Monograph in Tissue-repair & anti-inflammatory peptides
TB-500
Sold as 'thymosin beta-4', TB-500 is actually a seven-residue acetylated fragment of it. The full protein has human trials; the fragment, as FDA notes, has no human exposure data.
Also called Thymosin beta-4 fragment (LKKTETQ) · Ac-LKKTETQ · Thymosin β4 (parent protein) · Timbetasin
Best evidence: Preclinical only
No human data for the LKKTETQ fragment itself. The parent protein, thymosin β4, has phase 2–3 trials (mainly eye drops) — graded separately below.
Not FDA-approved · FDA compounding nomination withdrawn
Residue Editorial Team · updated
What is TB-500?
TB-500 is acetylated LKKTETQ, residues 17–23 of the protein thymosin β4, a region linked to actin binding and wound healing1PubMedDoping 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. Ho EN et al. J Chromatogr A. 2012.,2PubMedSynthesis 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. Esposito S et al. Drug Test Anal. 2012.. Full-length thymosin β4 has been tested in human trials, mostly as eye drops for dry eye3PubMedThymosin beta 4 ophthalmic solution for dry eye: a randomized, placebo-controlled, Phase II clinical trial conducted using the controlled adverse environment (CAE™) model. Sosne G & Ousler GW Clin Ophthalmol. 2015., but FDA states it has found no human exposure data for the fragment, which is not FDA-approved4FDACertain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. U.S. FDA, content current as of 04/22/2026..
Key findings
- Mass-spectrometry analysis of a TB-500 product identified its active ingredient as the N-acetylated 17–23 fragment of thymosin β4 (Ac-LKKTETQ)2.
- The 17–23 segment is described as the active site within thymosin β4 for actin binding, cell migration and wound healing1.
- In a phase 2 dry-eye trial of full-length thymosin β4 eye drops (72 subjects), neither primary endpoint was met, though several secondary endpoints improved3.
- Thymosin β4 eye drops progressed to phase 3 trials for dry eye and neurotrophic keratopathy5PubMedThymosin beta 4 and the eye: the journey from bench to bedside. Sosne G Expert Opin Biol Ther. 2018..
- FDA says it has not identified any human exposure data for products containing the LKKTETQ fragment and lacks important safety information4.
What is TB-500, chemically?
| PubChem CID | 62707662 “Unii-qhk6Z47gtg” · parent: 16132341 “Timbetasin” |
|---|---|
| Formula | C38H68N10O14 (parent C212H350N56O78S) |
| Molecular weight | 889 g/mol (parent 4,963 g/mol) |
| CAS (as listed) | 885340-08-9 |
| FDA UNII | QHK6Z47GTG |
| InChIKey | ADKDNDYYIZUVCZ-ZQNQAVPYSA-N |
| Length | 7 residues |
| Route in trials | Not established in humans (fragment) |
| Mechanism | Fragment (residues 17–23) of thymosin β4, the region linked to actin binding |
- Hydrophobic
- Polar
- Basic (+)
- Acidic (−)
What is TB-500?
Thymosin β4 is a naturally occurring protein. Researchers have identified residues 17–23, LKKTETQ, as the active site responsible for actin binding, cell migration and wound healing1. TB-500 emerged as a veterinary preparation; its key ingredient is that seven-residue segment with an artificial acetyl group on the N-terminus1. Analysis of a TB-500 product by high-resolution mass spectrometry confirmed Ac-LKKTETQ as its content2.
That distinction matters, because the human trial record belongs to the full protein, not the fragment. Figure 1 shows the seven residues of the fragment, from PubChem; the parent protein record is listed separately in the molecular profile6PubChemPubChem compound record: Unii-qhk6Z47gtg. C38H68N10O14 · MW 889 g/mol.,7PubChemPubChem compound record: Timbetasin. C212H350N56O78S · MW 4963 g/mol..
What is the evidence for full-length thymosin β4?
