◆ Recovery · Actin-Binding Peptide · Tissue Repair
TB-500 (Thymosin Beta-4 Fragment): Mechanism & Research Data
A verified research summary of TB-500 — the synthetic Ac-LKKTETQ heptapeptide fragment of Thymosin Beta-4 — and why it must not be confused with the full-length parent protein.
Silverback Research Team
Independent Literature Review
Compound Data
✓ Research Grade| Compound Name | TB-500 (Thymosin Beta-4 fragment, residues 17–23) |
| Development Codes | Ac-LKKTETQ, Heptapeptide 17-23, Fequesetide |
| CAS Number | 885340-08-9 (fragment) — NOT 77591-33-4 |
| Molecular Weight | 889.02 g/mol (anhydrous free base) |
| Molecular Formula | C38H68N10O14 |
| Sequence | Ac-LKKTETQ (Ac-Leu-Lys-Lys-Thr-Glu-Thr-Gln) |
| Receptor Targets | Intracellular monomeric G-actin (sequestration, Kd ~0.5–0.7 µM) |
| Elimination Half-life | ~7 hours (estimated in vitro) |
| Form (Silverback) | Lyophilised powder |
| Purity (Silverback) | ≥99% by HPLC |
| Storage | −20°C sealed · 2–8°C post-reconstitution |
| Regulatory Status | Investigational — unapproved · AU Schedule 4 · WADA-prohibited |
Research use only. All information is sourced from published literature for informational purposes. Silverback Peptides products are strictly for laboratory research. Not for human consumption, therapeutic use, or veterinary use.
Overview
Key Takeaways
- TB-500 is a synthetic, N-acetylated heptapeptide corresponding to residues 17–23 (Ac-LKKTETQ) of the parent protein Thymosin Beta-4.
- It is frequently confused with full-length Thymosin Beta-4 — they have different CAS numbers, molecular weights and sequences. TB-500 is CAS 885340-08-9 (MW 889.02); full-length Tβ4 is CAS 77591-33-4 (MW 4963.44, 43 amino acids).
- TB-500 is investigational and unapproved. It is AU Schedule 4 and WADA-prohibited at all times.
Thymosin Beta-4 (Tβ4) is an endogenous, highly conserved 43-amino-acid polypeptide that acts as the primary monomeric G-actin-sequestering molecule in mammalian cells. TB-500 is a synthetic, N-terminal-acetylated heptapeptide fragment corresponding to residues 17 through 23 of Tβ4 (Ac-LKKTETQ).
This sequence represents the active site responsible for the parent protein's actin-binding and cell-migratory properties. It was first synthesised and characterised analytically by Esposito and colleagues in 2012, and has been studied in preclinical regenerative-medicine models.
Neither Tβ4 nor TB-500 is approved for human therapeutic use by the US FDA or the Australian TGA. In Australia these are Schedule 4 (Prescription Only) substances, and both are banned at all times under the WADA Prohibited List. Silverback Peptides supplies TB-500 for laboratory research only.
Fragment vs Full-Length: A Critical Distinction
Key Takeaways
- Many suppliers and datasheets mislabel TB-500 with the full-length Tβ4 CAS number (77591-33-4). This is incorrect.
- TB-500 (the fragment) = CAS 885340-08-9, MW 889.02, sequence Ac-LKKTETQ.
- Full-length Thymosin Beta-4 = CAS 77591-33-4, MW 4963.44, 43 amino acids.
This distinction matters for analytical accuracy. Published human clinical programs — such as the RGN-259 ophthalmic trials — used full-length Thymosin Beta-4, not the TB-500 fragment. Conflating the two leads to misattributed evidence: clinical data for the parent protein does not automatically apply to the heptapeptide fragment.
Mechanism of Action
TB-500's primary mechanism relies on its interaction with the cellular cytoskeleton. The LKKTET motif binds monomeric globular actin (G-actin) in a 1:1 ratio with a dissociation constant (Kd) of approximately 0.5 to 0.7 µM, preventing G-actin from polymerising into filamentous actin (F-actin).
By maintaining a dynamic pool of unpolymerised actin monomers, the peptide enables rapid cytoskeletal remodelling. In research models this has been associated with:
- Directed migration of keratinocytes and dermal fibroblasts toward injury sites.
- Endothelial cell sprouting and tube formation during angiogenesis.
- Mobilisation of cardiac progenitor and mesenchymal stem cells.
- Activation of endothelial nitric oxide synthase (eNOS) promoting local vasodilation.
State of the Evidence
Key Takeaways
- There are no completed, published, randomised human trials of the TB-500 fragment itself.
- A Phase 1/2 trial (NCT07487363) of TB-500 in cardiovascular disease was initiated in February 2026 — no data reported yet.
Preclinical work (e.g. Philp et al., 2004) showed that a synthetic heptapeptide containing the actin-binding domain accelerated dermal re-epithelialisation comparably to the full-length parent molecule in animal wound models, suggesting the core sequence is sufficient to drive repair.
However, there are no completed, published, randomised, double-blind human clinical trials of the synthetic fragment TB-500. In February 2026 a Phase 1/2 trial (NCT07487363) was initiated to evaluate safety and pharmacokinetics of TB-500 in adults with stable cardiovascular disease, but no clinical data has been reported yet.
Storage & Handling
Lyophilised TB-500 should be stored desiccated at −20°C or −80°C. Reconstitute with sterile 0.9% sodium chloride or bacteriostatic water and store the solution at 2–8°C, protected from light.
Avoid high-temperature exposure and repeated freeze-thaw cycles to prevent chemical degradation.
References
- [1] Esposito S, Deventer K, Goeman J, et al. Synthesis and characterization of the N-terminal acetylated 17-23 fragment of thymosin beta 4 identified in TB-500. Drug Test Anal. 2012;4(9):733-738. DOI ↗
- [2] Philp D, Nguyen M, Scheremeta B, et al. Thymosin beta4 promotes angiogenesis, wound healing, and hair follicle development. Mech Ageing Dev. 2004;125(2):113-115. DOI ↗
- [3] Malinda KM, Sidhu GS, Mani H, et al. Thymosin beta4 accelerates wound healing. J Invest Dermatol. 1999;113(3):364-368. DOI ↗