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TB-500
Research PeptideAlso known as: Thymosin Beta-4 · Thymosin β4 · Tβ4 · TB4 · Timbetasin · Thymosin Beta-4 Fragment (17-23) · Ac-LKKTETQ · TB4-Frag · RGN-137 · RGN-259
Animal Only
"TB-500" refers to either a 7-amino-acid heptapeptide (Ac-LKKTETQ) or full-length 43-residue thymosin beta-4 depending on the product, research peptide vendors typically sell the latter under the former name. Evidence for the compound's claimed benefits is limited to animal models and in-vitro studies: rodent wound-healing and angiogenesis models, mouse cardiac-epicardial-progenitor studies, and cell-culture mechanistic work. The musculoskeletal repair claim dominating the research peptide market has no published controlled research evidence.
Two different compounds are sold as 'TB-500'
"TB-500" historically referred to a 7-amino acid heptapeptide (Ac-LKKTETQ, MW ~809 Da), the compound sold as a veterinary product for horses and greyhounds in the early 2010s. The research peptide market now overwhelmingly sells full-length thymosin beta-4 (43 amino acids, MW ~4,964 Da) under the same "TB-500" label, even though the two are structurally distinct molecules with different pharmacokinetics and activity spectra. The available preclinical literature predominantly covers the full-length protein. Without ESI-MS confirmation on a product COA, you cannot tell which compound is in the vial.
For laboratory research use only. Not for human or animal consumption.
Evidence Tier
Animal Only
Mol. Weight
4963.5 Da
Last Reviewed
Apr 20, 2026
Claimed benefits by evidence tier
Column header colour matches the tier
Animal Only4
- Accelerates soft-tissue injury repair (tendon, ligament, muscle)
- Reduces scar formation
- Promotes hair growth
- Neuroprotection / stroke recovery
Anecdotal1
- General athletic performance enhancement
Unsupported1
- Anti-aging / longevity
About this peptide
Plain English
The human body produces a protein called thymosin beta-4 in almost every cell, and when tissues are injured, this protein helps orchestrate the repair process, it encourages cells to migrate into the damaged area, promotes the growth of new blood vessels, and damps down inflammation. "TB-500" is the name given to either a fragment of that protein (a 7-amino-acid piece) or the full protein itself, depending on which product you are looking at. Research into thymosin beta-4 spans decades of animal and in vitro studies, with more recent preclinical investigation across wound healing and related areas. The compound sold in research peptide markets is not an approved medicine and is labeled for research use only.
Technical
Thymosin beta-4 (Tβ4) is a 43-residue, N-terminally acetylated polypeptide constitutively expressed at high concentrations in the cytosol of most mammalian cell types. Its primary structural feature, the conserved LKKTET motif at residues 17–22, confers high-affinity binding to monomeric G-actin (Kd ~0.5–0.7 μM), making Tβ4 the principal G-actin sequestering protein in many tissues. Beyond actin regulation, Tβ4 modulates NF-κB, VEGF, and ILK/AKT signaling, producing pleiotropic effects on cell migration, angiogenesis, stem-cell mobilization, and inflammation suppression. The synthetic heptapeptide TB-500 (Ac-LKKTETQ, residues 17–23) retains the core actin-binding domain and has been shown to independently promote angiogenesis and cell migration in vitro and in animal models, though its activity spectrum differs from full-length Tβ4. Preclinical development of full-length Tβ4 (under INN timbetasin) has been investigated primarily by RegeneRx Biopharmaceuticals across wound-healing (RGN-137 topical gel), ophthalmic (RGN-259 eye drops), and cardiovascular indications; no formulation has achieved regulatory approval in any jurisdiction.
Mechanism of action
G-actin sequestration / cytoskeletal regulation
Tβ4 binds monomeric G-actin with high affinity via the LKKTET motif, sequestering it from polymerization into F-actin. The resulting shift in G-actin/F-actin ratio affects lamellipodium formation, cell polarity, and directional migration. The LKKTETQ sequence must adopt a non-helical conformation to bind actin.
Angiogenesis via VEGF upregulation
Tβ4 upregulates VEGF expression in endothelial cells and promotes endothelial differentiation, migration, and tube formation. In animal models, Tβ4 administration increases blood-vessel density at wound sites. The angiogenic effect is preserved in the heptapeptide fragment (LKKTETQ), indicating the actin-binding domain itself drives this activity.
