TB-500 (Thymosin Beta-4 Fragment)

TB-500 is the trade name for Ac-LKKTETQ, a synthetic seven-residue peptide with an acetylated N-terminus corresponding to residues 17 to 23 of the 43-amino-acid human protein thymosin beta-4, supplied here as a laboratory reference material and not approved as a drug for any indication.

This material is for in vitro and laboratory research only. It is not for human or animal consumption, and nothing here describes a use in people or animals. See the research use policy.

One product name, two different molecules

A common documentation error in this category is treating TB-500 and thymosin beta-4 as synonyms. They are not the same substance, a point FDA made directly in its July 2026 briefing document on TB-500-related bulk drug substances, noting that vendor material often uses the two terms interchangeably. Ac-LKKTETQ is a heptapeptide near 889 g/mol; full-length thymosin beta-4 is a 43-residue protein near 4963 g/mol, over five times the mass. Material sold under either name may be either molecule, and a mass spectrum settles it in one measurement. Esposito et al. (2012) did exactly that, identifying Ac-LKKTETQ in a commercial TB-500 formulation by high-performance liquid chromatography with high-resolution mass spectrometry, and separately synthesising the heptapeptide by solid-phase peptide synthesis as a reference standard.

Material made by solid-phase synthesis ships as a salt, usually acetate or trifluoroacetate, so gross vial weight exceeds the peptide weight inside. The acetate salt of the heptapeptide is near 949 g/mol against 889 g/mol for the free base. Net peptide content belongs on the certificate of analysis; our peptide calculator works from that figure, not label weight.

Research history

Thymosin beta-4 was first isolated from thymic tissue fractions and later recognised as a member of the beta-thymosin family, small acidic peptides present at high intracellular concentrations across vertebrate cell types. Goldstein, Hannappel and Kleinman (2005) summarised the shift that defines this literature: a protein characterised as an intracellular regulator of the actin cytoskeleton was later studied for signalling roles outside the cell after injury.

Attention narrowed to the LKKTETQ motif because it is the actin-binding site. Philp et al. (2003), comparing the intact protein against proteolytic fragments and synthetic peptides in human endothelial migration assays and chick aortic arch sprouting assays, reported that peptides lacking any part of the seven-residue actin motif were inactive in those systems. Sosne et al. (2010), working in vitro, extended the mapping, reporting that several biological activities attributed to the intact protein could be assigned to short peptide sequences within it. The preparation named TB-500 emerged from this line of work, initially in a veterinary context: Ho et al. (2012) developed a liquid chromatography-mass spectrometry method to detect N-acetylated LKKTETQ and its metabolites in equine urine and plasma for doping control, one of the few published accounts of what the preparation contains and how it is identified.

Mechanism as described in published work

The intracellular mechanism is well characterised. Thymosin beta-4 binds monomeric G-actin in an approximately one-to-one complex, sequestering it and thereby regulating the pool available for filament assembly. This influences cytoskeletal remodelling and cell shape. The LKKTETQ segment is the portion of the sequence responsible for that interaction.

The extracellular picture is far less settled. No consensus cell-surface receptor for either molecule has been established, and the pathways described in the injury literature are inferred from downstream readouts rather than from a defined binding partner. Bock-Marquette et al. (2004) reported in murine cardiac models that thymosin beta-4 activated integrin-linked kinase and Akt signalling and increased cardiac cell migration and survival. Smart et al. (2007) reported mobilisation of adult epicardial progenitor cells and neovascularisation in a mouse model. Both are preclinical, both used the full-length protein rather than the heptapeptide, and neither identified a receptor.

Study models at a glance

The most recent of these, Bicer et al. (2026), is a preclinical rat study; its authors describe it as exploratory and preliminary and call for dose-optimisation and longer-term work. It does not bear on humans.

Human data

No controlled human trial of Ac-LKKTETQ has been published, for any indication. The heptapeptide has no human efficacy dataset and no human safety dataset. FDA reached the same conclusion in its July 2026 review, stating that it had not identified human data for drug products containing these substances by any route of administration.

The human record for the full-length protein is limited but not empty. Ruff et al. (2010) reported a randomised, placebo-controlled single-dose and multiple-dose study of intravenous thymosin beta-4 in healthy volunteers, a Phase 1 design whose endpoints were adverse events, tolerability and pharmacokinetics rather than clinical outcome. It examined the 43-residue protein, and its findings do not transfer to the heptapeptide. Marketing material that cites thymosin beta-4 clinical work in support of a TB-500 product is citing a different molecule.

Regulatory status

Neither Ac-LKKTETQ nor thymosin beta-4 is approved by the FDA for any indication.

