DRPSHP

Scientific Reference

TB-500

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

Residues 17 to 23 of thymosin beta-4, a 43-residue protein that binds actin, are reproduced by TB-500 as the seven-residue chain Ac-LKKTETQ. The copied stretch lies in the middle of the parent's actin-binding region. Since that position is internal in the real protein, the acetyl cap at the front end is an addition made in synthesis. Care is needed with the name, because it is sometimes attached to full-length thymosin beta-4 even though the two differ in size (roughly 0.9 kDa against 5 kDa) and in the portions of the protein they contain. The bulk of the literature is on the whole protein, in cell culture and rodent models of skin, heart and corneal injury, whereas studies of the fragment by itself are far fewer and cannot be taken to show the same behaviour.

Mechanism of Action

In its complete form thymosin beta-4 attaches to a single monomeric G-actin molecule, forming a one-to-one complex, and is one of the main actin-sequestering proteins in many cells, keeping actin from polymerising. Structure studies place the LKKTET motif, a feature of the WH2 family of actin-binding domains, at the heart of the interaction, with segments toward both ends of the protein also touching actin. A small number of cell experiments say the isolated fragment alters how endothelial cells migrate, though how well it matches the whole protein's actin binding is uncertain. Different properties credited to thymosin beta-4 derive from other regions: the N-terminal tetrapeptide Ac-SDKP, for example, is liberated by enzymatic cleavage and has its own literature.

Molecular Information

  • Type: Heptapeptide (thymosin beta-4 fragment)

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