TB-500 is a synthetic N-acetylated heptapeptide fragment, commonly described as Ac-LKKTETQ, that corresponds to residues 17–23 of full-length thymosin beta-4, while human research has mainly studied full-length thymosin beta-4 formulations rather than TB-500 itself (Research) (FDA).
TB-500 is often discussed in peptide communities because it is linked conceptually to thymosin beta-4, an endogenous 43–amino-acid actin-binding peptide studied in wound, corneal, cardiovascular, and tissue-repair research (Review). The direct human evidence base for administered TB-500 is extremely limited because FDA staff reported that they did not identify published human clinical or human pharmacokinetic studies in which TB-500 itself was administered to patients or healthy volunteers (FDA). Human findings therefore come mostly from molecule-distinct full-length thymosin beta-4 formulations, including topical gel, ophthalmic RGN-259, and intravenous thymosin beta-4 or recombinant human thymosin beta-4 (Research) (Research). TB-500 is also commonly paired online with BPC-157 under the informal name “Wolverine stack,” but that nickname reflects peptide-community use and marketing language rather than a validated human clinical protocol (Reuters).
Ingredient Identity
- Official name(s): TB-500; thymosin beta-4 fragment LKKTETQ; N-acetyl-LKKTETQ (FDA).
- Synonyms: TB500, TB-500 acetate, TB-500 free base, thymosin beta-4 fragment 17–23, Ac-LKKTETQ (Research).
- Classification: Synthetic peptide fragment related to the actin-binding region of full-length thymosin beta-4 (FDA).
- CAS number: A single universally reliable CAS number was not confirmed from the locked evidence set, and regulatory materials identify the substance primarily by sequence and salt/free-base status rather than by CAS number (FDA).
- Endogenous vs exogenous: TB-500 is an exogenous synthetic fragment, whereas full-length thymosin beta-4 is an endogenous peptide present in mammalian cells and body fluids (Review).
Ingredient Snapshot
- Classification: TB-500 is a synthetic N-acetylated peptide fragment derived from the thymosin beta-4 sequence, not full-length thymosin beta-4 itself (FDA).
- Endogenous vs exogenous status: TB-500 is not described as an endogenous full-length human peptide, while thymosin beta-4 is a naturally occurring 43–amino-acid peptide found broadly in mammalian tissues (Review).
- Primary human research domains: Published human research has focused mainly on full-length thymosin beta-4 formulations in venous ulcers, pressure ulcers, dry eye, neurotrophic keratopathy, corneal epithelial defects, and early cardiovascular research (Research) (Research).
- Common study formats: Human studies include randomized controlled ophthalmic trials, topical wound-healing trials, IV phase I safety/PK studies, and trial registrations for wound and cardiovascular indications (Research) (Research).
- Pharmacokinetic characterization status: FDA staff reported no published human PK studies of administered TB-500, while animal and in-vitro work suggests TB-500 can be metabolized into shorter peptide fragments (FDA) (Research).
- Regulatory context (U.S./EU): FDA lists thymosin beta-4 fragment LKKTETQ, also known as TB-500, among bulk drug substances that may present significant safety risks in compounding, and an EU trial registry documents clinical-trial activity for thymosin beta-4 gel rather than broad EU approval for TB-500 (FDA) (EU CTR).
- Evidence maturity: The evidence maturity for TB-500 itself is emerging and limited, because direct administered-human TB-500 studies were not identified by FDA, while indirect full-length thymosin beta-4 studies provide only molecule-adjacent context (FDA).
Introduction
TB-500 is commonly used online as a name for a synthetic peptide fragment corresponding to the N-acetylated 17–23 region of human thymosin beta-4, with the sequence Ac-LKKTETQ (Research). Full-length thymosin beta-4 is a naturally occurring 43–amino-acid peptide that binds actin, a structural protein involved in cell shape and movement, but TB-500 is a shorter synthetic fragment rather than the full endogenous molecule (Review).
People often look up TB-500 because peptide communities discuss it for tissue-repair, injury-recovery, tendon, muscle, and wound-healing contexts, and recent reporting has described BPC-157 plus TB-500 as a popular informal pairing called the “Wolverine stack” (Reuters). The scientific evidence behind those discussions is uneven, because direct human TB-500 studies are lacking, while human research has more often examined full-length thymosin beta-4 formulations in skin wounds, corneal disorders, and early cardiovascular settings (FDA) (Research).
This article is informational only, describes TB-500 as a biochemical substance studied directly and indirectly in research contexts, and does not provide medical or dosing advice.
Quick Summary
- TB-500 is best defined as a synthetic Ac-LKKTETQ fragment related to thymosin beta-4, not as full-length thymosin beta-4 itself (Research) (FDA).
