What is TB-500?
TB-500 is a synthetic acetylated peptide (Ac-LKKTETQ) modeled after the active site of thymosin β4 (Tβ4), a protein known for its actin-binding and tissue repair functions. Although TB-500 is structurally related to Tβ4, its biological activity has not been conclusively demonstrated. Recent studies have focused on its metabolic fate and analytical detection, rather than direct functional outcomes (Rahaman et al. 2024).
Researchers quantified TB-500 and six metabolites in vitro and in rat urine. Four primary metabolites—Ac-LKKTE, Ac-LKK, Ac-LK, and Ac-L—were confirmed with authentic standards. Ac-LK was the most abundant early metabolite (0–6 h), while Ac-LKK persisted up to 72 h. Among these, only Ac-LKKTE showed significant in-vitro wound healing activity, suggesting that prior reports of TB-500’s biological effects may actually be attributable to this metabolite (Rahaman et al. 2024).
Separately, studies on the parent compound Tβ4 demonstrated enhanced axonal remodeling, oligodendrogenesis, and vessel density in a rat stroke model, despite no change in infarct volume. This suggests a mechanism of structural recovery rather than neuroprotection (Morris et al. 2010).
References
Morris, D. C., Chopp, M., Zhang, L., Lu, M., & Zhang, Z. G. (2010). Thymosin β4 improves functional neurological outcome in a rat model of embolic stroke. Neuroscience, 169(2), 674– 682. https://doi.org/10.1016/j.neuroscience.2010.05.017
Rahaman, K. A., Muresan, A. R., Min, H., Son, J., Han, H.-S., Kang, M.-J., & Kwon, O.-S. (2024). 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. Journal of Chromatography B, 1235, 124033. https://doi.org/10.1016/j.jchromb.2024.124033