TB-500

What TB-500 is and how it works

TB-500 is a commercial name, not a chemical one, and it does not always describe the same compound. Depending on the supplier it refers either to full-length synthetic thymosin beta-4 (Tβ4), a 43-amino-acid peptide with an acetylated N-terminus and a mass of about 4963 Da, or to a short fragment built around the actin-binding motif, such as the acetylated heptapeptide Ac-LKKTETQ, which weighs a little under 900 Da. The mass on the certificate of analysis tells you which one is in the vial. King Peptides lists its product as TB-500 (Thymosin Beta-4) 5 mg, so its certificate should show a mass close to 4963.5 Da.

Thymosin beta-4 was first isolated from calf thymus in the early 1980s, which explains the name, though it is not a thymus hormone in any narrow sense. It occurs in almost every cell type and is abundant in platelets and white blood cells. Inside the cell its main job is to bind G-actin, the single-molecule form of actin, in a one-to-one complex that keeps it out of actin filaments. By holding a reserve of monomers, Tβ4 lets a cell rebuild its actin skeleton quickly when it needs to move or change shape. The motif LKKTETQ, residues 17–23, is central to that binding.

Outside the cell, Tβ4 released by platelets and damaged tissue has been linked in cell and animal studies to cell migration, new blood-vessel formation, lower inflammation and less scarring. Its first four residues can also be cleaved off as Ac-SDKP, a separate small peptide studied in its own right for effects on blood-cell production and fibrosis. How much of the activity of the whole molecule a short fragment reproduces is unsettled, which is one more reason the label alone is not enough.

What the research on TB-500 and thymosin beta-4 shows

Most of the evidence concerns thymosin beta-4 itself rather than products sold as TB-500. Rat studies from the late 1990s found that Tβ4, applied to the skin or injected into the abdominal cavity, speeded up the closure of skin wounds and increased vessel growth in the wound bed. Later work extended the finding to diabetic and aged mice and to corneal injury in rodents. Evidence level: animal models.

The heart work drew the most attention. Bock-Marquette et al. (2004) reported that Tβ4 given to mice after a coronary artery was tied off improved the survival of heart muscle cells and preserved heart function, acting partly through integrin-linked kinase. Later mouse studies described Tβ4 activating progenitor cells in the outer layer of the heart and stimulating vessel growth; whether it also produces new heart muscle cells has been disputed by other laboratories. Evidence level: mouse models.

Human data come from early clinical trials of thymosin beta-4 formulations, not of TB-500. Eye drops were tested in dry eye and in neurotrophic keratopathy, a disorder of corneal healing; a topical gel was tested in chronic skin wounds; and an intravenous formulation went into a phase 1 safety study in healthy volunteers. The formulations were generally well tolerated over the short trial periods, the efficacy results were modest or mixed, and none has become an approved medicine. Products sold as TB-500 have not been tested in published controlled human studies at all.

TB-500 doses used in published research

The animal studies gave doses per animal or per kilogram that varied widely between models, and the human trials tested particular pharmaceutical formulations over short periods. None of that defines a dose for a TB-500 product, and no validated human dose exists for thymosin beta-4 or for any fragment of it. These are descriptions of study designs, not instructions.

TB-500 safety and side effects

The early thymosin beta-4 trials reported acceptable tolerability over short periods. They say little about repeated use of research products that may not even be the same molecule.

• Uncertain identity. A vial labelled TB-500 may hold full-length Tβ4 or a fragment, and data for one do not transfer to the other.
• Cell migration and vessel growth. The processes Tβ4 promotes are also used by tumours, and raised Tβ4 expression has been linked to invasiveness in experimental cancer models. Nothing shows that Tβ4 causes cancer; the concern is theoretical and untested.
• Short trials only. The human trials were short and used defined formulations. Long-term exposure has not been studied.
• Material quality. A 43-residue peptide is harder to synthesise cleanly than a short one, so HPLC purity and a matching mass are the minimum evidence of what a vial contains.

Regulatory status of TB-500 in Europe

Neither thymosin beta-4 nor any TB-500 product is authorised as a medicine in the European Union, and no thymosin beta-4 medicine has been approved elsewhere. Research material carries no marketing authorisation and is not intended for human use; rules on possession and import differ between member states.

In sport, thymosin beta-4 and its derivatives, TB-500 among them, are prohibited at all times under S2 of the World Anti-Doping Agency Prohibited List. TB-500 has also featured in doping cases in horse racing, where laboratories developed dedicated tests to detect it.

Sourcing TB-500 and checking quality

King Peptides sells TB-500 (Thymosin Beta-4) 5 mg as a single compound. TB-500 is also a component of the Wolverine Stack - BPC-157 + TB-500 5/5 mg, which pairs it with BPC-157, the gastric pentadecapeptide, and of the KLOW-80 Blend - GHK-Cu + BPC-157 + TB-500 + KPV. Why those pairings exist, and how thin the evidence for them is, is set out in our guide to peptide combinations in research. The other compounds studied for tissue repair are grouped in the repair and longevity section of our index.

For TB-500 more than for most peptides, the certificate is where you find out what you have. Check that the lot number matches the vial, that HPLC purity is at least 99% and that the mass is about 4963 Da for full-length thymosin beta-4; a mass under 1,000 Da means a fragment, whatever the label says. In a blend, each component should be identified by its own mass. King Peptides supplies a lot-specific certificate with HPLC and mass spectrometry and dispatches from the Netherlands; by the shop's own estimate delivery takes 1–2 business days within the Netherlands and 3–5 business days elsewhere in the EU, with no customs inside the EU. Our guides cover reading a certificate of analysis and storing lyophilised peptides at −20 °C.

TB-500: frequently asked questions

Is TB-500 the same as thymosin beta-4? Sometimes. The name is used both for full-length synthetic Tβ4 and for short fragments of it. The mass on the certificate settles which one a vial holds.

What does the actin-binding motif do? LKKTETQ, residues 17–23, is the part of Tβ4 central to binding actin monomers, which is how the peptide manages a cell's supply of actin for movement and shape change. Some suppliers sell that motif alone, acetylated, as TB-500.

Has TB-500 been tested in people? Not in published controlled studies. The early trials used pharmaceutical formulations of thymosin beta-4 as eye drops, a skin gel and an intravenous infusion, and none led to an approved medicine.

Is TB-500 banned in sport? Yes. Thymosin beta-4 and its derivatives, TB-500 included, are prohibited at all times under S2 of the WADA list, and TB-500 is also a prohibited substance in horse racing.