TB-500 (Thymosin Beta-4 fragment)

TB-500 is a trade name that circulates in gray-market peptide sales, and the most important fact about it is that the name does not specify a molecule. Chemically it usually refers to a synthetic, N-acetylated copy of a seven-amino-acid stretch of thymosin beta-4 — the sequence LKKTETQ, residues 17–23 of the parent protein — but the label has also been applied to full-length thymosin beta-4 (Tβ4), a 43-amino-acid protein that is a genuine research subject with registered clinical trials.

Evidence tier: preclinical — for the thing sold as TB-500. The parent protein has run phase 2 and phase 3 trials. The first registered human study of the 17–23 fragment itself, a phase 1/2 dose-escalation trial in 80 adults with stable atherosclerotic cardiovascular disease, began recruiting in February 2026 and is scheduled to finish in 2028 (NCT07487363). Everything else claimed for TB-500 is borrowed from Tβ4 literature.

There is also a harder problem than sequence ambiguity: the Racing Medication and Testing Consortium had the University of California–Davis Kenneth L. Maddy Laboratory analyze a batch of TB-500-labeled products and reported that many contained no thymosin beta-4 or any peptide derived from it — most contained no proteins, peptides, or amino acids at all. One sample did contain N-acetylated LKKTETQ (RMTC Thymosin β4 Bulletin). Gray-market "TB-500" has no standardized identity, which is the honest starting point for reading anything else about it.

The mechanism story belongs to thymosin beta-4, which is one of the better-characterized small proteins in cell biology.

• Actin sequestration. Tβ4 binds monomeric (G-)actin in a 1:1 complex and inhibits its polymerization into filaments — the property that originally identified it, when the actin-sequestering peptide "Fx" was shown to be identical to thymosin beta-4 (Safer et al., J Biol Chem 1991). By holding a reserve pool of unpolymerized actin, it lets cells rebuild their cytoskeleton quickly — which is what moving cells do.

• Where the fragment comes from. Mutational mapping split the actin-binding site into two parts: an N-terminal α-helix using a hydrophobic patch, and a separate hexapeptide motif at residues 17–22, with lysines 14 and 18 making the electrostatic contacts (Van Troys et al., EMBO J 1996). The 17–23 segment sold as TB-500 is that motif.

• Angiogenesis. Using proteolytic fragments and synthetic peptides, the seven-amino-acid actin-binding motif was shown to be essential for Tβ4's angiogenic activity in migration and vessel-sprouting assays (Philp et al., FASEB J 2003) — the single strongest argument that the fragment is not a random piece of the protein.

• Cell migration and healing. Tβ4 stimulated keratinocyte migration 2–3-fold with as little as 10 pg added, and increased reepithelialization of rat full-thickness wounds by 42% at four days and 61% at seven days (Malinda et al., J Invest Dermatol 1999).

• Cardiac signaling. Tβ4 forms a complex with PINCH and integrin-linked kinase, activating Akt; after coronary artery ligation in mice it improved early myocyte survival and cardiac function (Bock-Marquette et al., Nature 2004).

The mechanism section is also where the fragment-versus-protein distinction bites. Part of Tβ4's biology runs through Ac-SDKP, an anti-inflammatory, antifibrotic tetrapeptide cleaved out of the N-terminus by meprin-α followed by prolyl oligopeptidase (Kumar et al., Am J Physiol Renal Physiol 2016). A peptide that starts at residue 17 cannot produce it. "TB-500 is thymosin beta-4" is wrong in both directions: the fragment carries some of the parent's activity and none of its N-terminal chemistry.

Neither TB-500 nor thymosin beta-4 has an approved human indication anywhere. Tβ4 has been developed as a clinical candidate — ophthalmic RGN-259 for dry eye, topical formulations for dermal wounds, injectable recombinant Tβ4 after myocardial infarction — but none has reached the market.

The TB-500 label lives in two commercial worlds. One is human "research chemical" sales, aimed at tendon, ligament, and soft-tissue complaints. The other is equine: the RMTC bulletin documents the acetylated LKKTETQ peptide being synthesized and marketed for horses at roughly $150–300 per 10 mg, with claims spanning muscle building, recovery, bleeding, red blood cells, and inflammation (RMTC). That market is where regulators first had to build detection methods.