• FDA's published list of bulk drug substances that may present significant safety risks records thymosin beta-4 fragment (LKKTETQ), also known as TB-500, among substances previously in category 2 of the section 503A and 503B interim policies whose nominations were later withdrawn by the nominators. The published safety rationale cites potential immunogenicity for certain routes of administration, the potential for aggregation and peptide-related impurities, and the absence of any human exposure data identified by the agency. FDA's listing carries no date of addition for this substance, and we have seen none published.
• TB-500 (free base) and TB-500 acetate were the subject of an FDA briefing document prepared for the Pharmacy Compounding Advisory Committee meeting of 23-24 July 2026. FDA staff concluded in that document that a balancing of the statutory criteria weighed against placing either substance on the 503A bulks list.
• TB-500 is not on the 503A bulks list. Advisory committee recommendations are non-binding, addition would require notice-and-comment rulemaking, and at the time of writing FDA had published no minutes or voting record for the July 2026 meeting. Reports of the committee's vote circulating elsewhere should be treated as unverified.
• The World Anti-Doping Agency prohibits TB-500; FDA's briefing document places it under section S2.3 of the WADA Prohibited List, the growth factors and growth factor modulators class, which is prohibited at all times. Validated detection methods for the peptide and its metabolites have been published since 2012.

Handling, storage and lot verification

Lyophilised material is hygroscopic and degrades faster in solution than dry. Keep vials sealed and desiccated at -20 C or colder and let them warm to room temperature before opening, so moisture does not condense onto cold powder. Further detail is in our notes on peptide storage and on preparing solutions from lyophilised material.

Because two molecules circulate under one name, mass spectrometric identity confirmation is the line on a certificate that distinguishes them. A lot should also carry HPLC purity with the chromatogram attached, net peptide content, counter-ion identity and water content. Reports for our lots are published under lab testing.

How should TB-500 be stored?

Sealed, desiccated, protected from light, at -20 C or colder. Solutions should be held at 2-8 C and treated as short-lived. Repeated freeze-thaw cycling is a common avoidable cause of purity loss.

How can a buyer tell whether a vial contains the heptapeptide or the full-length protein?

By the observed mass on the certificate of analysis. Ac-LKKTETQ has a molecular weight near 889 g/mol; thymosin beta-4 is near 4963 g/mol. Those two figures cannot be confused. If a certificate reports no mass at all, it has not answered the question that matters most for this compound.

Why do suppliers list different molecular weights for TB-500?

Some catalogue entries carry transcription errors; others describe the full-length protein under the fragment's name, and others quote the acetate salt rather than the free base. PubChem CID 62707662 gives C38H68N10O14 and 889.0 g/mol for CAS 885340-08-9. Any figure materially different from that describes a different substance or a salt form, and should be reconciled against the lot's own mass spectrum rather than against a catalogue.

What is the regulatory status of TB-500?

It is not an approved drug. It is distributed as a research chemical for laboratory use only and is prohibited in sport under the WADA Prohibited List. As of August 2026 it is not on the 503A bulks list and is not eligible for pharmacy compounding on that basis.

References

• Goldstein AL, Hannappel E, Kleinman HK (2005). Thymosin beta4: actin-sequestering protein moonlights to repair injured tissues. Trends in Molecular Medicine.
• Philp D, Huff T, Gho YS, Hannappel E, Kleinman HK (2003). The actin binding site on thymosin beta4 promotes angiogenesis. FASEB Journal.
• Bock-Marquette I, Saxena A, White MD, DiMaio JM, Srivastava D (2004). Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature.
• Smart N, Risebro CA, Melville AA, Moses K, Schwartz RJ, Chien KR, Riley PR (2007). Thymosin beta4 induces adult epicardial progenitor mobilization and neovascularization. Nature.
• Sosne G, Qiu P, Goldstein AL, Wheater M (2010). Biological activities of thymosin beta4 defined by active sites in short peptide sequences. FASEB Journal.
• Ruff D, Crockford D, Girardi G, Zhang Y (2010). A randomized, placebo-controlled, single and multiple dose study of intravenous thymosin beta4 in healthy volunteers. Annals of the New York Academy of Sciences.
• Esposito S, Deventer K, Goeman J, Van der Eycken J, Van Eenoo P (2012). 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 Testing and Analysis.
• Ho EN, Kwok WH, Lau MY, Wong AS, Wan TS, Lam KK (2012). Doping control analysis of TB-500, a synthetic version of an active region of thymosin beta4, in equine urine and plasma by liquid chromatography-mass spectrometry. Journal of Chromatography A.
• Bicer O, Adanir O, Guleryuz Y, Balci EC, Dincel YM, Yenigun MY, Aydin C, Bayrak BY (2026). Effects of BPC-157 and TB-500 on Achilles tendon healing in rats: A histopathological and biomechanical study. Joint Diseases and Related Surgery.