Educational reference. Research use only.
TB-500: Mechanism, Research, and Regulatory Status
TB-500 is a synthetic seven-residue peptide, Ac-LKKTETQ, the N-terminally acetylated 17-23 fragment of thymosin beta-4, CAS 885340-08-9, molecular weight 889.0 g/mol. No human clinical trials of TB-500 have been published; the biology cited for TB-500 comes largely from preclinical work on full-length thymosin beta-4. TB-500 is supplied for research use only.
Last reviewed 2026-09-29
What is TB-500?
TB-500 key facts
TB-500 is a synthetic peptide with the sequence Ac-Leu-Lys-Lys-Thr-Glu-Thr-Gln (Ac-LKKTETQ), CAS number 885340-08-9, formula C38H68N10O14 and a molecular weight of 889.0 g/mol. Esposito and colleagues characterized the material sold as TB-500 in Drug Testing and Analysis in 2012 as the N-terminally acetylated 17-23 fragment of thymosin beta-4, not the intact 43-residue protein of 4963.4 Da. Full-length thymosin beta-4 is the main G-actin-sequestering peptide in eukaryotic cells, binding actin monomers one-to-one through the actin-binding region that the 17-23 fragment spans. Bock-Marquette and colleagues reported in Nature in 2004 that full-length thymosin beta-4 activated integrin-linked kinase in cardiac cells, and Goldstein reviewed its tissue-repair biology in 2005. Ho and colleagues published LC-MS methods for detecting TB-500 in equine urine and plasma in 2012. Mechanistic work on the fragment itself is much thinner than on the parent protein, and no human trial of TB-500 has been published. TB-500 is not FDA-approved, is prohibited by WADA under S2, and is supplied for research use only.
How does TB-500 work?
The full-length parent protein from which TB-500 is derived is the main peptide inside eukaryotic cells that sequesters G-actin, meaning it holds single actin units in reserve so they are not built into filaments. It binds monomeric G-actin one-to-one through a conserved actin-binding motif. That keeps a cytoplasmic reservoir of actin ready to polymerize and buffers the G-actin/F-actin balance that governs cytoskeletal remodeling and cell movement.
An important identity distinction applies to this compound. Peer-reviewed analytical work has characterized the material supplied as TB-500 as the N-terminal acetylated 17-23 fragment of that protein (Ac-LKKTETQ), not the intact 43-residue form. Essentially all of the biology summarized here was generated with the full-length parent.
Beyond that role inside the cell, the full-length peptide is released outside cells at sites of tissue injury. There it has been reported to influence endothelial cell migration, angiogenic tube formation, and inflammatory signaling. In cardiac tissue, Bock-Marquette and colleagues reported that the parent peptide forms a functional complex with PINCH and integrin-linked kinase, activating ILK and downstream Akt signaling.
The peptide has no fixed shape in free solution and takes on partial helical character when it binds actin, a feature typical of its peptide family. Its small size and lack of stable tertiary structure make it a substrate for exopeptidase processing, which generates shorter fragments including the N-terminal Ac-SDKP tetrapeptide, itself the subject of documented activity in the literature. Mechanistic work on the isolated 17-23 actin-binding fragment is substantially thinner than for the intact 43-mer.
What has research on TB-500 found?
What published peer-reviewed research and preclinical studies have established about TB-500:
- 01The full-length parent protein is described in the literature as the major actin-sequestering molecule in eukaryotic cells (Goldstein 2005).
- 02Bock-Marquette and colleagues reported that the parent peptide forms a complex with PINCH and integrin-linked kinase, resulting in ILK activation in cardiac cells (Nature 2004).
- 03Review literature describes a role for the parent peptide in dermal and corneal wound-healing models (Goldstein 2005; Crockford 2010).
- 04Analytical characterization found the material sold as TB-500 to be the N-terminal acetylated 17-23 fragment of its parent protein, not the intact protein (Esposito 2012).
- 05LC-MS/MS methods for detecting TB-500 in equine urine and plasma have been developed for doping-control purposes (Ho 2012).
- 06UniProt annotates residues 2-5 of the mature chain as the separately bioactive hemoregulatory peptide Ac-SDKP.
Frequently asked questions about TB-500
Is TB-500 the same as its full-length parent protein?+
No, and the distinction matters when reading the literature. The parent is a 43-residue endogenous peptide. Analytical work has characterized the material supplied as TB-500 as the N-terminal acetylated 17-23 fragment (Ac-LKKTETQ), which corresponds to the actin-binding region but lacks the remainder of the sequence, including the separately bioactive N-terminal Ac-SDKP motif. Published findings generated with the full-length parent should not be attributed to the fragment.
