TB-500 (Thymosin Beta-4): experimental tissue-repair peptide
A synthetic fragment of a natural healing protein that promotes tissue repair, new blood vessel growth, and reduces inflammation; experimental, not an approved drug.
A researcher, an agent, or an algorithm wrote down the sequence and picked a target to hit.
An AI model like OpenFold3 or AlphaFold built a 3D structure and scored how well it fits the binding site.
A second contributor repeated the computation on their own hardware and the scores matched.
FDA-tracked compound — synthesized for clinical/research use
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FDA-tracked (reclassified Category 1, Feb 2026) — preclinical/clinical bioassay data exists
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Snapshot
Class: Synthetic actin-binding heptapeptide; fragment of thymosin beta-4
Evidence tier: Animal-only evidence
Status: Not FDA approved for any indication. Removed from FDA 503A category 2 (April 22, 2026; nomination withdrawn). FDA intends to consult PCAC July 23, 2026 regarding TB-500 acetate and free-base forms — outcome pending; no compounding authorization in the interim. No approved human or veterinary pharmaceutical product exists. Historically distributed for equine veterinary use (Medivet, Australia); banned by FEI and multiple racing authorities. Per available sources, WADA prohibition under S2 (Peptide Hormones, Growth Factors, Related Substances and Mimetics) at all times since 2011; current list status not independently refreshed in this card.
Best-supported effect: Wound healing, tissue repair, and anti-inflammatory effects in animal models — documented overwhelmingly in studies using full-length thymosin beta-4 (the 43-aa parent protein); fragment-specific controlled animal evidence is limited.
Evidence context: TB-500 is a 7-amino acid synthetic fragment, not the 43-aa thymosin beta-4 protein. The full-length parent molecule has a legitimate clinical development history in ophthalmology and wound healing (RegeneRx Phase II programs), but those trials used topical formulations of the complete protein — a different compound and route — and cannot be used to support efficacy claims for the injectable heptapeptide fragment. published literature explicitly states zero controlled human trials for TB-500 specifically as of 2026.
Main caveat: The two compounds labeled interchangeably in commercial and community contexts — "TB-500" (7 aa, Ac-LKKTETQ-OH, ~889 Da) and "thymosin beta-4" (43 aa, ~4963 Da) — are chemically and pharmacokinetically distinct. Whether the fragment recapitulates the full protein's biology at comparable magnitude is the unresolved central question for TB-500. No human trial has tested this.
What this is
TB-500 is a synthetic heptapeptide with the sequence Ac-LKKTETQ-OH — the actin-binding active site of thymosin beta-4 (Tβ4), a 43-amino acid protein found in virtually every nucleated mammalian cell. TB-500 corresponds to positions 17–23 of the full Tβ4 sequence and is N-terminally acetylated to resist proteolytic degradation. Despite widespread interchangeable labeling in commercial supply chains and community contexts, TB-500 and full-length Tβ4 are chemically and pharmacokinetically distinct: TB-500 is the fragment; Tβ4 is the full-length parent protein.
Thymosin beta-4 was first isolated from bovine thymus in 1981 by Low and Goldstein at NIH, and subsequently established as a central G-actin-sequestering protein by Kleinman's group at the National Institute of Dental and Craniofacial Research. TB-500 entered the market not through a pharmaceutical development program but through the equine veterinary industry — Medivet (New South Wales, Australia) commercialized it for racehorse musculoskeletal recovery in the mid-2000s. No pharmaceutical company has actively pursued a clinical IND for the TB-500 heptapeptide; this is a peptide sequence synthesized from basic research into Tβ4's actin-binding domain, repurposed for veterinary and subsequently gray-market human use.
Full-length Tβ4 has advanced to Phase II clinical trials in ophthalmology (dry eye, neurotrophic keratopathy) and wound healing under RegeneRx Biopharmaceuticals (RGN-259, RGN-137). Whether that clinical track establishes proof of concept for the shorter synthetic fragment — and whether the fragment's shorter half-life and different tissue distribution preclude equivalent tissue-level effects — is the unresolved question at the center of TB-500's evidence landscape.