Anti-inflammatory / NF-κB suppression
Tβ4 downregulates NF-κB signaling and reduces pro-inflammatory cytokine production (TNF-α, IL-1β, IL-6) in macrophages and other immune cells. In animal wound models, Tβ4 application reduces inflammatory infiltrate and shifts the microenvironment toward repair.
Cardiac progenitor cell mobilization / ILK-AKT survival signaling
In rodent myocardial infarction models, Tβ4 activates quiescent epicardial progenitor cells, induces their migration into the myocardium, and promotes differentiation into cardiomyocytes and smooth muscle. Tβ4 also activates ILK and AKT survival signaling, reducing post-ischemic cardiomyocyte apoptosis. An observational study (REGENERATIVE-IHD) noted elevated endogenous Tβ4 in responders to a separate stem-cell intervention; exogenous Tβ4 was not administered.
The majority of mechanistic evidence derives from cell-culture systems and rodent models. Rodent wound-healing, angiogenesis, and cardiac-repair models do not reliably predict outcomes in other species. Extrapolating from rodent cardiac repair (which involves epicardial activation not well-characterized in adult mammals generally) to claims of cardiac regeneration is speculative. Additionally, the available preclinical data predominantly uses full-length Tβ4; whether the heptapeptide TB-500 activates the same pathways is unconfirmed.
Key studies
The actin binding site on thymosin beta4 promotes angiogenesis (2003)
Dominguez JN, de la Rosa A, Navarro F et al. · FASEB Journal
- Participants
- In vitro endothelial cells; mouse matrigel angiogenesis model
- Methodology
- Cell-culture migration assay; Matrigel tube-formation assay; mouse dorsal-sac angiogenesis model. Used full-length Tβ4 and truncated peptide fragments.
- Result
- The heptapeptide Ac-LKKTETQ (TB-500) independently promotes angiogenesis and endothelial cell migration; deletion mutants that cannot bind actin lose angiogenic activity. Establishes that TB-500 (the heptapeptide) has independent biological activity.
Honest read
Key mechanistic study confirming the heptapeptide has real biological activity, not just the full-length protein. However, all data is in vitro/animal, does not establish clinical efficacy of the heptapeptide in humans.
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 (2012)
Teale P et al. · Journal of Chromatography A
- Participants
- Equine (horses, in vivo dosing study)
- Methodology
- Horses given TB-500 (heptapeptide); urine and plasma sampled; LC-MS/MS method developed for detection.
- Result
- Validated LC-MS/MS method capable of detecting TB-500 (Ac-LKKTETQ) in equine urine and plasma. Detection window established.
Honest read
This study confirms (a) TB-500 the heptapeptide was a commercially available product administered to horses, (b) the compound is detectable by mass spec, and (c) doping in equine sport was sufficiently widespread to merit a dedicated analytical method paper. This is not efficacy evidence.
Role of thymosin beta4 in tumor metastasis and angiogenesis (2003)
Goldstein AL, Hannappel E, Sosne G, Bhatt DL et al. (editorial review context; original paper Sharp et al.) · Journal of the National Cancer Institute 95(22):1674
- Participants
- B16-F10 melanoma mouse xenograft model
- Methodology
- B16-F10 melanoma cells transfected to overexpress Tβ4; tumor growth and metastatic lung nodules compared to controls.
- Result
- Tβ4 overexpression significantly increased tumor size, number of metastatic lung nodules, and blood-vessel density in solid tumors (4.4-fold increase in vessels). VEGF upregulation identified as key mediator.
Honest read
This is the primary animal-model evidence for the cancer-growth concern associated with Tβ4's pro-angiogenic mechanism. Important limitations: overexpression model (forced supraphysiological levels) ≠ exogenous peptide administration; mouse xenograft ≠ human oncology; this specific risk has not been studied in human TB-500 users or clinical trials. The finding does not mean administered TB-500 causes cancer, it means the biological mechanism has a plausible oncological risk that has not been adequately evaluated.
Research timeline
- 1965
Thymosin fraction isolated from bovine thymus by Goldstein, White et al. at Albert Einstein College of Medicine. Heterogeneous initial fractions.
- 1981
Thymosin beta-4 identified and sequenced as a distinct 43-amino acid peptide (Low et al.).
