TB-500 vs Thymosin Beta-4
Research Comparison

Research Overview

TB-500 vs thymosin beta-4 compares a protein with a piece of it. Thymosin beta-4 is a 43-residue, 5 kDa peptide regarded as the main G-actin sequestering peptide in mammalian tissue (Philp et al., 2003). TB-500 is the name under which a doping-control laboratory identified Ac-LKKTETQ, residues 17 to 23 of that protein with an acetylated N-terminus (Esposito et al., 2012). The two differ about 5.6-fold in molecular weight, and nearly all published biology, including every human trial we found, concerns the full protein.

Is TB-500 the same as thymosin beta-4? In analytical and anti-doping work, no, though the name drifts elsewhere: a 2026 rat tendon study called its TB-500 synthetic thymosin beta-4 (Biçer et al., 2026).

Structure and Class

Human thymosin beta-4 (UniProt P62328, mature chain) is Ac-SDKPDMAEIEKFDKSKLKKTETQEKNPLPSKETIEQEKQAGES: 43 residues with an acetylated N-terminal serine, one methionine at position 6 and no cysteine; PubChem lists it as CID 16132341, titled timbetasin. It binds actin monomers one to one and blocks their polymerization (Safer et al., 1991). Its first four residues are also released as the tetrapeptide Ac-SDKP (CID 65938, 487.5 g/mol): prolyl oligopeptidase inhibitors reduced that release in kidney homogenates and lowered Ac-SDKP levels in rats (Cavasin et al., 2004).

TB-500 is defined in doping-control papers. A Ghent laboratory found the N-terminal acetylated 17 to 23 fragment of human thymosin beta-4 in a TB-500 formulation by high-resolution mass spectrometry and synthesized it on solid phase (Esposito et al., 2012). A Hong Kong racing laboratory called TB-500 a veterinary preparation whose key ingredient is LKKTETQ with artificial N-terminal acetylation, the segment it links to actin binding and cell migration (Ho et al., 2012). PubChem lists that fragment as CID 62707662, with TB-500 among its synonyms; unacetylated LKKTETQ is CID 10169788, at 847.0 g/mol.

The FDA uses the same definition. A page on bulk drug substances that may present significant safety risks lists "Thymosin beta-4, fragment (LKKTETQ), also known as TB-500" among withdrawn nominations formerly in category 2, citing possible immunogenicity and no human exposure data identified by FDA.

The Disguised Alpha product page names the product TB-500 (Thymosin Beta-4), a lyophilized powder labeled 10mg. Its class reads "Thymosin β-4 / fragment", and its description, headed "Thymosin Beta-4 Fragment", says the peptide is "modeled on regions linked to thymosin beta-4 activity". It also lists the formula and molecular weight of full-length thymosin beta-4 (C212H350N56O78S, 4963 g/mol). Confirm on each lot's certificate which molecule was identified.

Side by Side

Research Context: TB-500

Work on Ac-LKKTETQ itself is mostly analytical. The Hong Kong group mapped likely metabolites in vitro, then detected the parent peptide and its metabolites in equine urine and plasma after a single exposure (Ho et al., 2012). A 2024 study added human serum, enzyme systems and rats: Ac-LK was the main rat urinary metabolite over the first six hours, and Ac-LKK stayed detectable up to 72 hours (Rahaman et al., 2024). Models: in vitro systems, horses and rats.

Biological claims for TB-500 usually borrow from the motif. Comparing natural protein, fragments and synthetic peptides, one group found the seven-residue actin-binding motif matched the full protein in endothelial cell migration and chick aortic arch sprouting at about 50 nM; peptides lacking part of it were inactive (Philp et al., 2003).

The 2024 study notes that those activities were reported for unacetylated LKKTETQ and that effects of acetylated TB-500 had not been documented; in its fibroblast assays nothing was cytotoxic, and only the metabolite Ac-LKKTE gave a significant scratch-wound response (Rahaman et al., 2024). We found no human study of the acetylated fragment.

Research Context: Thymosin Beta-4

Most biology attached to the TB-500 name was measured with the full protein. In a rat full-thickness wound model, thymosin beta-4 raised re-epithelialization over saline controls by up to 61 percent at day 7 and stimulated keratinocyte migration two to three fold (Malinda et al., 1999).