The WADA Prohibited List names TB-500 explicitly, alongside FGFs, HGF, IGF-1, MGFs, PDGF, and VEGF, and the "and its derivatives" phrasing means the identity ambiguity above is not a loophole. Prohibition applies in and out of competition. Real cases have followed:

• Essendon Football Club (AFL), 34 players. ASADA alleged doping through use of thymosin beta-4 during the club's 2012 supplements program; the AFL Anti-Doping Tribunal cleared the players in March 2015, WADA appealed, and in January 2016 the Court of Arbitration for Sport imposed two-year bans commencing 31 March 2015, with credit for time already served, so most suspensions ended in November 2016 (WADA statement, 11 January 2016). No player returned a positive test — the case was built on non-analytical evidence.

• Emma Brooks (volleyball), four years. The Canadian Centre for Ethics in Sport announced in April 2025 that the U SPORTS athlete used BPC-157 and TB-500 between August and September 2024; she did not dispute the violation, and her ineligibility runs to 3 December 2028 (Sport Integrity Canada).

• Anthony McCauley (triathlon), four years. A whistleblower tip led USADA to evidence that he possessed and used BPC-157 and TB-500, and promoted prohibited substances on social media — treated as attempted complicity. His ineligibility began 9 September 2025, with results disqualified back to 1 June 2024 (USADA announcement).

• Horse racing. Thymosin β4 is banned by racing and equestrian authorities, and because the horse produces it endogenously, testing required a population study of normal blood levels; investigators reported that a non-natural synthesis impurity is detectable in equine plasma after a single dose of a TB-500 product (Delcourt et al., Drug Test Anal 2025).

The recurring lesson: no positive test is required. Admitted use, documented possession, or investigative evidence has been sufficient in every case above.

There is no human safety dataset for the TB-500 fragment given by injection. That is not a hedge — it is why NCT07487363 lists safety, tolerability, and pharmacokinetics as its objectives in a sequential dose-escalation design in 2026. What exists today:

• Parent-protein trials were tolerated. Tβ4 ran placebo-controlled phase 2 wound trials and multiple ophthalmic trials without reported dose-limiting toxicity (Sosne & Ousler, Clin Ophthalmol 2015) — but as topical and ophthalmic formulations, not multi-milligram subcutaneous injections.

• Informal reports center on injection-site reactions, headache, and fatigue, with unknown incidence and causality.

• A theoretical pro-angiogenic concern. The fragment's best-documented property is promoting new blood-vessel growth (Philp et al. 2003). No study shows it causes or accelerates tumors; none has been designed to rule it out either.

• Product identity is the concrete risk. When regulator-commissioned testing finds most sampled vials contain no peptide at all, the real exposure is to an unverified solution (RMTC).

For general framing, see what are the risks of peptides.

No human pharmacokinetics have been published for the 17–23 fragment — absorption, half-life, and clearance are being measured for the first time in the 2026 phase 1/2 study (NCT07487363). There is therefore no dose that any regulator, label, or completed trial supports.

Material is supplied as lyophilized powder, so the delivered amount depends entirely on the diluent volume chosen — and on the vial containing what the label says. More detail: TB-500 dosing education.

TB-500 is sold as lyophilized powder and, increasingly, inside blends — most often with BPC-157, sometimes with GHK-Cu and KPV added. Blends compound the identity problem: a single vial now depends on four uncertain contents instead of one.

The one head-to-head animal comparison is informative. In 32 rats with transected and repaired Achilles tendons, TB-500 at 60 µg/kg/day produced a statistically significant increase in maximum load to failure and significantly better Bonar and Movin histology scores versus controls, while BPC-157 at 10 µg/kg/day improved scores numerically without reaching significance — and the combination conferred no additional benefit over either agent alone (Biçer et al., Jt Dis Relat Surg 2026). Note that this peer-reviewed paper calls its test article "synthetic thymosin beta-4 (TB-500)": the naming conflation runs through the literature too. Full breakdown: BPC-157 vs TB-500.

Human trials of thymosin beta-4 (the parent protein, mostly not by injection):

• Pressure ulcers — randomized, double-blind, placebo-controlled dose-response phase 2, n=72, completed December 2008 (NCT00382174, RegeneRx).

