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Synthetic peptide fragment (Ac-LKKTETQ) corresponding to the actin-binding region of thymosin beta-4; note it is NOT the same molecule as full-length recombinant thymosin beta-4

TB-500

Prohibitedaka Thymosin beta-4 fragment, Tbeta4 fragment, TB4 fragment, LKKTETQ peptide

TB-500 is a short synthetic peptide based on the actin-binding portion of thymosin beta-4. Preclinical studies suggest roles in wound healing, angiogenesis and reduced fibrosis, but robust human trials exist only for full-length thymosin beta-4 (RGN-259), a distinct molecule.

Mechanism

The LKKTETQ sequence binds and sequesters actin, influencing cell migration, angiogenesis and tissue remodeling, with reported anti-inflammatory effects and stem/progenitor cell recruitment. Nearly all data derive from full-length thymosin beta-4 or animal models; the mechanism and pharmacology of the TB-500 fragment in humans are not well characterised.

Regulatory Status by Region

  • United States (FDA)Not FDA-approved; TB-500 placed on the 503A Category 2 list (barred from compounding). Full-length thymosin beta-4 (RGN-259) is a separate investigational drug in Phase 3 ophthalmic trials.
  • Australia (TGA)No registered/approved product; an unapproved therapeutic substance.
  • European Union (EMA)No EMA marketing authorisation.
  • WADAProhibited at all times under S2 (peptide hormones, growth factors and mimetics) since 2011.

Key Studies

  • Thymosin beta 4 significantly improves signs and symptoms of severe dry eye in a phase 2 randomized trial (Sosne et al., Sci Rep / Cornea 2015; PMID 25826322 (full-length thymosin beta-4, RGN-259))
  • 0.1% RGN-259 (Thymosin beta-4) Ophthalmic Solution Promotes Healing in Neurotrophic Keratopathy: A Randomized, Placebo-Controlled, Double-Masked Phase III Clinical Trial (PMCID PMC9820614 (full-length thymosin beta-4))
  • TB-500: Status, Risks, and Bans in Sport and Military (WADA S2 classification) (BSCG regulatory summary; WADA Prohibited List S2)

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