Evidence map
| Evidence layer | Grade | What it supports |
|---|---|---|
| Human | Not present (fragment-specific) | No completed human trials for TB-500 exist. Full-length recombinant Tβ4 has advanced through Phase I in healthy volunteers and Phase II trials in dry eye (RGN-259) and chronic wound healing (RGN-137) — these used the 43-aa parent protein via topical routes and cannot support efficacy claims for the TB-500 fragment. |
| Animal | Moderate (predominantly full Tβ4; fragment-specific limited) | Wound healing, cardiac progenitor cell activation, hair follicle stimulation, and anti-inflammatory effects across rodent and other species — overwhelmingly from studies using full-length thymosin beta-4. Equine veterinary use history exists for the TB-500 fragment but does not constitute controlled experimental data. |
| In vitro | Weak (mechanistic; doping-control characterization) | Actin-binding and G-actin sequestration documented for the fragment. WADA-commissioned in vitro and ex vivo studies characterized TB-500 fragment metabolism for doping-control purposes — established serial C-terminus cleavage pattern and N-terminal acetylation stability. |
| Computational | None identified | — |
| Mechanism | Plausible (parent molecule) | Actin-binding domain is the functional core of Tβ4; cell migration, angiogenesis, and anti-inflammatory pathways are well-documented for the parent molecule. Whether the 7-aa fragment reproduces these at comparable magnitude is incompletely resolved. |
Full-Tβ4 clinical track note: RegeneRx's RGN-259 and RGN-137 programs advanced to Phase II human trials using complete 43-aa Tβ4 in topical ophthalmic and wound-gel formulations. These trials involve a different compound and route. They support the Tβ4 family's regenerative biology in human disease contexts but do not establish human efficacy for injectable TB-500 fragment. Every published RCT-grade trial of thymosin beta-4 has used a topical formulation; no published peer-reviewed RCT of injectable systemic Tβ4 or TB-500 in humans exists.
Claim check
| Claim | Verdict | Evidence layer | Confidence |
|---|---|---|---|
| Wound healing, tissue repair, and anti-inflammatory effects | Supported (animal — predominantly full Tβ4; fragment-specific evidence limited) | Animal | Medium — most evidence uses full-length Tβ4, not the 7-aa fragment; fragment-specific controlled data limited |
| TB-500 and thymosin beta-4 are the same or equivalent compound | Contradicted — distinct molecules with different sequences, molecular weights, and pharmacokinetics | In vitro / characterization | High — chemical characterization literature (,) confirms TB-500 is the N-acetylated 17-23 fragment, not the full protein |
| TB-500 improves musculoskeletal injury recovery in humans | Not established — zero controlled human trials for the fragment | None | High confidence in absence — published literature explicitly states no controlled human efficacy or safety trial for TB-500 exists as of 2026 |
| WADA prohibition confirms human performance enhancement | Weak — ban reflects animal evidence of anabolic potential and equine use, not demonstrated human performance effects | Animal | High — source notes WADA added TB-500 in 2011 based on animal evidence and equine sport use; effect size in humans not established |
| TB-500 promotes cancer growth or metastasis | Inconclusive — preclinical Tβ4 correlation with tumor migration; causality not established | In vitro | Medium — Tβ4 elevated in some cancer tissues; mechanistic concern real; no evidence of cancer induction in studies; source describes as correlational, not causative |
Experimental exposure
This section reports exposure used in animal experiments and veterinary contexts. It does not establish human dosing.