What is the proposed mechanism?+
The full-length parent protein acts as the principal intracellular G-actin sequestering peptide, binding monomeric actin 1:1 and buffering the G-actin/F-actin equilibrium that governs cytoskeletal remodeling and cell motility. Additional reported activity includes complex formation with PINCH and integrin-linked kinase in cardiac cells. Mechanistic characterization of the isolated 17-23 fragment is considerably more limited.
Are there human clinical trials of TB-500?+
No. No human clinical trial of TB-500 (Ac-LKKTETQ) has been conducted. Human data that is sometimes cited in this context comes from RGN-259, an ophthalmic solution of the full-length synthetic parent protein studied in dry eye disease. That is a different molecule in a different formulation, and the larger of those Phase 2 studies did not meet its primary endpoints.
How does it differ from thymosin alpha-1?+
They are unrelated peptides that are frequently confused because of the shared thymosin naming. Thymosin alpha-1 is a 28-residue immunomodulatory peptide with an entirely different sequence, mechanism, and research literature. It is not interchangeable with TB-500 or its parent protein in experimental design.
How should it be stored?+
Store lyophilized material at -20C, desiccated and protected from light, and equilibrate to room temperature before opening to prevent condensation on hygroscopic powder. As an unstructured, protease-labile peptide, it should not be subjected to repeated freeze-thaw cycles.
Why do anti-doping authorities test for it?+
TB-500 and the parent protein it derives from fall under WADA Prohibited List section S2 as growth factors, prohibited at all times in and out of competition. Validated LC-MS/MS detection methods have been published for both human and equine testing contexts.
References & sources
Every citation below was resolved against its primary source before publication. Each PMID was checked against its PubMed record and each DOI through doi.org. Follow any link to read the paper at the publisher rather than taking our summary on trust.
- [1]Goldstein AL. Thymosin beta4: actin-sequestering protein moonlights to repair injured tissues. Trends in Molecular Medicine. 2005. PMID: 16099219 DOI: 10.1016/j.molmed.2005.07.004
- [2]Bock-Marquette I, Saxena A, White MD, Dimaio JM, Srivastava D. Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature. 2004. PMID: 15565145 DOI: 10.1038/nature03000
- [3]Crockford D, Turjman N, Allan C, Angel J. Thymosin beta4: structure, function, and biological properties supporting current and future clinical applications. Annals of the New York Academy of Sciences. 2010. PMID: 20536467 DOI: 10.1111/j.1749-6632.2010.05492.x
- [4]Esposito S, Deventer K, Goeman J, Van der Eycken J, Van Eenoo P. 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. 2012. PMID: 22962027 DOI: 10.1002/dta.1402
- [5]Ho ENM, Kwok WH, Lau MY, Wong ASY, Wan TSM, Lam KKH, Schiff PJ, Stewart BD. 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. 2012. PMID: 23084823 DOI: 10.1016/j.chroma.2012.09.043
Where this data comes from
- Citations & trial data: PubMed (NCBI, U.S. National Library of Medicine), Crossref and ClinicalTrials.gov.
- Chemical identity: PubChem and UniProt. Where sources conflicted, the disputed value is omitted rather than guessed.
- Regulatory status: U.S. FDA publications and, where applicable, the WADA Prohibited List. Compounding status changes often, so check FDA directly before relying on it.
- Purity, form and storage are handling and supplier conventions, not literature-derived values. Confirm against the lot-specific certificate of analysis. General handling is covered in the storage and stability guide.
Content last reviewed 2026-09-29. Compiled by Veridian Research from the primary literature. This page is an educational reference for laboratory researchers. It is not medical advice, and it describes no human use.
Is TB-500 approved for human use?
Neither TB-500 nor its full-length parent protein is approved by the FDA for any indication, and no product in this family has completed a successful Phase 3 program. TB-500 and the parent it derives from fall under WADA Prohibited List section S2 (Peptide Hormones, Growth Factors, Related Substances and Mimetics), prohibited at all times both in and out of competition. Compounding status under the FDA 503A bulk drug substances framework has been subject to ongoing review and change; verify against FDA's currently published list rather than any secondary source. Supplied strictly as a research chemical for in vitro and laboratory research use only. It is not for human or veterinary use, and not for diagnostic or therapeutic use.
Research-use-only material
Specifications and certificate of analysis
TB-500 is stocked as a research reagent. Analytical documentation, covering identity, purity and the lot-specific certificate of analysis, is published in the certificate library.