What Is TB-500?
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Overview TB-500 (also known as Fequesetide) is a synthetic heptapeptide corresponding to the N-acetylated amino acid sequence 17–23 of the naturally occurring protein Thymosin Beta-4 (Tβ4). Its sequence is Ac-LKKTETQ.[1][2] The parent molecule, Thymosin Beta-4, is a ubiquitous 43-amino acid polypept...
Overview
TB-500 (also known as Fequesetide) is a synthetic heptapeptide corresponding to the N-acetylated amino acid sequence 17–23 of the naturally occurring protein Thymosin Beta-4 (Tβ4). Its sequence is Ac-LKKTETQ.[1][2]
The parent molecule, Thymosin Beta-4, is a ubiquitous 43-amino acid polypeptide originally isolated from the thymus gland. It is found in high concentrations in blood platelets, white blood cells, and wound fluid, and belongs to the β-thymosin family of actin-sequestering proteins.[3]
TB-500 was developed based on the discovery that the specific seven-amino acid sequence (17–23) within Tβ4 is responsible for its actin-binding properties, which are critical for cell migration and tissue repair. The shorter fragment retains the essential angiogenic and wound-healing activities of the parent molecule while being more economical to synthesize.[6][8]
The U.S. FDA has classified TB-500 as a Category 2 Bulk Drug Substance, citing insufficient safety-related information and immunogenicity risk. It is prohibited from being compounded by outsourcing facilities.[4] TB-500 and Tβ4 are also explicitly prohibited by WADA under Section S2.3 at all times.[5]
Discovery and design rationale
TB-500 emerged from a structural decomposition of full-length Tbeta4 aimed at isolating the minimum sequence required for actin sequestration. The 17–23 LKKTETQ window contains the actin-binding helix identified by NMR and X-ray crystallography of Tbeta4-actin complexes, while the N-terminal Ac-SDKP fragment (residues 1–4) carries the parent's distinct anti-fibrotic and hematopoietic-quiescence activity.[6][7] N-terminal acetylation in TB-500 was retained to mirror the natural Tbeta4 acetylation state and to confer modest exopeptidase resistance.[2]
Research framework
Within the actin-cytoskeleton-modulating peptide research domain, TB-500 is most often referenced alongside Thymosin alpha-1 for parallel thymic-peptide pharmacology, BPC-157 for shared cytoprotection and tissue-repair signaling, and GHK-Cu for matrix-remodeling crosstalk. The compound is supplied here strictly as a research reference standard for in vitro and animal-model investigation, and is not intended for human or veterinary use.
“Preclinical Research Summary Animal Studies (TB-500 Fragment Specifically) StudyModelKey FindingsRef Rahaman et al.”
References
- 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. Drug Testing and Analysis. 2012;4(9):733-738.
- Delcourt V, Garcia P, Chabot B, Bailly-Chouriberry L. TB500/TB1000 and SGF1000: A scientific approach for a better understanding of misbranded and adulterated drugs. Drug Testing and Analysis. 2023;15(4):458-464.
- Goldstein AL, Hannappel E, Sosne G, Kleinman HK. Thymosin β4: a multi-functional regenerative peptide. Expert Opinion on Biological Therapy. 2012;12(1):37-51.
- U.S. Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. FDA.gov. Updated July 8, 2025.
- World Anti-Doping Agency. The 2025 Prohibited List. WADA. January 1, 2025.
- Xing Y, Ye Y, Zuo H, Li Y. Progress on the Function and Application of Thymosin β4. Frontiers in Endocrinology. 2021;12:767785.
- Bock-Marquette I, Maar K, Maar S, et al. International Immunopharmacology. 2023;116:109741.
- Philp D, Badamchian M, Scheremeta B, Nguyen M, Goldstein AL, Kleinman HK. Thymosin β4 and a synthetic peptide containing its actin-binding domain promote dermal wound repair in db/db diabetic mice and in aged mice. Wound Repair and Regeneration. 2003;11(1):19-24.
- Belsky JB, Rivers EP, Filbin MR, Lee PJ, Morris DC. Thymosin beta 4 regulation of actin in sepsis. Expert Opinion on Biological Therapy. 2018;18(sup1):193-197.
- Hinkel R, El-Aouni C, Olson T, et al. Thymosin beta4 is an essential paracrine factor of embryonic endothelial progenitor cell-mediated cardioprotection. Circulation. 2008;117(17):2232-2240.
- 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;432(7016):466-472.
- Smart N, Risebro CA, Melville AA, et al. Nature. 2007;445(7124):177-182.
- Sosne G, Kleinman HK. Investigative Ophthalmology & Visual Science. 2015;56(9):5110-5117.
- Reyes-Gordillo K, Shah R, Popratiloff A, et al. Thymosin-β4 (Tβ4) Blunts PDGF-Dependent Phosphorylation and Binding of AKT to Actin in Hepatic Stellate Cells. American Journal of Pathology. 2011;178(5):2100-2108.
- Malinda KM, Sidhu GS, Mani H, et al. Thymosin beta 4 accelerates wound healing. Journal of Investigative Dermatology. 1999;113(3):364-368.
- Shah R, Reyes-Gordillo K, Cheng Y, et al. Oxidative Medicine and Cellular Longevity. 2018;2018:9630175.
- Rahaman KA, Muresan AR, Min H, et al. Simultaneous quantification of TB-500 and its metabolites by UHPLC-Q-Exactive orbitrap MS/MS and their screening by wound healing activities in-vitro. Journal of Chromatography B. 2024;1235:124033.
- Malinda KM, Sidhu GS, Mani H, et al. Thymosin beta 4 accelerates wound healing. Journal of Investigative Dermatology. 1999;113(3):364-368.
- Sosne G, Ousler GW. Clinical Ophthalmology. 2015;9:877-884.
- Sosne G, Dunn SP, Kim C. Cornea. 2015;34(5):491-496.
- Bao W, Ballard VL, Needle S, et al. Frontiers in Pharmacology. 2013;4:149.
- Treadwell T, Kleinman HK, Crockford D, et al. Annals of the New York Academy of Sciences. 2012;1270:37-44.
- Nguyen J, Verma S, Vuong VT, et al. Engineered Tandem Thymosin Peptide Promotes Corneal Wound Healing. Investigative Ophthalmology & Visual Science. 2025;66(14):31.
- Sosne G, Qiu P, Goldstein AL, Wheater M. Biological activities of thymosin beta 4 defined by active sites in short peptide sequences. The FASEB Journal. 2010;24(7):2144-2151.
- Ho EN, Kwok WH, Lau MY, et al. Doping control analysis of TB-500 in equine urine and plasma by liquid chromatography-mass spectrometry. Journal of Chromatography A. 2012;1265:57-69.
- Kwok WH, Ho ENM, Lau MY, Leung GNW, et al. Doping control analysis of seven bioactive peptides in horse plasma by liquid chromatography-mass spectrometry. Analytical and Bioanalytical Chemistry. 2013;405(8):2595-2606.
- Smart N, Risebro CA, Melville AA, et al. Nature. 2007;445(7124):177-182.
- RegeneRx Biopharmaceuticals. 2009.
- Treadwell T, Kleinman HK, Crockford D, et al. The regenerative peptide thymosin β4 accelerates dermal healing. Annals of the New York Academy of Sciences. 2012;1270:37-44.
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