| Context | System | Experimental exposure | Duration | Endpoint | Limitation |
|---|---|---|---|---|---|
| Rodent dermal wound healing | Mice and rats (full-thickness wound models) | Full-length Tβ4; dose and route vary by study | Days to weeks | Wound closure rate, collagen deposition, angiogenesis, re-epithelialization | Studies used full-length Tβ4 (43 aa), not the TB-500 fragment; human translation not established |
| Cardiac ischemia model | Adult mice (myocardial infarction model) | Full-length Tβ4 (study-specific dose) | Acute and subacute post-MI timepoints | Cardiomyocyte survival, ejection fraction, fibrosis, progenitor cell activation | Full Tβ4 in animal model; fragment-specific cardiac evidence not individually extracted; human cardiac outcomes not established for either compound |
| Hair follicle stimulation | Mice | Full-length Tβ4 | Study-specific | Hair follicle progenitor cell activation, hair growth initiation | Full Tβ4 in animal model; preliminary area with no human data |
| Equine veterinary use | Racehorses | TB-500 fragment (Medivet veterinary product); dose not specified in source | Recovery periods for musculoskeletal injuries | Musculoskeletal injury recovery (uncontrolled) | Not a controlled experimental study; species differences from human; uncontrolled veterinary application |
No controlled animal experiment specifically evaluating the TB-500 heptapeptide fragment under defined experimental conditions is individually extracted from the available literature. Most animal evidence in the TB-500 literature was conducted with full-length thymosin beta-4.
Preclinical safety signals
| Signal | System | Notes |
|---|---|---|
| No serious adverse events documented | Limited human gray-market community use; preclinical and veterinary use | Source notes clean profile from community reports. Surveillance is informal and not pharmacovigilance data; absence of documented events does not establish safety. |
| Mild injection-site reactions | Human community use; animal models | Occasional soreness or redness at injection site; described as transient in source. |
| Fatigue or lethargy | Human community use | Commonly reported in early use period; described as transient in source. |
| Theoretical oncogenic concern | In vitro and preclinical (full Tβ4) | Tβ4 has documented roles in tumor cell migration, invasion, and metastasis in cancer models. Elevated Tβ4 expression observed in thyroid, hepatocellular, and colorectal cancer tissue. Source states this appears to be a consequence of tumor biology rather than causative, and no studies have demonstrated that TB-500 causes cancer initiation. Mechanistic concern warrants caution in those with active or recent malignancy. |
| Long-term safety | Not established | No chronic human safety data. Gray-market community use does not constitute pharmacovigilance. |
Theoretical interaction concern (source-described): TB-500's pro-angiogenic properties — VEGF upregulation and promotion of cell migration — would be expected to oppose the intended effect of anti-angiogenic oncology and ophthalmology therapies (bevacizumab, aflibercept, VEGF-targeted kinase inhibitors, anti-VEGF intravitreal agents). Source identifies this as a theoretical concern derived from mechanism; no controlled interaction data exists.
Source-described cautions: Pregnancy and breastfeeding — no human data; listed as contraindications in source. Active or recent-history malignancy — mechanistic concern based on Tβ4's role in tumor cell migration. Pediatric use — no studies.
Regulatory status
| Jurisdiction | Status |
|---|---|
| US (FDA) | Not approved. No approved human or veterinary pharmaceutical product. Removed from 503A category 2 (April 22, 2026; nomination withdrawn). FDA intends to consult PCAC July 23, 2026 regarding TB-500 acetate and free-base forms; no compounding authorization pending PCAC outcome. [R5] |
| EU (EMA) | No marketing authorization identified in source. |
| Australia (TGA) | Per available sources, TGA classifies as Schedule 4 prescription-only substance; enforcement actions taken against unapproved peptide sales. |
| Canada / UK (MHRA) | No approved status; unapproved investigational agent per source. |
| WADA | per available sources as prohibited under S2 (Peptide Hormones, Growth Factors, Related Substances and Mimetics) at all times since 2011. Multiple athlete and equine doping sanctions documented. Validated LC-MS doping-control assays for the TB-500 fragment exist (established 2011, Hong Kong Jockey Club Racing Laboratory). Current list status not independently refreshed in this card. [R3, R4] |
| Veterinary | No FDA-approved veterinary pharmaceutical product exists in the US. FEI and multiple racing authorities have banned TB-500 for use in competitive horses following widespread detection of equine use. |
Regulatory status is as reported in the available literature and has not been independently refreshed in this card.
Mechanism
TB-500's proposed mechanism follows from the actin-binding biology of the parent thymosin beta-4. Evidence for the mechanism is derived from studies of the full-length protein and from the conservation of the actin-binding domain in the 7-aa fragment.
