TB-500 is a research-market name whose best-characterized published preparation contains Ac-LKKTETQ, an acetylated seven-amino-acid segment of thymosin β4. Interest in it grew from the parent peptide's involvement in cell movement and tissue repair. The fragment's own evidence is concentrated in chemical identification, metabolism and a fibroblast experiment that found activity in one breakdown product. Understanding those experiments explains both the scientific interest and why clinical claims about injury recovery remain unsettled.
Overview
Molecular profile
- Studied form
- N-acetylated thymosin β4 residues 17–23, free base with free carboxyl end Source
- Sequence
- Ac-Leu-Lys-Lys-Thr-Glu-Thr-Gln-OH (Ac-LKKTETQ) Source
- Length
- 7 amino acids Source
- Molecular formula
- C38H68N10O14 (free base) Source
- Molecular weight
- 889.01 g/mol (free base) Source
- CAS number
- 885340-08-9 (free base) Source
Forms and derivatives
TB-500 acetate
Acetate salt of the acetylated fragment. FDA records the monoacetate separately as C38H68N10O14·CH3COOH, 949.1 g/mol; commercial use of the name can obscure the form.
Unacetylated LKKTETQ
The seven-residue internal thymosin β4 sequence with a free amino end. Philp and colleagues tested it in aged-mouse dermal wounds.
Ac-LKKTE and other metabolites
Shorter products generated during Ac-LKKTETQ metabolism. Ac-LKKTE was the only tested material with significant scratch-closure activity in the 2024 fibroblast comparison.
Full-length thymosin β4 and vendor TB-500 usage
The mature parent contains 43 residues. Some sources use TB-500 for a preparation described as synthetic thymosin β4; the 2026 tendon paper gives a supplier code without a sequence/form audit.
The defined molecule reviewed here is N-acetyl-LKKTETQ with a free carboxyl end. Its seven residues correspond to positions 17–23 of mature thymosin β4. The acetyl group attached to the first leucine is part of the identity: it changes the chemistry of the peptide's terminal amino group. FDA's 2026 identity table lists the free-base form as C38H68N10O14 with a molecular weight of 889.01 g/mol and records its acetate salt separately. FDA's TB-500 assessment also describes inconsistent commercial naming, including products bearing different active moieties.
Two independent analytical papers in 2012 provided a firmer basis for this identity. Esposito and colleagues identified the acetylated fragment in a TB-500 preparation, while Ho and colleagues analyzed a veterinary product and developed methods for finding its ingredient after exposure. The name printed on a product therefore carries less chemical information than the sequence, acetylation, salt form and analytical characterization reported in a study. Esposito et al., Ho et al.
Uses and research areas
The published fragment work has two main purposes. Anti-doping laboratories study how to recognize Ac-LKKTETQ and its metabolites in biological samples. Repair researchers ask whether a short sequence derived from thymosin β4 changes cell movement or wound-associated processes. These purposes overlap in metabolism research, because the substance initially introduced into a system may produce shorter peptides with different activity.
The historical wound rationale includes experiments with full-length thymosin β4 and with unacetylated LKKTETQ. Philp and colleagues tested the latter in aged mice and reported improved dermal repair. That preparation supplies a useful comparison within the peptide family. The question for Ac-LKKTETQ is whether its modification, metabolism and tissue exposure preserve the relevant response. Philp et al.
Mechanism of action
Actin is a protein that cells assemble into filaments to support shape and movement. Mature thymosin β4 binds individual actin units and helps regulate their availability. Its LKKTETQ region contributed to the interest in shorter peptides, but contacts elsewhere in the parent also matter. Hannappel and Wartenberg found that full-length thymosin β4 sequestered actin at a one-to-one ratio, whereas two larger fragments, residues 13–43 and 24–43, failed to prevent polymerization in their assay. Their experiment illustrates how activity depends on the whole tested structure; it did not directly compare Ac-LKKTETQ with the parent. Hannappel and Wartenberg
Rahaman and colleagues' 2024 metabolism study included a scratch assay: the investigators created a gap in a layer of cultured fibroblasts, cells that help build connective tissue, and measured how much of the gap closed. Only the breakdown product Ac-LKKTE produced a statistically clear increase in gap closure versus the study's control. The parent Ac-LKKTETQ did not establish that increase under the reported conditions. This raises the possibility that a breakdown product contributes to the response, but testing that explanation in tissue would require measuring both its concentration and the tissue response. Rahaman et al.