- FDA staff reported that they did not identify published clinical studies in which TB-500 itself was administered to humans for any disease or condition (FDA).
- The strongest human evidence adjacent to TB-500 comes from full-length thymosin beta-4 formulations studied in Eye Health and Beauty and Skin Health, especially corneal disorders and wound-healing trials (Research) (Research).
- Direct TB-500 pharmacokinetic evidence is mainly non-human or in-vitro, including horse and rat research showing systemic detection and metabolism into shorter peptide fragments (Research) (Research).
- TB-500 is discussed in peptide communities and is often paired with BPC-157 as the “Wolverine stack,” but this community term is not evidence that the combination has been validated in controlled human trials (Reuters).
- FDA identifies compounded drugs containing thymosin beta-4 fragment LKKTETQ as potentially posing immunogenicity and peptide-impurity risks, and FDA states that human exposure data for drug products containing the fragment were not identified (FDA).
- Non-human studies can help explain why TB-500 attracts attention, but animal, cell, and analytical studies cannot substitute for direct human safety or efficacy data (FDA) (Research).
Human Research Findings by Condition
Beauty and Skin Health
Human research adjacent to TB-500 has included topical full-length thymosin beta-4 studies in venous ulcers, pressure ulcers, and epidermolysis bullosa wound contexts, but these studies do not administer the TB-500 fragment itself (Research) (ClinicalTrials.gov). The overall signal is exploratory: some studies reported wound-healing signals, while the evidence remains limited by formulation differences, small study programs, and molecule mismatch between full-length thymosin beta-4 and TB-500 (Research).
Key human study
Dose studied: 0.03% topical thymosin beta-4 gel
Population: Patients with venous ulcers
Duration: Up to approximately 3 months
Researchers evaluated topical full-length thymosin beta-4 in venous ulcers and reported that the 0.03% dose appeared to show a potential accelerated-healing signal in a phase 2 context (Research). This study is relevant to TB-500 only indirectly because it used full-length thymosin beta-4 rather than the Ac-LKKTETQ fragment (FDA).
Result: Human clinical study reported a modest improvement
Evidence strength: Limited
Study source: (Research)
Additional human study
Dose studied: 0.01%, 0.02%, and 0.1% topical thymosin beta-4 gel
Population: Patients with pressure ulcers
Duration: Registered phase 2 treatment period
A registered phase 2 study evaluated multiple topical thymosin beta-4 gel concentrations in pressure-ulcer patients and included safety and wound-healing outcomes (ClinicalTrials.gov). The registry supports trial design and exposure context, but it does not convert the findings into direct TB-500 evidence because the registered investigational product was thymosin beta-4 gel (ClinicalTrials.gov).
Result: Human clinical studies reported mixed findings
Evidence strength: Emerging
Study source: (ClinicalTrials.gov)
Eye Health
Eye Health is the most developed human research area adjacent to TB-500, but the studies used ophthalmic full-length thymosin beta-4 formulations such as RGN-259 rather than TB-500 itself (Research) (Research). Human evidence includes neurotrophic keratopathy, chronic corneal epithelial defects, diabetic corneal wounds, and dry eye studies, with stronger evidence for ophthalmic research than for systemic TB-500 use (Research).
Key human study
Dose studied: 0.1% RGN-259 ophthalmic solution
Population: Patients with stages 2 and 3 neurotrophic keratopathy
Duration: Phase 3 randomized treatment period
A randomized, placebo-controlled, double-masked phase 3 trial evaluated 0.1% RGN-259 ophthalmic solution for persistent epithelial defects in neurotrophic keratopathy (Research). The PubMed record reports a healing and comfort signal with no significant adverse effects, but the formulation was ophthalmic thymosin beta-4 and not TB-500 (Research).
Result: Randomized human trial reported a statistically significant improvement
Evidence strength: Moderate
Study source: (Research)
Additional human study
Dose studied: 0.1% thymosin beta-4 ophthalmic solution twice daily
Population: Subjects with moderate to severe dry eye
Duration: 28 days
A randomized, placebo-controlled phase 2 study using a controlled adverse environment model evaluated 0.1% thymosin beta-4 ophthalmic solution in dry eye (Research). The trial reported selected improvements in signs and symptoms, but this remains indirect evidence for TB-500 because the study substance was ophthalmic full-length thymosin beta-4 (Research).
Result: Randomized human trial reported a statistically significant improvement
Evidence strength: Moderate
Study source: (Research)
Cardiovascular Health
Cardiovascular Health research has included early-stage human work with full-length thymosin beta-4 or thymosin beta-4–pretreated cell therapy, but the evidence does not establish direct TB-500 cardiovascular effects in humans (ClinicalTrials.gov) (Research). The cardiovascular evidence is best described as exploratory and molecule-adjacent because FDA did not identify published clinical studies administering TB-500 itself (FDA).