In mouse heart cells it promoted migration and survival and formed a complex with PINCH and integrin-linked kinase that activates Akt; after coronary artery ligation in mice the study reported greater early myocyte survival and better cardiac function (Bock-Marquette et al., 2004). Models: rats, mice and cell culture. PubMed holds about 1,200 thymosin beta-4 records and about two dozen naming TB-500, mostly methods papers and reviews (October 2026).

Human research covers only the full protein. In a randomized, placebo-controlled phase 1 study, four cohorts of 10 healthy volunteers received synthetic thymosin beta-4 at one of four ascending amounts or placebo, once and then daily for 14 days; adverse events were infrequent and mild or moderate, none serious (Ruff et al., 2010). A placebo-controlled phase 2 study of a topical form in 73 participants with venous stasis ulcers found tolerability comparable to placebo; its authors called the efficacy findings suggestive of a possible effect at one strength (Guarnera et al., 2010).

In a phase 3 eye-drop trial in 18 participants with neurotrophic keratopathy, the persistent epithelial defect closed completely by week 4 in 6 of 10 on thymosin beta-4 and 1 of 8 on placebo (p = 0.0656, not significant), with a significant difference at day 43; employees of the developer co-designed the study (Sosne et al., 2022). Drugs@FDA lists no product containing thymosin beta-4 (openFDA search, October 2026).

Choosing Between Them for a Research Question

Start from the endpoint. Actin sequestration, the integrin-linked kinase pathway, dermal or cardiac models, Ac-SDKP formation, or any design meant to sit beside the published trials points to full-length thymosin beta-4, the molecule those papers used. Detection methods, metabolite work and doping-control reference material point to Ac-LKKTETQ. A question about the motif alone needs a decision on acetylation, since the motif data come from unacetylated LKKTETQ.

Then check the arithmetic: 10 mg is about 2.0 µmol of the full protein but about 11.2 µmol of the fragment, more than fivefold apart. Name the material by sequence, acetylation state and molecular weight, not by TB-500 alone.

Handling and Storage

The Disguised Alpha product page lists -20°C for the lyophilized powder as shipped and 2 to 8°C after reconstitution, protected from light, with freeze/thaw cycles avoided. For either molecule, let the sealed vial reach room temperature before opening, add diluent slowly down the wall, swirl rather than shake, and split stock into single-use aliquots labeled with the lot number.

The two fail differently. Thymosin beta-4 has one methionine, at position 6, and oxidation there adds 16 mass units; Ac-LKKTETQ has no methionine or cysteine. In tissue homogenates, the full protein can yield Ac-SDKP through prolyl oligopeptidase (Cavasin et al., 2004), so tetrapeptide assays should allow for that source. Use the certificate's molecular weight for molarity.

Questions Researchers Ask

Is TB-500 the same as thymosin beta-4?

Not by the doping-control definition: TB-500 as analyzed is Ac-LKKTETQ, about 889 g/mol (Esposito et al., 2012), while thymosin beta-4 is the 43-residue protein at about 4963 g/mol. Some authors apply the name to the full protein (Biçer et al., 2026), so check each lot's certificate in the COA portal.

TB500 vs TB4: which one has human data?

Only TB4, the full protein, from a phase 1 study in healthy volunteers (Ruff et al., 2010) to a phase 3 eye-drop trial (Sosne et al., 2022). We found no human study of the acetylated fragment, and FDA says it has identified no human exposure data for it.

Does the fragment act like the full protein?

Partly. The seven-residue motif matched the full protein in endothelial migration and sprouting assays (Philp et al., 2003), but effects of the acetylated form were undocumented as of 2024, and in fibroblasts only its metabolite Ac-LKKTE gave a significant scratch-wound response (Rahaman et al., 2024).

Is TB-500 prohibited in sport?

Yes. The WADA 2026 Prohibited List names "Thymosin-β4 and its derivatives e.g. TB-500" under S2.3, growth factors and growth factor modulators, in class S2, which is prohibited at all times.

TB4 vs TB500: what does the Disguised Alpha listing show?

The TB-500 (Thymosin Beta-4) page lists the peptide class as thymosin β-4 / fragment and gives the formula and molecular weight of full-length thymosin beta-4. Each lot's certificate is published on that page and in the COA portal.