Pharmacokinetics
A validated human absorption, distribution or elimination profile for this exact acetylated fragment was not established in the acquired sources, so no concentration-time graph is shown. The available studies demonstrate that enzymes generate several shorter acetylated peptides and that some can remain detectable after exposure.
In Rahaman and colleagues' rat work, Ac-LK had the highest reported metabolite concentration in the initial 0–6-hour urine collection interval, while Ac-LKK remained detectable for up to 72 hours. These are urine-detection observations. They do not specify how long intact Ac-LKKTETQ circulated or how long a target tissue experienced an active concentration. Ho and colleagues' horse work similarly developed sensitive plasma and urine detection; its analytical thresholds describe the method's sensitivity. Rahaman et al., Ho et al.
Research findings
Chemical identification and post-exposure detection
Esposito and colleagues used high-resolution mass spectrometry to identify the acetylated 17–23 fragment in a TB-500 preparation. Their work established a defined analyte for subsequent testing. Ho and colleagues then showed that the parent and metabolites could be identified in samples from exposed horses using chromatographic behavior and characteristic mass-spectral signals. Neither experiment measured tendon strength, muscle recovery or wound closure in the animals. Their contribution is reliable recognition of the studied chemical material. Esposito et al., Ho et al.
The parent fragment and its metabolites
The 2024 study investigated breakdown of Ac-LKKTETQ in human serum and enzyme systems, analyzed urine from treated rats, and tested the parent peptide and selected breakdown products in fibroblast cultures. The human-serum experiment took place in the laboratory; no human participants received TB-500. The tested materials did not show detectable cell toxicity under those culture conditions. Only Ac-LKKTE produced a statistically clear increase in closure of a gap in the cell layer; the parent peptide did not establish the same result. Closing such a gap measures how cultured cells spread across it. Repairing a wound in an animal or person also requires blood supply, immune responses and tissue strong enough to perform its function. Rahaman et al.
What the related wound experiments contribute
Philp and colleagues reported that unacetylated LKKTETQ improved skin-wound repair in aged mice to a degree comparable with full-length thymosin β4. In the full-length experiments in diabetic mice, wounds contracted more and contained more deposited collagen, while movement of keratinocytes, the cells that form the outer skin layer, did not differ. Wound contraction, collagen deposition and skin-cell movement describe different parts of repair. These findings concern the stated preparations and mouse models; they do not establish the same response to acetylated Ac-LKKTETQ. Philp et al.
Human ocular trials discussed on the thymosin β4 profile used full-length trial formulations. For example, a small severe-dry-eye trial studied RGN-259 in nine patients. Those findings concern the ocular formulation and the 43-residue parent; they do not provide a clinical efficacy result for Ac-LKKTETQ. Sosne, Dunn and Kim
A recent tendon study with unresolved preparation identity
Biçer and colleagues' 2026 study cut and surgically repaired the Achilles tendons of 32 rats, then assigned them to a product labelled TB-500, BPC-157, both products or vehicle, the preparation without either peptide. The paper does not report the vehicle's composition. Each of the four groups contained eight animals, with four tendons per group used for each outcome. The preparations were given intraperitoneally, into the abdominal cavity. At day 30, the investigators pulled repaired tendons until they broke and measured the force they withstood. Tendons from the TB-500-labelled group withstood more force than control tendons (adjusted P=0.0406). Those from the BPC-157 group also withstood more force on average, but that difference was too uncertain to establish an effect (adjusted P=0.389). The study did not establish an advantage from the combination or a difference between the two single-product groups. The paper calls its TB-500 material synthetic thymosin β4 and gives a supplier code, but supplies no sequence or independent form characterization. Assignment of this result to Ac-LKKTETQ therefore remains unresolved. Biçer et al.
Safety and tolerability
The exact fragment lacks an adequate clinical safety record in the sources reviewed here. A negative cytotoxicity screen in fibroblasts provides a narrow observation about those cells and conditions. It leaves immune reactions, systemic organ effects, uncommon adverse events and longer exposure unresolved.
