Scientific Reference

TB-500

Evidence profile: Human trials studied full-length thymosin beta-4, not the TB-500 fragment

TB-500 is a synthetic seven-residue peptide, Ac-LKKTETQ, matching residues 17 to 23 of the 43-residue actin-binding protein thymosin β4. The stretch it copies lies in the central actin-binding region of thymosin β4; the N-terminal acetyl cap is a synthetic addition, since that position is internal in the native protein. The name is sometimes applied loosely to full-length thymosin β4, and the two should be kept apart: they differ in length, in mass (about 0.9 kDa against about 5 kDa) and in which parts of the parent protein they contain. Most published research concerns the full-length protein, examined in cell culture and in rodent models of skin, cardiac and corneal injury. Work on the fragment alone is far thinner, and it cannot be assumed to share the properties described for the whole protein.

Mechanism of Action

Full-length thymosin β4 binds monomeric G-actin in a one-to-one complex and is a major actin-sequestering protein in many cell types, holding actin in unpolymerised form. Structural studies place the LKKTET motif, shared with the WH2 family of actin-binding domains, at the centre of that contact, flanked by N-terminal and C-terminal segments that also touch actin. A small number of cell studies have reported that the isolated fragment affects endothelial cell migration, but how closely it reproduces the actin binding of the whole protein is not well established. Other activities attributed to thymosin β4 map elsewhere: the N-terminal tetrapeptide Ac-SDKP is released by enzymatic cleavage and has been studied separately.

Molecular Information

  • Type: Heptapeptide (thymosin β4 fragment)
  • Length: 7 amino acids
  • Molecular weight: 889.0 g/mol
  • Molecular formula: C38H68N10O14
  • CAS: 885340-08-9

Published Research

  • Thymosin beta 4: A potential novel adjunct treatment for bacterial keratitis

    Sosne G et al. · International immunopharmacology · 2023 · Clinical

    PMID 37018981 — View on PubMed
  • RGN-259 neurotrophic keratopathy phase III

    0.1% RGN-259 (Thymosin ß4) Ophthalmic Solution Promotes Healing and Improves Comfort in Neurotrophic Keratopathy Patients in a Randomized, Placebo-Controlled, Double-Masked Phase III Clinical Trial

    Sosne G et al. · International journal of molecular sciences · 2022 · Clinical

    PMID 36613994 — View on PubMed
  • The effect of thymosin treatment of venous ulcers

    Guarnera G et al. · Annals of the New York Academy of Sciences · 2010 · Clinical

    PMID 20536470 — View on PubMed
  • A randomized, placebo-controlled, single and multiple dose study of intravenous thymosin beta4 in healthy volunteers

    Ruff D et al. · Annals of the New York Academy of Sciences · 2010 · Clinical

    PMID 20536472 — View on PubMed
  • Simultaneous quantification of TB-500 and its metabolites in in-vitro experiments and rats by UHPLC-Q-Exactive orbitrap MS/MS and their screening by wound healing activities in-vitro

    Rahaman KA et al. · Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2024 · Preclinical

    PMID 38382158 — View on PubMed
  • 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 testing and analysis · 2012 · Preclinical

    PMID 22962027 — View on PubMed