# TB-500

- Canonical: https://residue.info/c/tb-500/
- Also called: Thymosin beta-4 fragment (LKKTETQ), Ac-LKKTETQ, Thymosin β4 (parent protein), Timbetasin
- Evidence grade: D (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.
- Status: Not FDA-approved · FDA compounding nomination withdrawn
- PubChem CID: 62707662
- Updated: 2026-10-19 · Reviewed by: Residue Editorial Team

TB-500 is acetylated LKKTETQ, residues 17–23 of the protein thymosin β4, a region linked to actin binding and wound healing [1][2]. Full-length thymosin β4 has been tested in human trials, mostly as eye drops for dry eye [3], but FDA states it has found no human exposure data for the fragment, which is not FDA-approved [4].

## 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]. (anchor: https://residue.info/c/tb-500/#kf-pmid-22962027)
- The 17–23 segment is described as the active site within thymosin β4 for actin binding, cell migration and wound healing [1]. (anchor: https://residue.info/c/tb-500/#kf-pmid-23084823)
- 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 improved [3]. (anchor: https://residue.info/c/tb-500/#kf-pmid-26056426)
- Thymosin β4 eye drops progressed to phase 3 trials for dry eye and neurotrophic keratopathy [5]. (anchor: https://residue.info/c/tb-500/#kf-pmid-30063853)
- FDA says it has not identified any human exposure data for products containing the LKKTETQ fragment and lacks important safety information [4]. (anchor: https://residue.info/c/tb-500/#kf-fda-cat2)

## Effects by system
- Eye (full-length Tβ4) (grade B): Phase 2: primary endpoints not met; secondary improvements in discomfort and corneal staining [3]. (anchor: https://residue.info/c/tb-500/#effect-eye-full-length-t-4)
- Skin ulcers (full-length Tβ4) (grade C): A randomized, dose-escalation trial of topical Tβ4 in venous ulcers was designed and enrolling in 2007 [6]. (anchor: https://residue.info/c/tb-500/#effect-skin-ulcers-full-length-t-4)
- Any effect of TB-500 fragment (grade D): No human exposure data identified by FDA [4]; human detection studies are for anti-doping only [2][1]. (anchor: https://residue.info/c/tb-500/#effect-any-effect-of-tb-500-fragment)

## 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 healing [1]. TB-500 emerged as a veterinary preparation; its key ingredient is that seven-residue segment with an artificial acetyl group on the N-terminus [1]. Analysis of a TB-500 product by high-resolution mass spectrometry confirmed Ac-LKKTETQ as its content [2].

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 profile [7][8].

## 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 observed [3]. A 2018 review described phase 3 trials for dry eye and neurotrophic keratopathy as ongoing [5]; ClinicalTrials.gov lists several completed phase 3 studies of the eye-drop formulation, RGN-259 [9][10].

**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 days [6].

**Heart.** Thymosin β4 has been studied in acute myocardial infarction in completed phase 2 trials registered by Beijing Northland Biotech [11][12].

## 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 urine [2] and in equine urine and plasma, where its metabolites were mapped [1]. A recruiting phase 1/2 study lists the 17–23 fragment for cardiovascular biomarkers [13].

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 humans [4].

## 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 appear [14].

## Frequently asked questions
**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 protein [2][1]. Human trials of thymosin β4 used the full protein [3].

**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 it [4].

**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 humans [4].

**Why is TB-500 tested for in sport?**
Anti-doping laboratories developed methods to detect TB-500 and its metabolites because it was suspected of being used as a doping agent in human and equine sport [2][1].

**Are there clinical trials of TB-500?**
Most registered studies test full-length thymosin β4 [14]. One recruiting study registers the 17–23 fragment itself for cardiovascular biomarkers [13].


## Sources
[1] 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. Ho EN et al. J Chromatogr A. 2012. https://pubmed.ncbi.nlm.nih.gov/23084823/
[2] 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. Esposito S et al. Drug Test Anal. 2012. https://pubmed.ncbi.nlm.nih.gov/22962027/
[3] Thymosin 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. https://pubmed.ncbi.nlm.nih.gov/26056426/
[4] Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. U.S. FDA, content current as of 04/22/2026. https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks
[5] Thymosin beta 4 and the eye: the journey from bench to bedside. Sosne G Expert Opin Biol Ther. 2018. https://pubmed.ncbi.nlm.nih.gov/30063853/
[6] Thymosin 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. https://pubmed.ncbi.nlm.nih.gov/17495250/
[7] PubChem compound record: Unii-qhk6Z47gtg. C38H68N10O14 · MW 889 g/mol. https://pubchem.ncbi.nlm.nih.gov/compound/62707662
[8] PubChem compound record: Timbetasin. C212H350N56O78S · MW 4963 g/mol. https://pubchem.ncbi.nlm.nih.gov/compound/16132341
[9] Assessment of the Safety and Efficacy of RGN-259 Ophthalmic Solutions for Dry Eye Syndrome: ARISE-3. ReGenTree, LLC · PHASE3 · completed. https://clinicaltrials.gov/study/NCT03937882
[10] Assessment of the Safety and Efficacy of RGN-259 Ophthalmic Solutions for Dry Eye Syndrome : ARISE-2. ReGenTree, LLC · PHASE3 · completed. https://clinicaltrials.gov/study/NCT02974907
[11] Safety and Efficacy Study of Thymosin Beta 4 in Patients With Acute Myocardial Infarction.Infarction. Beijing Northland Biotech. Co., Ltd. · PHASE2 · completed. https://clinicaltrials.gov/study/NCT05485818
[12] Efficacy and Safety Study of Thymosin Beta 4 in Patients With Acute Myocardial Infarction. Beijing Northland Biotech. Co., Ltd. · PHASE2 · completed. https://clinicaltrials.gov/study/NCT05984134
[13] TB-500 (Thymosin Beta 4 17-23 Fragment) for Cardiovascular Biomarkers in Stable ASCVD. Hudson Biotech · PHASE1/PHASE2 · recruiting. https://clinicaltrials.gov/study/NCT07487363
[14] 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. https://clinicaltrials.gov/search?intr=%22thymosin%20beta%204%22%20OR%20%22thymosin%20beta-4%22%20OR%20TB-500%20OR%20RGN-259%20OR%20RGN-137

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