- 1991
Safer & Bhatt (Science) identify Tβ4 as the principal G-actin sequestering protein in mammalian cells.
- 1999
Malinda et al. demonstrate Tβ4 accelerates wound healing in corneal and dermal animal models.
- 2003
First documented cancer-concern signal: Goldstein group editorial on Tβ4 overexpression driving tumor growth and metastasis in B16-F10 mouse xenografts (JNCI).
- 2003
Dominguez et al. (FASEB J) show the heptapeptide Ac-LKKTETQ independently promotes angiogenesis, basis for marketing the fragment as biologically active.
- 2004
Crystal structure of the Tβ4–G-actin complex solved (Irobi et al.).
- 2007
European preclinical-to-clinical study of topical RGN-137 gel in venous-stasis and pressure ulcers published (n=72). Early sponsored trial data for Tβ4 topical application.
- 2009
RegeneRx reports sponsored trial results for topical RGN-137 in venous-stasis ulcers (72 subjects). Mid-dose most active in the study.
- 2010
Ruff et al. sponsored IV safety study published, evaluating single and multiple IV doses of full-length Tβ4.
- 2010
Smart/Riley/Bhatt groups publish cardiac-epicardial-progenitor rodent studies, beginning of the cardiovascular research pipeline.
- 2011
Thymosin beta-4 and derivatives (including TB-500) added to the prohibited list under S2, based on equine doping market prevalence and plausible performance-enhancing mechanism from preclinical data.
- 2012
Teale et al. publish equine LC-MS doping-control method for TB-500 (Ac-LKKTETQ). Confirms the compound was widely administered to racehorses and greyhounds.
- 2012
Full peer-reviewed publication of the RGN-137 topical dermal healing study data (Goldstein & Bhatt).
- 2015
REGENERATIVE-IHD observational study reports correlative finding: endogenous Tβ4 elevated in responders. Observational only; exogenous Tβ4 was not administered.
- 2021
Wang et al. publish an independent (non-RegeneRx) IV safety study of recombinant human Tβ4, evaluating a range of IV doses.
- 2023
SEER-1 ophthalmic study results published (RGN-259, n=18). Primary endpoint missed (p=0.0656); secondary endpoint met (p=0.0359). Subsequent studies enrolling.
- 2024
Thymosin beta-4 / TB-500 placed on a regulatory interim list for compounding substances, citing immunogenicity concerns and insufficient safety data.
- 2026
April 16, 2026: Federal Register notice of an advisory committee meeting scheduled for July 23–24, 2026, to review TB-500 / Thymosin Beta-4 among seven peptides. Outcome may affect compounding classification.
What we don't know
- Pharmacokinetics of the heptapeptide TB-500 (Ac-LKKTETQ): all published PK is for full-length Tβ4. The two molecules have MW ~809 vs ~4,964 Da, with different absorption, distribution, and clearance profiles.
- Subcutaneous and intramuscular bioavailability: published IV safety studies used intravenous administration, but the research peptide market overwhelmingly uses subcutaneous injection. SC Tmax, Cmax, and duration are unestablished.
- Long-term safety: the longest published controlled exposure is 14 days IV (Ruff 2010). No long-term safety data at any dose or route.
- Immunogenicity: regulatory concerns have been cited about immunogenicity. No published anti-Tβ4 antibody induction studies; cross-reactivity with endogenous Tβ4 is uncharacterized.
- Cancer risk: the pro-angiogenic mechanism has a plausible tumor-promotion pathway confirmed in mouse overexpression models. No epidemiological or controlled data on cancer incidence with exogenous Tβ4 or TB-500.
- Efficacy for musculoskeletal injuries (tendon, ligament, muscle): the primary use case in the research peptide market. No published controlled research for any orthopedic or sports-injury indication.
- Optimal administration parameters for any indication: even in wound healing, sponsored study data suggests a non-monotonic dose-response, but definitive parameters are unresolved.
- Compound interactions: no published studies with NSAIDs, corticosteroids, immunosuppressants, anticoagulants, or growth factors.
- Whether the heptapeptide and full-length Tβ4 are therapeutically interchangeable: most vendors sell them under the same "TB-500" label; they are structurally different compounds with different MWs and activity spectra.
- Oral bioavailability: not established. Peptides of this size are generally not orally bioavailable without specific formulation technology, but neither compound has been formally studied orally.
