TB-500

Also known as: Ac-LKKTETQ, Thymosin beta-4 fragment 17-23, TB 500, Ac-Leu-Lys-Lys-Thr-Glu-Thr-Gln-OH, 885340-08-9

Evidence: Preclinical

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Overview

Acetylated heptapeptide Ac-LKKTETQ, the actin-binding region (residues 17 to 23) of thymosin beta-4 and not the full 43-residue protein; it promoted angiogenesis and wound repair in animal and cell models.

TB-500 is the acetylated heptapeptide Ac-LKKTETQ. Analysis of commercial TB-500 identified this fragment, residues 17 to 23 of thymosin beta-4, not the full 43-residue protein (Esposito 2012), so most thymosin beta-4 literature describes a different molecule. The fragment carries the actin-binding motif: it matched the full protein for endothelial migration and aortic-arch sprouting at about 50 nM, and promoted dermal repair in aged mice as well as the protein did (Philp 2003a; Philp 2003b). A 2024 study found it broken down rapidly in serum and suggested the wound-healing activity belongs to the metabolite Ac-LKKTE (Rahaman 2024). The catalog lists this molecule again as TB-500 Fragment (17-23), id 68. FDA lists it in the withdrawn-nomination table of its 503A compounding safety-risk page, noting no human exposure data.

Benefits

Tissue repair, faster wound healing, tendon and ligament recovery, reduced inflammation, hair regrowth (animal models)

Dosing reference

Research dose: 2 to 7.5 mg twice weekly: research-community range, no published human dose of the fragment. Horses received a single 10 mg dose in doping-detection work
Range: 2000 to 7500 mcg, 2x weekly (loading)
Reconstitution: 2 mL bacteriostatic water
Common vial sizes: 2 mg, 5 mg, 10 mg

Subcutaneous or intramuscular in research use. The loading-then-maintenance schedule is community convention with no published basis; no human pharmacokinetic study of Ac-LKKTETQ exists. In rats the parent peptide cleared quickly, with Ac-LK the main early metabolite and Ac-LKK still detectable at 72 h (Rahaman 2024).

Mechanism

The LKKTETQ motif is the actin-binding site of thymosin beta-4 and carries much of its activity: peptides missing any part of the motif were inactive in endothelial migration and chick aortic-arch sprouting assays, while the heptapeptide matched the full protein at about 50 nM (Philp 2003a). Through G-actin binding it supports cytoskeletal remodeling and cell migration; in aged mice the same heptapeptide raised wound contracture and collagen deposition like the full protein (Philp 2003b). Other activities mapped to thymosin beta-4 sit outside this motif, including the N-terminal Ac-SDKP sequence that promotes cell survival (Sosne 2010), so they should not be assumed for the fragment. The ILK/PINCH/Akt survival pathway was shown for the full protein in cardiomyocytes (Bock-Marquette 2004), not for Ac-LKKTETQ.

Evidence

Preclinical: animal or in vitro data only

Chemical analysis of commercial TB-500 identified its active ingredient as the N-terminally acetylated 17-23 fragment of human thymosin beta-4, Ac-LKKTETQ (Esposito et al., 2012)
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 (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)
In rats and in vitro, Ac-LKKTETQ was rapidly metabolized; only the metabolite Ac-LKKTE showed significant wound-healing activity in fibroblasts, which the authors read as the parent being a prodrug (Rahaman et al., 2024)
Full-length thymosin beta-4, a different molecule, was well tolerated in a randomized placebo-controlled IV study in healthy volunteers at 42 to 1260 mg single and 14-day daily dosing (Ruff et al., 2010)
Human-trial status: no trial of Ac-LKKTETQ has been published. Published human data cover full-length thymosin beta-4 only (phase 1 IV, phase 2 dermal ulcer and ophthalmic trials). FDA notes 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, transient fatigue, a brief head rush after dosing. 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: Refrigerated (2-8°C)
Lyophilized: 24+ months at room temperature
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)