Actin sequestration and cytoskeletal regulation: The LKKTETQ sequence is the primary actin-binding domain of Tβ4. By sequestering monomeric G-actin, TB-500 is proposed to regulate the available pool for F-actin polymerization — the cytoskeletal process underlying cell migration, division, and tissue reorganization. Actin-binding activity of the isolated fragment has been characterized in basic research.
Cell migration promotion: Via regulation of cell-surface integrins and matrix metalloproteinases (MMPs), Tβ4 promotes migration of endothelial cells, keratinocytes, and other repair-relevant cell types to sites of injury. This is proposed as the mechanistic basis for wound healing acceleration and is the most consistent finding across model systems.
Angiogenesis via VEGF upregulation: Promotes new blood vessel formation through vascular endothelial growth factor (VEGF) signaling. This mechanism underlies both the proposed therapeutic benefit in wound healing and cardiac repair, and the theoretical concern regarding co-administration with anti-angiogenic therapies.
NF-κB modulation (anti-inflammatory): Suppresses pro-inflammatory cytokine and chemokine production through NF-κB pathway inhibition. Documented in sepsis, encephalomyelitis, and organ inflammation animal models.
Akt/mTOR signaling: Promotes cell survival and proliferation in injury-context models.
Central uncertainty: Whether a 7-amino acid fragment reproduces the 43-aa protein's multifunctional biology is incompletely resolved. The actin-binding motif is retained, but half-life is substantially shorter and tissue distribution and protein-protein interaction capacity differ. published literature explicitly identifies this as the core unresolved mechanistic question for TB-500 specifically.
Chemistry
| Field | Value |
|---|---|
| Sequence | Ac-Leu-Lys-Lys-Thr-Glu-Thr-Gln-OH (Ac-LKKTETQ-OH) |
| Length | 7 amino acids |
| Topology | Linear |
| Modification | N-terminal acetyl group (confers proteolytic stability) |
| Formula | C₄₃H₇₅N₁₃O₁₇ |
| Molecular weight | 889.0 Da (source: RP; for the heptapeptide fragment) |
| CAS | 77591-33-4 |
| Origin | Positions 17–23 of thymosin beta-4 (full 43-aa protein); synthesized as isolated fragment; no natural occurrence as isolated peptide |
| Half-life | Short: minutes to hours in plasma (source-described) |
| Sequence confidence | Verified — consistent across RP and PL sources; fragment identity confirmed in doping-control characterization literature (,) |
Source discrepancy note: The PE source describes TB-500 using parameters corresponding to the full-length thymosin beta-4 parent protein (43 amino acids, 4963 Da). The RP source provides chemistry specific to the TB-500 heptapeptide (7 amino acids, Ac-LKKTETQ-OH, 889.0 Da), consistent with the doping-control characterization literature. RP values are used here. The discrepancy reflects the persistent labeling confusion between "TB-500" and "thymosin beta-4" in source materials and in the commercial supply chain.
Community patterns
This section describes reported off-label community use patterns from the available literature. These patterns are not clinically validated and are not equivalent to label or trial evidence.
| Pattern | Evidence quality | Notes |
|---|---|---|
| Subcutaneous and intramuscular injection for musculoskeletal injury recovery | Anecdotal; source-aggregated community reports (approximately 2,500+ forum and clinic observations per RP source) | Source documents widespread community use for muscle and soft-tissue recovery. No controlled human trial has tested this use case for either TB-500 or injectable full Tβ4. Source-aggregated count is an unverified gray-market observation, not study enrollment data. |
| Pairing with BPC-157 (commonly called "wolverine stack") | Anecdotal; per available sources community and clinic use pattern | Source describes co-administration of TB-500 and BPC-157 as the dominant community protocol. published literature explicitly notes there is no head-to-head controlled data on either compound or the combination, and that the rationale (mechanistic complementarity) is not the same as demonstrated additive benefit. No controlled human study has evaluated the combination. |
Gray-market product identity is a material concern noted in source: research-chemical TB-500 products vary in purity and peptide identity, with documented instances of full Tβ4 substitution or other synthetic fragments being sold as TB-500. Source notes that synthesis complexity of the heptapeptide is a factor in quality variance.
