Thymosin β4 fragment

TB-500 in Canada

Also known as Thymosin beta-4 fragment · Tβ4 (17-23) · Ac-LKKTETQ · TB500

TB-500 is the research-market name for a synthetic peptide derived from thymosin β4 (Tβ4), a 43-amino-acid actin-binding protein present in almost every human cell. The parent protein has a substantial, multi-laboratory preclinical literature in wound, corneal and cardiac-repair models and has been taken into human trials by a U.S. biotechnology company; the short synthetic fragment sold as TB-500 has very little published data of its own. Canada Peptides carries research-grade TB-500 in 2 mg and 5 mg vials and in a BPC-157 + TB-500 blend, priced and shipped in CAD for laboratory and research use only.

Quick facts

Class: Synthetic thymosin β4-derived peptide (actin-binding motif)
Structure: Parent Tβ4: 43 amino acids, ~4,963 Da. TB-500 as sold: the acetylated LKKTETQ actin-binding region (residues 17–23) or, from some suppliers, full-length Tβ4
Half-life: Short; minutes to low hours in plasma for the parent protein. No published PK for the research fragment
Route in research: Intraperitoneal, subcutaneous, intravenous, intracardiac and topical in animal studies; topical and intravenous in human Tβ4 trials
Cadence in research: Daily or every few days in animal models; loading-then-maintenance schedules in applied research
Storage: Lyophilised: refrigerated, dark. Reconstituted: refrigerated, used within weeks
Status in Canada

Pharmacology

Thymosin β4 is, first and foremost, an actin-sequestering protein. It binds monomeric globular actin (G-actin) one-to-one through the LKKTET motif and holds it in a pool from which cells can rapidly build filamentous actin when they need to change shape or move. That intracellular function is the foundation of everything else reported: cell migration, the spreading of keratinocytes and endothelial cells across a wound, and the reorganisation of the cytoskeleton during repair.

The extracellular effects are the ones the repair literature invokes. Tβ4 is released from platelets and damaged cells into wound fluid, where it has been reported to recruit keratinocytes and endothelial cells, promote angiogenesis, reduce inflammatory cytokine expression and limit apoptosis. In the 2004 Nature paper from Deepak Srivastava's group at UT Southwestern, Tβ4 activated integrin-linked kinase and promoted survival and migration of cardiac cells, and mice given Tβ4 after coronary ligation retained more cardiac function. A 2007 Nature paper from Paul Riley's laboratory reported that Tβ4 mobilised adult epicardial progenitor cells and induced new vessel growth. Neither study used a fragment; both used the full protein.

What the fragment retains is the open question. The LKKTETQ region reproduces actin binding in vitro and has been reported to promote cell migration and wound closure in some models, and the argument for the fragment is that the actin-binding motif is the "active site." The counter-argument is that Tβ4's extracellular effects may depend on the whole molecule, its N-terminal acetylation and its metabolite Ac-SDKP, none of which a seven-residue fragment carries.

Pharmacokinetically, Tβ4 is cleared quickly from plasma, and the applied literature — like that for BPC-157 — assumes that tissue effects outlast circulating levels. There is no published pharmacokinetic study of the TB-500 fragment in any species. The figures quoted online (roughly half an hour to a couple of hours) are extrapolations.

TB-500 FAQ

Is TB-500 for sale in Canada?

Yes. Research-grade TB-500 is available in Canada from Canada Peptides in 2 mg and 5 mg vials and in a BPC-157 + TB-500 blend, priced and shipped in CAD. It is supplied strictly for laboratory and research use, not for human consumption.

What is TB-500?

TB-500 is the research-market name for a synthetic peptide derived from thymosin β4, a 43-amino-acid actin-binding protein found in nearly all human cells. Depending on the supplier it is either the short acetylated actin-binding fragment (Ac-LKKTETQ) or the full-length protein; the certificate of analysis tells you which.

What is the difference between TB-500 and thymosin β4?