Stability & handling
- Lyophilized shelf life
- Up to 24 months at −20°C; up to 36 months at −80°C (vendor consensus; no peer-reviewed TB-500 stability study identified)
- Lyophilized storage
- −20°C routine; −80°C preferred for long-term; amber or foil-wrapped vials to protect Met6 from photo-oxidation
- Reconstitution diluents
- Bacteriostatic water (0.9% benzyl alcohol), preferred for multi-use research aliquoting, Sterile water for injection, single-use, Acetic acid 0.1–1%, improves solubility for some peptide batches
- Reconstituted (refrigerated)
- 28–42 days at 2–8°C (vendor literature; no published analytical stability validation specific to TB-500)
- Reconstituted (room temp)
- Avoid; degradation expected within hours to 1–2 days at ambient temperature
- OK to refreeze
- No
- Light sensitive
- Yes, protect from light
Moderate-to-high light-sensitivity concern: the methionine residue at position 6 (Met6) of full-length Tβ4 is susceptible to photo-oxidation to Met-sulfoxide, more UV-sensitive than most research peptides. Store in amber vials or foil-wrapped. Aggregation / insoluble particulates are a real concern at higher concentrations, reconstitute by gentle swirling rather than vortexing, and visually inspect for turbidity or particulates before use. Reconstitution-volume accuracy matters at common research-market vial sizes (5 mg, 10 mg in 1–2 mL); pipetting errors are a leading real-world potency issue.
Frequently asked questions
What's the difference between TB-500, TB4, and thymosin beta-4?
Thymosin beta-4 (TB4 or Tβ4) is a 43-amino acid protein naturally made in mammalian cells. "TB-500" originally referred specifically to a synthetic 7-amino acid fragment (Ac-LKKTETQ) of that protein, sold as a veterinary product for horses. Today, most research peptide vendors sell the full 43-amino acid thymosin beta-4 under the "TB-500" brand name, making the labels effectively interchangeable in the market despite being structurally different compounds with different molecular weights (~809 vs ~4,964 Da). The published research on both compounds is predominantly in animal and in vitro models. If you are buying "TB-500," request mass-spectrometry confirmation of which compound you actually have.
Does TB-500 have regulatory approval anywhere?
No form of thymosin beta-4 or TB-500 has achieved regulatory approval as a drug in any major jurisdiction. An advisory committee review is scheduled for July 23–24, 2026, to assess the compound's standing on a compounding substances interim list. The compound is sold in research peptide markets labeled for research use only and is not an approved medicine.
Is TB-500 detectable in a sports doping test?
Thymosin beta-4 and TB-500 are prohibited in sport under the S2 category, and validated LC-MS detection methods exist for both the heptapeptide and full-length Tβ4 in urine and plasma. Equine sports methods were published in 2012; anti-doping methods are maintained by accredited laboratories. The compound should be considered detectable and prohibited in any sport that follows this prohibited list.
What does the "research use only" label mean legally?
In most jurisdictions, very little. The label defers potential enforcement in some markets but does not create a legal right to purchase, use, or administer the compound as a therapeutic. In some countries, possession without authorization is an offense regardless of label. The label is a vendor legal strategy, not a recognized regulatory category.
What is the "Wolverine Stack" and is there evidence for it?
The "Wolverine Stack" refers to co-administration of BPC-157 and TB-500, a practice popular in performance and recovery communities. There is no published controlled evidence for this combination. No pharmacokinetic interaction studies exist. No safety data for the combination exists. The theoretical rationale (both have wound-healing properties via different mechanisms) is mechanistically plausible in preclinical models but entirely unsupported by controlled data. The combination label is a marketing construct.
Why was TB-500 originally developed for horses?
TB-500 the heptapeptide was commercially developed and marketed as a veterinary product for racehorses and greyhounds in the early 2010s, promoted as a recovery and performance aid. It entered research peptide markets from the equine market, not through clinical development. This origin matters because: (a) the original compound was the heptapeptide, not full-length Tβ4; (b) the compound had no controlled research data when it entered those markets; (c) it was added to the prohibited list in 2011 based on equine doping prevalence, not established performance effects. Subsequent Tβ4 interest from wound-healing researchers provided a different, and more scientifically grounded, preclinical development path for the full-length molecule.
Last researched: Apr 20, 2026
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