Open questions
- Fragment-versus-parent equivalence: Whether the 7-aa fragment recapitulates the 43-aa Tβ4's biological effects at comparable magnitude is the central unresolved question. The actin-binding motif is preserved, but half-life, tissue distribution, and protein-protein interaction capacity differ substantially between the fragment and the parent protein.
- Human efficacy for the primary use case: The dominant community use — musculoskeletal injury recovery via subcutaneous or intramuscular injection — has never been evaluated in a controlled human trial for either TB-500 or injectable full Tβ4. The entire human clinical track for this family uses topical formulations for ophthalmological and dermal wound indications.
- Human pharmacokinetics: Bioavailability, tissue distribution, and effective half-life of TB-500 after subcutaneous or intramuscular injection have not been rigorously characterized in humans under controlled conditions.
- Cancer safety: Tβ4's documented involvement in tumor cell migration and elevated expression in certain human cancers creates a mechanistic concern. Whether exogenous TB-500 at any dose materially affects cancer risk is not established by the available evidence.
- Long-term systemic safety: No chronic human safety data exists. The absence of documented serious adverse events in gray-market community use reflects informal and limited surveillance, not pharmacovigilance.
- Product identity and purity: Research-chemical TB-500 lacks regulatory quality control. Source documents substitution with full Tβ4 or other fragments. The dose and identity of products reaching users cannot be assumed.
- Regulatory pathway: No pharmaceutical developer is actively pursuing a human clinical IND for the TB-500 heptapeptide fragment specifically. Without a sponsoring program, no human Phase I, dose-ranging, or efficacy trial is currently open for this compound.
Research directions for this peptide, selected from the current sources — hypotheses you can explore and model. None of it is proven yet; tap any one to see the full thinking.
If the acetyl group on the end of TB-500 is removed, would the peptide lose all activity?
If true, manufacturers and regulators would know exactly which chemical form to study, avoiding wasted trials on inactive variants.
If scientists lengthened TB-500 by just a handful of building blocks from the parent protein, could it repair tissue far better without becoming too complex to make?
If this worked, it could bridge the gap between the cheap but unproven fragment and the effective but larger parent, giving drug developers a practical new candidate.
If TB-500 does not stick tightly to actin, could it be acting on other molecules in the body?
If true, researchers would know to look elsewhere for its mechanism, which could reveal new biology or explain side effects before anyone invests in human trials.
If tiny amounts enter the brain, could TB-500 reduce harmful inflammation in diseases like Alzheimer or Parkinson?
If this were possible, it might offer a simpler, cheaper starting point for neuroprotective drug discovery, especially for diseases with few options.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.8706249594688416 | openfold3-mlx |
| ranking score | 0.932434618473053 | openfold3-mlx |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.399 | global PDE — lower = better |
| disorder | 0.103 | fraction disordered |
| chain pair ipTM (A, B) | 0.871 | interface quality |
▸3-letter notation
▸recipeopenfold3-mlx 0.3.1
| parameter | value |
|---|---|
| model | openfold3-mlx 0.3.1 |
| weights | aedd8f3eb814e392… |
| hardware | apple_m4_base_16gb |
| mlx version | 0.31.1 |
| python | 3.14.3 |
| random seed | 42 |
| msa strategy | colabfold |
| diffusion samples | 1 |
| runtime | 293s |
| predicted by | mlx@peptide |
| predicted at | 2026-04-22 |
python3 openfold3/run_openfold.py predict --query_json {query.json} --runner_yaml examples/example_runner_yamls/mlx_runner.yml --output_dir {output_dir} --num_diffusion_samples 1 ▸citationbibtex
@peptide{pep00013,
sequence = {SDKPDMAEIEKFDKSKLKKTETQEKNPLPSKETIEQEKQAGES},
target = {actin},
author = {peptidemodel},
year = {2026},
status = {bioassayed}
}