TB4-FRAG — Research Dossier
Evidence grading
Parent protein
Thymosin β4
43-amino-acid actin-sequestering protein
Common fragment
Ac-SDKP (1–4)
N-terminal tetrapeptide; anti-fibrotic/anti-inflammatory activity
Actin motif
LKKTETQ (17–23)
Overlaps functionally with TB-500 (Tβ4 17–23)
Human efficacy trials
0
All human data attaches to full-length recombinant Tβ4
TB4-FRAG denotes at least two structurally and mechanistically distinct sequences from thymosin β4 — the anti-fibrotic Ac-SDKP tetrapeptide and the actin-binding LKKTETQ heptapeptide — and this distinction must be confirmed per SKU before relying on any of the evidence below.
Thymosin β4 (Tβ4) is a 43-amino-acid actin-sequestering protein with roles in tissue protection and repair. Enzymatic cleavage and synthetic production yield several short fragments marketed under the "TB4-FRAG" label, most often two sequences with different mechanisms and target applications. This naming ambiguity is the essential context for this dossier.
TB4-FRAG as sold in the research market most often refers to Tβ4(1–4) — the N-terminal tetrapeptide Ac-SDKP (N-acetyl-Ser-Asp-Lys-Pro). This fragment lacks the actin-binding and cell-migration domain; its activity is oriented toward anti-inflammatory and anti-fibrotic pathways. The seven-residue actin-binding motif Tβ4(17–23) — LKKTETQ — is the sequence that TB-500 replicates and should be cross-referenced with that dossier rather than duplicated here.
“Ac-SDKP is naturally generated from thymosin β4 by meprin-α then prolyl oligopeptidase, and cleared by the N-domain of ACE — which is why ACE inhibitors raise endogenous Ac-SDKP concentrations in plasma and tissues.”
— Liu JM et al., mechanistic characterisation of Ac-SDKP
Which molecule? — naming caveat
At least two structurally distinct sequences are sold as "TB4-FRAG":
- Tβ4(1–4) — Ac-SDKP (N-acetyl-Ser-Asp-Lys-Pro). The N-terminal tetrapeptide. Lacks the actin-binding and cell-migration domain. Oriented toward anti-inflammatory and anti-fibrotic activity. This is the fragment most commonly sold specifically as "TB4-FRAG" or "Tβ4 Fragment 1–4."
- Tβ4(17–23) — LKKTETQ. The seven-residue actin-binding motif essential for Tβ4 angiogenic activity. This is the sequence that TB-500 replicates. A product labelled as the "17–23" fragment overlaps conceptually with TB-500 and should be cross-referenced with that dossier, not treated as a separate compound.
The two sequences have different mechanisms, different target applications, and different evidence bases. Confirm which sequence a given product actually contains before relying on the evidence below.
Mechanism
Ac-SDKP (1–4)
Naturally generated from Tβ4 by meprin-α then prolyl oligopeptidase, and cleared by the N-domain of ACE — which is why ACE inhibitors raise endogenous Ac-SDKP. It shows anti-fibrotic activity across heart, lung, kidney, and liver in animal models by reducing fibroblast-to-myofibroblast conversion and TGF-β signalling, and has reported angiogenic activity in vitro and in vivo.
LKKTETQ (17–23)
The actin-binding motif essential for Tβ4 angiogenic activity. In endothelial migration and vessel-sprouting assays, the motif shows near-identical activity to full-length Tβ4 at approximately 50 nM, while peptides lacking part of the motif are inactive. This is the mechanistic basis of TB-500.
Evidence base and regulatory status
The fragment-specific evidence is preclinical. Most human clinical data for the Tβ4 family attaches to full-length recombinant Tβ4 (wound healing, dry eye indications), not to the short fragments. There are no completed human efficacy trials for either TB4-FRAG sequence specifically.
No approval from any major regulator for any Tβ4 fragment. Material supplied for laboratory work is research-use-only. Evidence grade: preclinical — mechanistically well-defined at the fragment level, with coherent animal anti-fibrotic (Ac-SDKP) and angiogenic (LKKTETQ) data, but no human efficacy trials for the fragments themselves.
See also
References
- 1
Malinda KM, et al. Thymosin β4 accelerates wound healing FASEB J 1999.
- 2
Philp D, et al. The actin-binding site on thymosin β4 promotes angiogenesis FASEB J 2004. PMID: 14500546
- 3
Huff T, et al. β-Thymosins, small acidic peptides with multiple functions J Mol Biol 2001.
- 4
Goldstein AL, et al. Thymosin β4: actin-sequestering protein moonlights to repair injured tissues Ann N Y Acad Sci 2007.
- 5
Liu JM, et al. Ac-SDKP angiogenic activity in vitro and in vivo Blood 2003.
Research & Laboratory Use Only
This dossier is compiled for research planning and educational purposes only. It summarises published scientific literature and does not constitute medical advice, dosing guidance, or a therapeutic claim. All Nexyra Lab products are for research purposes only and are not for human or veterinary use. Nothing in this document should be interpreted as recommending, endorsing, or facilitating the self-administration of any compound.
A one-time legal review of this template and disclaimer is recommended before the Journal section is made publicly accessible, given the health-adjacent nature of this content.