Key human study
Dose studied: 450 mg or 1200 mg injectable RGN-352 thymosin beta-4
Population: Patients with acute myocardial infarction undergoing PCI
Duration: Registered clinical-trial treatment and follow-up period
A registered trial evaluated injectable RGN-352, a thymosin beta-4 formulation, in acute myocardial infarction patients undergoing percutaneous coronary intervention (ClinicalTrials.gov). This source supports trial design and exposure context, but it should not be interpreted as direct evidence for TB-500 because RGN-352 is not the same as the TB-500 fragment (FDA).
Result: Human evidence remains limited or inconclusive
Evidence strength: Emerging
Study source: (ClinicalTrials.gov)
Additional human study
Dose studied: Endothelial progenitor cells pretreated with thymosin beta-4 for 24 hours
Population: STEMI patients
Duration: Pilot follow-up period
A small randomized pilot study evaluated endothelial progenitor cells pretreated with thymosin beta-4 in patients with ST-elevation myocardial infarction (Research). The design makes this an indirect cardiovascular-repair context rather than evidence that systemic TB-500 improves cardiovascular outcomes (Research).
Result: Human clinical study reported a modest improvement
Evidence strength: Emerging
Study source: (Research)
Muscle Health
Muscle Health is a major reason TB-500 is discussed in peptide communities, but direct human TB-500 trials for muscle injury, athletic recovery, or muscle growth were not identified by FDA (FDA). Non-human thymosin beta-4 studies and community narratives may explain interest in this area, but they do not establish human efficacy or safety for TB-500 (Review).
Key human study
Dose studied: No direct administered-human TB-500 dose identified
Population: No direct human TB-500 muscle-health study population identified
Duration: Not applicable
FDA staff reported that they did not find published information in which TB-500 was administered to patients to treat any disease or condition (FDA). This means claims about TB-500 for muscle recovery rely on extrapolation from non-human, in-vitro, or full-length thymosin beta-4 evidence rather than direct human trials (FDA).
Result: Human evidence remains limited or inconclusive
Evidence strength: Inconclusive
Study source: (FDA)
Additional human study
Dose studied: No direct human TB-500 dose identified
Population: Peptide-community users are discussed in reporting, not in controlled clinical studies
Duration: Not applicable
Reuters reported that BPC-157 and TB-500 have become increasingly popular and that their combination is popularly known as the “Wolverine stack,” but this reporting describes popularity and claimed use rather than controlled human evidence (Reuters). The same article noted FDA officials urging human clinical trials for the peptides under review, which supports a cautious interpretation of community use claims (Reuters).
Result: Human evidence remains limited or inconclusive
Evidence strength: Inconclusive
Study source: (Reuters)
Joint Health
Joint Health and tendon-repair discussions around TB-500 are driven mainly by non-human studies and peptide-community use rather than direct human TB-500 clinical trials (FDA) (Research). The most relevant direct TB-500 combination evidence identified for this context is a rat Achilles tendon study, which is useful for mechanistic orientation but cannot establish human outcomes (Research).
Key human study
Dose studied: No direct administered-human TB-500 joint-health dose identified
Population: No direct human TB-500 tendon or joint-injury population identified
Duration: Not applicable
FDA’s TB-500 review stated that the nominator proposed “wound healing” but did not provide clinical evidence for TB-500, and FDA did not find published clinical information in which TB-500 was administered to patients for any disease or condition (FDA). This makes human Joint Health evidence for TB-500 indirect and currently unsupported by direct clinical trials (FDA).
Result: Human evidence remains limited or inconclusive
Evidence strength: Inconclusive
Study source: (FDA)
Additional human study
Dose studied: Not a human dose; rat Achilles tendon injury model
Population: Rats with Achilles tendon injury
Duration: Animal-study treatment and healing period
A 2026 rat study evaluated BPC-157, synthetic thymosin beta-4/TB-500, and their combination in Achilles tendon healing using biomechanical, histopathological, histochemical, and immunohistochemical analyses (Research). This study is relevant for understanding why the BPC-157 plus TB-500 pairing attracts interest, but it remains non-human evidence and should not be treated as a clinical protocol (Research).
Result: Evidence currently comes mainly from animal or experimental research
Evidence strength: Emerging
Study source: (Research)
Dosage & Study Snapshot (Research Context)
Human exposure data for TB-500 itself are not available in the locked evidence set, so this section reports exposures studied for endogenous thymosin beta-4, full-length thymosin beta-4 formulations, and non-human TB-500 PK where relevant (FDA). These ranges are research exposures only, not dosage guidance, and they should not be interpreted as recommended, safe, or effective amounts for human use (FDA).