Dry eye. In a single-center, double-masked phase 2 study, 72 people with moderate-to-severe dry eye were randomized to 0.1% thymosin β4 eye drops or placebo for 28 days. Neither primary endpoint — ocular discomfort and inferior corneal staining at day 29 — differed significantly. Several secondary endpoints did: discomfort in the controlled adverse environment chamber on day 28 fell 27% versus placebo, and central and superior corneal staining improved. No adverse events were observed3. A 2018 review described phase 3 trials for dry eye and neurotrophic keratopathy as ongoing5; ClinicalTrials.gov lists several completed phase 3 studies of the eye-drop formulation, RGN-2598TrialAssessment of the Safety and Efficacy of RGN-259 Ophthalmic Solutions for Dry Eye Syndrome: ARISE-3. ReGenTree, LLC · PHASE3 · completed.,9TrialAssessment of the Safety and Efficacy of RGN-259 Ophthalmic Solutions for Dry Eye Syndrome : ARISE-2. ReGenTree, LLC · PHASE3 · completed..
Venous ulcers. A European randomized, double-blind, placebo-controlled, dose-escalation trial of topical thymosin β4 in venous ulcers was described in 2007, planning 72 patients treated for 84 days10PubMedThymosin beta-4 and venous ulcers: clinical remarks on a European prospective, randomized study on safety, tolerability, and enhancement on healing. Guarnera G et al. Ann N Y Acad Sci. 2007..
Heart. Thymosin β4 has been studied in acute myocardial infarction in completed phase 2 trials registered by Beijing Northland Biotech11TrialSafety and Efficacy Study of Thymosin Beta 4 in Patients With Acute Myocardial Infarction.Infarction. Beijing Northland Biotech. Co., Ltd. · PHASE2 · completed.,12TrialEfficacy and Safety Study of Thymosin Beta 4 in Patients With Acute Myocardial Infarction. Beijing Northland Biotech. Co., Ltd. · PHASE2 · completed..
What is the evidence for the fragment itself?
We found no published human study of Ac-LKKTETQ for any health outcome. The human-relevant papers about TB-500 are anti-doping methods: detection in plasma and urine2 and in equine urine and plasma, where its metabolites were mapped1. A recruiting phase 1/2 study lists the 17–23 fragment for cardiovascular biomarkers13TrialTB-500 (Thymosin Beta 4 17-23 Fragment) for Cardiovascular Biomarkers in Stable ASCVD. Hudson Biotech · PHASE1/PHASE2 · recruiting..
Is TB-500 FDA-approved?
| Record | Status | Source |
|---|---|---|
| FDA approval | No approved application Drugs@FDA returned no application for “TB-500”. | openFDA |
| Compounding: nominated, then withdrawn Thymosin beta-4, fragment (LKKTETQ), also known as TB-500 | Withdrawn nomination FDA still lists its safety concerns: “Compounded drugs containing thymosin Beta-4, Fragment (LKKTETQ) may pose risk for immunogenicity for certain routes of administration due to the potential for aggregation as well as peptide-related impurities. FDA has not identified any human exposure data drug products containing Thymosin Beta-4, Fragment. FDA lacks important information regarding any safety issues raised by this drug, including whether it would…” | 4 |
FDA's entry names "Thymosin beta-4, fragment (LKKTETQ), also known as TB-500" among withdrawn compounding nominations. It notes possible immunogenicity from aggregation and impurities, and states that FDA has not identified any human exposure data for drug products containing it and lacks important information on whether it would cause harm in humans4.
What is still unknown?
- Does the fragment reproduce the protein's effects in people? No human data answer this.
- Phase 3 eye-drop results for full-length thymosin β4 should be read in their primary publications as they appear14TrialClinicalTrials.gov registry search: "thymosin beta 4" OR "thymosin beta-4" OR TB-500 OR RGN-259 OR RGN-137. 20 registered studies at fetch..
What effects has TB-500 shown, by body system?
