TB-500 Fragment (17-23)

Also known as: TB4 fragment 17-23, Ac-LKKTETQ, LKKTETQ, Thymosin beta-4 actin-binding fragment, 885340-08-9

Evidence: Preclinical

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Overview

Ac-LKKTETQ, the actin-binding heptapeptide of Thymosin Beta-4, studied in animal models for cell migration, angiogenesis, wound healing and tissue repair.

Ac-LKKTETQ, the acetylated actin-binding heptapeptide at residues 17 to 23 of thymosin beta-4. It is the same molecule as the catalog entry TB-500 (id 10): analysis of commercial TB-500 identified exactly this fragment (Esposito 2012), so this is a duplicate listing, not a distinct compound. The fragment carries the angiogenic activity of the parent protein. Peptides missing any part of the motif were inactive, while the heptapeptide matched the full protein at about 50 nM in endothelial migration and chick aortic-arch sprouting (Philp 2003a), and promoted dermal repair in aged mice as well as the protein did (Philp 2003b). Claims of better bioavailability than the full protein have no pharmacokinetic support; the one metabolism study found rapid degradation and suggested the metabolite Ac-LKKTE carries the activity (Rahaman 2024).

Benefits

Angiogenesis and endothelial migration matching full-length thymosin beta-4 at about 50 nM (in vitro and chick aortic arch); dermal wound repair in aged mice (animal). No human data

Dosing reference

Research dose: 200 to 500 mcg daily: research-community range, no published human dose. The only published in-vivo dose is a single 10 mg administration in horses
Range: 200 to 500 mcg, 1x daily
Reconstitution: 2 mL bacteriostatic water
Common vial sizes: 5 mg

Subcutaneous in research use. The improved-bioavailability claim has no supporting data: no pharmacokinetic study of this peptide exists in any species, and in rats it was rapidly metabolized (Rahaman 2024). Same molecule as the TB-500 catalog entry (id 10), so dosing conventions are identical.

Mechanism

LKKTETQ is the G-actin-binding motif of thymosin beta-4. Using natural protein, proteolytic fragments and synthetic peptides, the seven-residue motif was shown to be necessary and sufficient for angiogenic activity: migration of human umbilical vein endothelial cells and chick aortic-arch sprouting were near-identical between the protein and the peptide at about 50 nM, peptides lacking part of the motif were inactive, and soluble actin at 5 to 50 nM blocked the effect (Philp 2003a). Activities mapped elsewhere in the protein do not transfer: Ac-SDKP and the 15-residue N-terminal site govern cell survival and apoptosis, and the ILK/PINCH/Akt pathway was shown for full-length protein in cardiomyocytes (Sosne 2010; Bock-Marquette 2004). Better tissue penetration from the smaller size is a plausible idea with no published measurement.

Evidence

Preclinical: animal or in vitro data only

The seven-residue actin-binding motif was necessary and sufficient for the angiogenic activity of thymosin beta-4, matching the full protein at about 50 nM in endothelial migration and aortic-arch sprouting, with activity blocked by soluble actin (Philp et al., 2003)
The synthetic LKKTETQ peptide promoted dermal wound repair in aged mice comparably to full-length thymosin beta-4 (Philp et al., 2003)
Mass spectrometry of commercial TB-500 identified its active ingredient as this same N-terminally acetylated 17-23 fragment (Esposito et al., 2012)
A single 10 mg dose in horses was detectable as parent peptide and metabolites in plasma and urine, the only published in-vivo administration of this peptide (Ho et al., 2012)
In rats and in human serum the parent peptide was rapidly metabolized, with Ac-LK the main early metabolite and only Ac-LKKTE showing significant wound-healing activity in fibroblasts (Rahaman et al., 2024)
Human-trial status: none. No trial of Ac-LKKTETQ has been published, and FDA states it has identified no human exposure data for the LKKTETQ fragment

References

Side effects

No human safety study of Ac-LKKTETQ has been published, and FDA states it has identified no human exposure data for this substance. Commonly reported by users: injection-site irritation and transient fatigue. Full-length thymosin beta-4, a different molecule, was well tolerated IV at up to 1260 mg daily for 14 days in 40 healthy volunteers (Ruff 2010). Because the motif promotes angiogenesis and cell migration, use with active or suspected malignancy is theoretically inadvisable.

Storage

Storage: Refrigerate 2-8°C (36-46°F)
Lyophilized: 2+ years at room temp, 3+ years refrigerated
Reconstituted: 28-30 days refrigerated

Pharmacology

Half-life: Not measured in any species. Rapidly metabolized in rat and human serum; metabolite Ac-LKK detectable in rat urine to 72 h (Rahaman 2024)
Molecular weight: 889.02 Da
Sequence: Ac-Leu-Lys-Lys-Thr-Glu-Thr-Gln (Ac-LKKTETQ, 7 aa; residues 17 to 23 of thymosin beta-4)

Stacks with

BPC-157