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TB-500 (Thymosin Beta-4 Fragment) — clinical & mechanistic profile
TB-500 is a synthetic 7-amino-acid fragment from thymosin beta-4's actin-binding site. A Phase 1/2 trial launched February 2026 investigates its cardiovascular effects in adults with stable atherosclerotic disease. Phase 1 safety data in 84 healthy volunteers showed favorable tolerability. 2025 research reveals its wound-healing activity may stem from the metabolite Ac-LKKTE rather than the parent compound.
Research status
clinical investigational
Sequence
Ac-LKKTETQ (active fragment of 43-aa Tβ4)
Molecular weight
4963 Da (full Tβ4) / ~900 Da (TB-500 fragment)
Molecular formula
C212H350N56O78S (full Tβ4)
Studied applications
- •G-actin sequestration: forms 1:1 complex with G-actin, preventing F-actin assembly, modulating cytoskeletal dynamics for cell migration
- •ROCK1 downregulation: decreases ROCK1 protein levels particularly under hypoxia, reducing profibrotic signaling via MRTFA/SRF pathways
- •Wound healing: Phase 2 trials show 42% improvement in reepithelialization by day 4, 61% by day 7; thicker collagen, reduced scarring
- •Cardiac protection: post-MI trials with EPC transplantation showed improved walk time and cardiac function at 6 months; activates epicardial progenitors
- •Progenitor mobilization: enhances stem cell recruitment and differentiation; reactivates embryonic gene programs in cardiac tissue
Mechanisms of action
- •G-actin sequestration: binds G-actin 1:1, inhibits F-actin polymerization, modulates actin structures in hypoxic cardiac cells
- •ROCK1/MRTFA pathway: decreases ROCK1 protein, reduces profibrotic signaling via MRTFA/SRF in cardiac cells under hypoxia
- •Cell migration promotion: alters cytoskeletal dynamics to enhance fibroblast, stem cell, and progenitor movement to injury sites
- •Angiogenesis induction: promotes new vessel formation via endothelial proliferation; increases capillary density and capsulin+ progenitors
- •Anti-inflammatory/anti-fibrotic: reduces myofibroblast accumulation, modulates inflammatory markers, decreases scarring potential
- •Epicardial activation: reactivates embryonic gene programs, epicardial thickening, Wnt pathway modulation in cardiac models
- •Not approved by FDA or any regulatory agency for human therapeutic use
- •Prohibited by WADA under S0 category (Non-Approved Substances) for athletic use
- •Human clinical data limited to Phase 2 trials for specific wound types
- •Most evidence derives from animal models rather than human subjects
- •Long-term safety data in humans is not established
Peer-reviewed references
- Goldstein AL, et al. — Thymosin beta-4 in wound repair (2008)PMID: 18492738View
- Bock-Marquette I, et al. — Cardiac repair mechanismsPMID: 22431019View
- Phase 2 clinical trial results for pressure/stasis ulcersPMID: 23050815View
- Sosne G, et al. — TB4 in corneal wound healingPMID: 16923388View
- Smart N, et al. — Cardiac progenitor cell activationPMID: 17641392View
For research use only. This summary is a research-scientific overview compiled from peer-reviewed sources. It is not medical advice and is not intended for human or veterinary consumption.
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