FDA's 2026 assessment states that neither the evaluated free base nor acetate is a component of an FDA-approved drug. It identifies risks from uncertain identity, peptide impurities and aggregation, together with limited safety information. For injectable preparations, sterility, endotoxins and particulates are additional material concerns. The briefing document is an agency evaluation prepared for advisory discussion; its recommendation is distinct from a final regulatory determination. FDA assessment
What the research means
The analytical studies identify Ac-LKKTETQ and show why its breakdown products need separate testing. They do not establish that this acetylated fragment helps people recover from injury. A clinical test of that claim would need a chemically verified preparation, measurements of exposure at the relevant tissue, an actual comparison group and an outcome such as movement or strength.
The cell experiment established increased gap closure with Ac-LKKTE compared with the study's control; it did not establish that increase with the parent fragment Ac-LKKTETQ. A next experiment could determine which molecule reaches injured tissue and whether it changes repair there. Chemical detection, cultured-cell behavior and recovery in a person remain different measurements.
FAQs
What does the name TB-500 identify?
The analytical studies on this page identified Ac-LKKTETQ, an acetylated seven-residue peptide. Commercial naming varies, so the sequence, salt form and analytical characterization determine which preparation a result concerns.
Did the fibroblast study find a wound-healing effect from the parent?
In this scratch assay, the investigators created a gap in a layer of fibroblasts and measured how much it closed. Only Ac-LKKTE, one of the tested breakdown products, produced a statistically clear increase in gap closure relative to the study's control. The parent Ac-LKKTETQ did not establish the same increase under the reported conditions. An explanation of wound repair in tissue would also need to show whether an active breakdown product reaches the wound.
Is a metabolite detected after 72 hours evidence of a 72-hour half-life?
The rat paper reported detectable Ac-LKK in urine through 72 hours. Detection depends on the metabolite, collection interval and assay sensitivity. An elimination half-life requires a concentration decline for a specified analyte; that value was not established by the urine-detection statement.
What does the recent tendon experiment add?
The investigators cut and surgically repaired Achilles tendons in rats, then tested how much pulling force the repaired tendons could withstand before breaking. At day 30, the group given the supplier-labelled TB-500 product withstood more force than the group given vehicle, the preparation without peptide. The publication did not report the vehicle's composition or independently establish the product's sequence and chemical form. Its result therefore cannot yet be assigned to the acetylated Ac-LKKTETQ fragment.
Can full-length thymosin eye trials answer the fragment's clinical question?
Those trials studied an ophthalmic formulation of the parent peptide in ocular disease. Ac-LKKTETQ has a different chain and its own metabolism. The clinical outcomes remain attached to the preparation tested.
Comparisons and related reading
References
Identified Ac-LKKTETQ in a veterinary preparation and detected the parent and metabolites in equine urine and plasma after exposure.
Measured fragment metabolism in laboratory systems and rats and compared fibroblast responses; Ac-LKKTE alone improved scratch closure.
An independent analytical characterization established the acetylated fragment in a product named TB-500.
The agency defines the acetylated fragment, differentiates its acetate salt and assesses the evidence and safety issues for compounding.
Full-length thymosin β4 bound actin monomers at a 1:1 ratio; the tested 13–43 and 24–43 fragments did not prevent polymerization.
The rodent experiments tested full-length thymosin β4 and unacetylated LKKTETQ; migration, contraction and collagen results varied with the model.
At day 56 the report described lower discomfort and total corneal staining in treated eyes.
After Achilles-tendon cutting and surgical repair in rats, the investigators measured the force needed to break the repaired tendons. The TB-500-labelled group withstood more force than the no-peptide vehicle group, but the publication does not establish its peptide sequence or chemical form.
Glossary
- Acetylation
- Attachment of an acetyl group to a molecule; for Ac-LKKTETQ it modifies the amino terminus.
- Metabolite
- A chemical product formed when the introduced substance is transformed or broken down.
- Scratch assay
- A culture experiment that measures closure of a gap created in a layer of cells.
- Actin
- A protein assembled into filaments that support cell shape and movement.
- Mass spectrometry
- An analytical technique that helps identify molecules from their mass-related signals and fragmentation patterns.