Each row is graded separately using the Residue evidence scale: a compound can carry an A for one use and a D for another.
| System | What was observed | Grade |
|---|---|---|
| Eye (full-length Tβ4) | Phase 2: primary endpoints not met; secondary improvements in discomfort and corneal staining3. | B |
| Skin ulcers (full-length Tβ4) | A randomized, dose-escalation trial of topical Tβ4 in venous ulcers was designed and enrolling in 200710. | C |
| Any effect of TB-500 fragment | No human exposure data identified by FDA4; human detection studies are for anti-doping only2,1. | D |
How much research is there on TB-500?
| Phase | Studies | Breakdown |
|---|---|---|
| Phase 1 | 3 | 2 completed, 0 active or recruiting, 1 stopped, 0 other |
| Phase 2 | 12 | 6 completed, 2 active or recruiting, 4 stopped, 0 other |
| Phase 3 | 5 | 3 completed, 1 active or recruiting, 1 stopped, 0 other |
Compare and continue
- BPC-157 vs TB-500Comparison
- BPC-157Tissue-repair & anti-inflammatory peptides
- GHK-CuTissue-repair & anti-inflammatory peptides
- KPVTissue-repair & anti-inflammatory peptides
Questions readers ask
Is TB-500 the same as thymosin beta-4?
No. TB-500 contains a synthetic, acetylated seven-residue fragment (Ac-LKKTETQ, residues 17–23) of thymosin β4, not the full-length protein2,1. Human trials of thymosin β4 used the full protein3.
Is TB-500 FDA-approved?
No. FDA lists 'Thymosin beta-4, fragment (LKKTETQ), also known as TB-500' among withdrawn compounding nominations and says it has not identified any human exposure data for products containing it4.
What are the side effects of TB-500?
Unknown in humans. FDA states it lacks important information about safety issues, including whether TB-500 would cause harm if given to humans4.
References
Every source below was retrieved from its official API or page and cached on the data-edition date. Numbers match the margin notes.
- 1 PubMed 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. PMID 23084823; doi:10.1016/j.chroma.2012.09.043.
- 2 PubMed Esposito S, Deventer K, Goeman J, et al. 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.
- 3 PubMed 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.
- 4 FDA Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. U.S. FDA, content current as of 04/22/2026.
- 5 PubMed 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.
- 6 PubChem PubChem compound record: Unii-qhk6Z47gtg. C38H68N10O14 · MW 889 g/mol.
- 7 PubChem PubChem compound record: Timbetasin. C212H350N56O78S · MW 4963 g/mol.
- 8 ClinicalTrials.gov Assessment of the Safety and Efficacy of RGN-259 Ophthalmic Solutions for Dry Eye Syndrome: ARISE-3. ReGenTree, LLC · PHASE3 · completed.
- 9 ClinicalTrials.gov Assessment of the Safety and Efficacy of RGN-259 Ophthalmic Solutions for Dry Eye Syndrome : ARISE-2. ReGenTree, LLC · PHASE3 · completed.
- 10 PubMed Guarnera G, DE Rosa A, Camerini R. Thymosin beta-4 and venous ulcers: clinical remarks on a European prospective, randomized study on safety, tolerability, and enhancement on healing. Ann N Y Acad Sci 2007. PMID 17495250; doi:10.1196/annals.1415.003.
- 11 ClinicalTrials.gov Safety and Efficacy Study of Thymosin Beta 4 in Patients With Acute Myocardial Infarction.Infarction. Beijing Northland Biotech. Co., Ltd. · PHASE2 · completed.
- 12 ClinicalTrials.gov Efficacy and Safety Study of Thymosin Beta 4 in Patients With Acute Myocardial Infarction. Beijing Northland Biotech. Co., Ltd. · PHASE2 · completed.
- 13 ClinicalTrials.gov TB-500 (Thymosin Beta 4 17-23 Fragment) for Cardiovascular Biomarkers in Stable ASCVD. Hudson Biotech · PHASE1/PHASE2 · recruiting.
- 14 ClinicalTrials.gov ClinicalTrials.gov registry search: "thymosin beta 4" OR "thymosin beta-4" OR TB-500 OR RGN-259 OR RGN-137. 20 registered studies at fetch.