RESEARCH LEDGER / Ac-LKKTETQ · THYMOSIN BETA-4 FRAGMENT
TB-500 is the Ac-LKKTETQ actin-binding fragment of thymosin beta-4, reconciled study by study.
A precise reading of the published record: the structure that is established, the wound and cardiac findings carried by the parent protein, and the human-data line that stays open. Every figure matched to its source.
The compound, in one reconciled line
TB-500 is the synthetic, N-acetylated heptapeptide Ac-LKKTETQ — molecular weight 889.02 Da, formula C38H68N10O14 — corresponding to residues 17–23 of thymosin beta-4 (Tβ4), the body's principal actin-sequestering peptide [1]. That short stretch is the conserved actin-binding motif of the beta-thymosins. The full-length thymosin beta-4 parent protein is a ~4963 Da, 43-residue molecule [5]; TB-500 is only its 7-amino-acid actin-binding core, sold and assayed under a research and veterinary designation.
That distinction is the whole reading. Across the literature, the headline efficacy findings — accelerated wound re-epithelialization, cardiac survival signaling, neurological recovery after stroke — were generated with full-length Tβ4, not the isolated 7-mer [7][6][8]. The structural fact that thymosin beta-4 binds monomeric G-actin 1:1 is established by crystallography [1]. Whether the fragment reproduces the parent protein's repair effects at the doses circulated in peptide research has not been settled in any controlled human trial [10].
This page keeps those two columns separate: what is matched to the fragment or to a hard structural result, and what was measured on the full-length protein. The TB-500 mechanism of action is the cleanest place to start, because the actin-binding motif is the one thing the 7-mer demonstrably carries.
TB-500 Peptide: What the Ac-LKKTETQ Fragment Is
The TB-500 peptide is a single research compound, not a blend. Its sequence is Ac-Leu-Lys-Lys-Thr-Glu-Thr-Gln-OH — seven residues, N-terminally acetylated, ~889 Da. In commerce and in the anti-doping literature, "TB-500" denotes this heptapeptide [1]. The same designation has been marketed as TB1000 in veterinary contexts.
The motif is a WH2-type actin-binding region — the structural class that includes monomer-sequestering proteins across the cytoskeleton [1]. Foundational biochemistry characterized thymosin beta-4's interaction with muscle and platelet actin and established its role buffering the unpolymerized actin pool [2].
One caveat is structural and worth stating plainly: the fragment does not generate Ac-SDKP, an N-terminal cleavage product of full-length Tβ4 with its own anti-fibrotic and angiogenic activity [5]. That product comes from a different region of the parent protein, so any Ac-SDKP-attributed effect is not a fragment effect.
What the literature actually establishes
X-ray crystallography of a gelsolin-domain-1–Tβ4 hybrid bound to actin, resolved at 2 Å, established that thymosin beta-4 forms a 1:1 complex with G-actin and sequesters the monomer by capping both ends, preventing polymerization [1]. That is the matched, fragment-relevant structural result — the actin sequestration and the LKKTETQ motif the fragment carries is the part doing the binding.
The regenerative findings are larger but sit in the full-length column. In a rat full-thickness wound model, topical or intraperitoneal Tβ4 increased re-epithelialization by 42% at four days and up to 61% at seven days versus saline, and as little as 10 pg stimulated keratinocyte migration two- to three-fold [7]. In mice, Tβ4 activated PINCH–integrin-linked-kinase–Akt survival signaling and improved cardiac function after coronary artery ligation [6]. A randomized, placebo-controlled Phase 1 study gave intravenous synthetic Tβ4 to 40 healthy volunteers at 42, 140, 420 or 1260 mg and reported good tolerability with no dose-limiting toxicities [10].
Every one of those human and animal results used the full protein. The TB-500 research findings page tags each study by which molecule was tested.
Where the human-data line stays open
There are no completed controlled clinical trials of the TB-500 heptapeptide for any indication [10]. Human data exist only for full-length Tβ4 — the Phase 1 intravenous safety study above, plus topical ophthalmic Tβ4 (RGN-259) dry-eye trials [10]. No validated human pharmacokinetic half-life exists for the 7-mer; what little is known about TB-500 half-life comes from anti-doping work in equine matrices, characterized for detection rather than for human PK [1].
The honest gaps go on the record alongside the findings. A 2026 Sports Medicine review of approved and unapproved peptide therapies — which lists TB-500/thymosin beta-4 among the unapproved peptides — concluded that many show favorable tissue-repair outcomes in animal models but that rigorous human safety data are scarce, with potential for serious harm, and that such compounds operate largely outside regulatory oversight [11].
TB-500 is not an FDA-approved drug, and the FDA has placed it in a 503A compounding category that carries a safety flag. Readers asking is TB-500 FDA approved will find the answer is no; the TB-500 legal status and 503A access page reads that standing from the primary source.