• Venous stasis ulcers — same design, n=72, completed January 2009 (NCT00832091).

• Epidermolysis bullosa — phase 2, n=30, terminated (NCT00311766).

• Dry eye, phase 2 (CAE model) — n=72 randomized 1:1 to 0.1% Tβ4 or placebo; neither primary endpoint was met, though several secondary measures favored treatment (CAE discomfort reduced 27%, P=0.0244; central corneal staining P=0.0075) (Sosne & Ousler 2015).

• ARISE-3, phase 3 dry eye — n=700, completed 2021 (NCT03937882). It did not meet its primary outcome measures; ocular grittiness improved on secondary analysis (P=0.0104, 0.0307, 0.0046) (RegeneRx topline release, March 2021).

• Acute myocardial infarction — recombinant human Tβ4 (NL005) phase 2b, n=90, completed May 2023 (NCT05984134).

Fragment-specific preclinical work is thinner but real: the LKKTETQ seven-mer promoted dermal repair in aged mice comparably to the full molecule (Philp et al., Wound Repair Regen 2003). For a synthesis of Tβ4 biology, see Goldstein et al., Expert Opin Biol Ther 2012. Study-by-study detail: TB-500 research and evidence.

• TB-500 potential benefits and areas of research
• TB-500 side effects and safety context
• TB-500 dosing education
• TB-500 research and evidence overview
• BPC-157 vs TB-500 comparison
• BPC-157 overview

Is TB-500 the same thing as thymosin beta-4? No. Thymosin beta-4 is a 43-amino-acid protein your cells make; TB-500 is normally a synthetic copy of its residues 17–23 (LKKTETQ). The fragment reproduces the actin-binding and angiogenic functions (Philp 2003) but cannot generate Ac-SDKP, which is cleaved from the protein's opposite end (Kumar 2016). Vendors and some published papers use the names interchangeably; that is a labeling habit, not chemistry.

What is actually in a vial sold as TB-500? Not reliably knowable. Testing by the UC Davis Maddy Laboratory for the Racing Medication and Testing Consortium found that many TB-500-labeled products contained no thymosin beta-4 or derived peptide, and most contained no protein, peptide, or amino acid at all; one sample did contain N-acetylated LKKTETQ (RMTC bulletin).

Has TB-500 been tested in humans? The fragment, essentially not — until now. A phase 1/2 randomized, placebo-controlled dose-escalation study of TB-500 in 80 adults with stable atherosclerotic cardiovascular disease started recruiting in February 2026, with estimated completion in 2028 (NCT07487363). The parent protein has completed phase 2 wound trials and phase 3 dry-eye trials, and the phase 3 program missed its primary endpoints.

Is TB-500 banned in sport? Yes, at all times. It is named in category S2.3 of the WADA Prohibited List as "Thymosin-β4 and its derivatives e.g. TB-500." Sanctions include 34 Essendon AFL players (two years each, imposed by CAS in 2016 with no positive tests), a four-year ban for volleyball player Emma Brooks running to December 2028, and a four-year USADA sanction for triathlete Anthony McCauley beginning September 2025.

How does TB-500 compare with BPC-157? Different origins — TB-500 from an actin-binding protein, BPC-157 from a gastric protein fragment — but similar market positioning and the same prohibited status. In the only published head-to-head rat tendon study, TB-500 reached statistical significance on load-to-failure and histology where BPC-157 did not, and the combination added nothing (Biçer et al. 2026). See the full comparison.

Does TB-500 heal tendons and injuries? In rats, a tendon benefit has been measured at four weeks. In humans, nothing has been measured. The gap between those two sentences is the entire honest answer.

Why do horse-racing regulators care about it? It was marketed to horses first, with a documented weekly protocol (RMTC). Since horses make thymosin β4 naturally, laboratories had to establish baseline plasma concentrations and find a synthesis impurity to prove administration (Delcourt et al. 2025).

Is TB-500 legal to buy? It is not approved for human use anywhere and cannot legally be sold as a drug or supplement for people. It is sold as a "research chemical" labeled not for human consumption — labeling that shifts legal exposure to the buyer rather than making the product regulated.