicaltrials.gov (opens in a new tab)↑

  26. Health Canada. Drug Product Database: active ingredient search for thymosin, no products returned; the same search for timbetasin also returned none. Accessed 8 October 2026.

    Source

    health-products.canada.ca (opens in a new tab)ab

  27. U.S. Food and Drug Administration. Drugs@FDA data (openFDA drugsfda endpoint): search for thymosin as an active ingredient, no matches; the same search for timbetasin also returned none. Accessed 8 October 2026.

    Source

    api.fda.gov (opens in a new tab)ab

  28. U.S. Food and Drug Administration. Purple Book: Database of Licensed Biological Products, September 2026 data download: no entry containing thymosin or timbetasin. Accessed 8 October 2026.

    Source

    purplebooksearch.fda.gov (opens in a new tab)ab

  29. World Anti-Doping Agency. The Prohibited List, section S2.3 (growth factors and growth factor modulators), as displayed on 8 October 2026. Accessed 8 October 2026.

    Source

    wada-ama.org (opens in a new tab)↑

Written by Horizon Peptides editorial. Checked against its sources on .

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