Thymosin β4 is the natural 43-amino-acid protein and the subject of almost all the published research, including human trials by RegeneRx. TB-500 is a synthetic product name, originally describing the seven-residue actin-binding fragment. Whether the fragment reproduces the parent protein's effects has not been established in controlled studies.

What does the research on TB-500 actually show?

For full-length thymosin β4: independently replicated animal data in skin-wound, corneal and cardiac-repair models, and human trials in dry eye, neurotrophic keratopathy and chronic wounds with mixed results and no approved product. For the TB-500 fragment: very little controlled data in any species.

What is the half-life of TB-500?

Short. The parent protein is cleared from plasma within minutes to a few hours, and effects in repair models are assumed to depend on tissue-level activity rather than circulating peptide. There is no published pharmacokinetic study of the TB-500 fragment; the figures quoted online are extrapolations.

How was TB-500 dosed in studies?

Published studies mostly used full-length thymosin β4: microgram quantities applied topically to wounds, hundreds of micrograms per animal intraperitoneally in mouse cardiac models, and 0.1 % eye drops or 0.01–0.1 % gels in human trials. There is no validated human dose for TB-500, and this page does not recommend one; the material sold here is for research use only.

What side effects does TB-500 research report?

Early-phase human trials of full-length thymosin β4 by intravenous, topical and ophthalmic routes reported no dose-limiting toxicity and placebo-like adverse-event rates. The fragment has no controlled safety data. Theoretical concerns include effects on tumour growth, given thymosin β4's role in cell migration, and on platelet function; neither has been demonstrated or excluded.

Is TB-500 legal in Canada?

TB-500 is not a controlled substance in Canada, but it has no Health Canada approval for human use and no DIN. It may be sold for laboratory research, which is how it is sold here. It is prohibited for tested athletes under WADA's S2 category, which names TB-500 explicitly.

Research references

Complete amino acid sequence of bovine thymosin beta 4: a thymic hormone that induces terminal deoxynucleotidyl transferase activity in thymocyte populations. Proceedings of the National Academy of Sciences, 1981.Original sequencing of the 43-residue parent protein from the Goldstein laboratory.View record ↗

Thymosin beta 4 and Fx, an actin-sequestering peptide, are indistinguishable. Journal of Biological Chemistry, 1991.Establishes Tβ4 as the major G-actin sequestering molecule — the basis of the actin-binding mechanism.View record ↗

Thymosin beta4 accelerates wound healing. Journal of Investigative Dermatology, 1999.NIH study in rats that started the dermal wound-healing line; source of the topical 5 µg dose.View record ↗

Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature, 2004.Mouse coronary-ligation study establishing the cardiac-repair claim for full-length Tβ4.View record ↗

Thymosin beta4 induces adult epicardial progenitor mobilization and neovascularization. Nature, 2007.Independent group; reports vessel formation from epicardial progenitors after Tβ4 in mice.View record ↗

Thymosin beta4: actin-sequestering protein moonlights to repair injured tissues. Trends in Molecular Medicine, 2005.Review of the repair biology and the early clinical programme, from the originating laboratory.View record ↗

Doping control analysis of TB-500, a synthetic version of an active region of thymosin β4, in equine urine and plasma by liquid chromatography-mass spectrometry. Journal of Chromatography A, 2012.Characterises TB-500 as the Ac-LKKTETQ fragment and documents its use and detection in racehorses.View record ↗

Thymosin Beta 4 ophthalmic solution for dry eye: a randomized, placebo-controlled, Phase II clinical trial conducted using the controlled adverse environment (CAE) model. Clinical Ophthalmology, 2015.Example of the RegeneRx human programme; full-length Tβ4 eye drops, not the fragment.View record ↗

TB-500 in Canada

Quick facts

TB-500 — for sale in Canada

What is TB-500?

Evidence at a glance

Pharmacology

Identity and chemistry

Storage and stability

Research indications

Research protocols

Interactions and stacking in research

Reconstitution and handling

Side effects and safety signals

Regulatory status in Canada

Further reading

TB-500 FAQ

Research references