Endogenous wound-fluid thymosin beta-4 up to approximately 20 mg/L:
A human wound-fluid study measured thymosin beta-4 after abdominal surgery and reported measurable concentrations that declined over time (Research). This is not an administered dose; it is an endogenous exposure marker showing that full-length thymosin beta-4 is present in wound environments (Research). The finding matters because it helps explain why thymosin beta-4 became a wound-repair research target, but it does not establish that TB-500 administration reproduces the same biology (FDA). This exposure belongs before administered topical or injectable bands because it represents the lowest direct human-context evidence in the locked library.
Result: Observational association
Evidence strength: Observational
Notes / limitations: Endogenous wound-fluid measurement is not equivalent to dosing TB-500.
Serum immunoreactive thymosin beta-4 measured in healthy adults:
A human ELISA study measured thymosin beta-4 in serum from 681 healthy adults, providing a circulating endogenous context rather than an administered exposure study (Research). This kind of study helps identify natural human presence of thymosin beta-4–related immunoreactivity, but it does not show the safety or efficacy of TB-500 (Research). It also cannot determine whether synthetic TB-500 behaves like endogenous full-length thymosin beta-4 in tissues (FDA). The band is included to separate endogenous human measurement from intervention dosing.
Result: Observational association
Evidence strength: Observational
Notes / limitations: Serum measurement does not define a therapeutic exposure.
0.01% topical thymosin beta-4 gel:
A registered venous-stasis-ulcer trial included a 0.01% topical thymosin beta-4 gel arm given once daily for up to 84 days (ClinicalTrials.gov). This formulation was topical full-length thymosin beta-4 gel, not TB-500, so it belongs in the indirect human evidence category (ClinicalTrials.gov). The population was patients with venous stasis ulcers, and the outcomes focused on wound closure and safety endpoints (ClinicalTrials.gov). It provides low-concentration topical context but does not support systemic peptide-community dosing claims.
Result: Mixed findings
Evidence strength: Emerging
Notes / limitations: The trial context is topical wound research, not injectable TB-500 use.
0.03% topical thymosin beta-4 gel:
A phase 2 venous-ulcer study reported that 0.03% topical thymosin beta-4 appeared to have potential to accelerate wound healing in some patients (Research). The study population had venous ulcers, and the intervention was a topical full-length thymosin beta-4 gel formulation (Research). The result is relevant to Beauty and Skin Health but only indirectly relevant to TB-500 because TB-500 is a shorter fragment (FDA). This band is distinct from the 0.01% and 0.1% topical concentrations because the published signal was specifically associated with 0.03%.
Result: Modest improvement
Evidence strength: Limited
Notes / limitations: The study does not establish TB-500 fragment effects.
0.1% topical thymosin beta-4 gel:
A registered venous-stasis-ulcer trial included a 0.1% topical thymosin beta-4 gel arm in addition to lower topical concentrations (ClinicalTrials.gov). This exposure was studied in a wound-healing context using topical full-length thymosin beta-4 rather than TB-500 (ClinicalTrials.gov). The dose band helps show that human topical wound research tested multiple concentrations, but it does not provide a systemic dose basis for TB-500 (FDA). The higher topical concentration should therefore be interpreted as formulation-specific clinical-trial context.
Result: Mixed findings
Evidence strength: Emerging
Notes / limitations: Percent gel exposures cannot be converted into injectable TB-500 dosing.
0.1% ophthalmic thymosin beta-4 solution:
Ophthalmic human studies evaluated 0.1% RGN-259 or thymosin beta-4 eye drops in neurotrophic keratopathy and dry eye research (Research) (Research). These studies used local ocular delivery, which is materially different from systemic or injectable peptide use (Research). Reported outcomes included corneal epithelial healing, ocular comfort, and dry-eye signs or symptoms in specific trial settings (Research). The band is relevant for Eye Health evidence but not for determining a TB-500 systemic dose.
Result: Statistically significant improvement
Evidence strength: Moderate
Notes / limitations: Ophthalmic thymosin beta-4 is not the same exposure context as TB-500 injections.
0.05–25.0 μg/kg IV recombinant human thymosin beta-4:
A first-in-human phase I study evaluated single IV recombinant human thymosin beta-4 doses of 0.05, 0.25, 0.5, 2.0, 5.0, 12.5, and 25.0 μg/kg in healthy Chinese volunteers (Research). The study examined safety, tolerability, pharmacokinetics, and anti-drug antibodies, which makes it useful for full-length thymosin beta-4 characterization (Research). It does not establish human PK for TB-500 because the administered molecule was recombinant human thymosin beta-4, not the Ac-LKKTETQ fragment (FDA). This band is useful because it shows that some human IV PK work exists for full-length thymosin beta-4.
Result: Neutral overall findings
Evidence strength: Limited
Notes / limitations: Full-length recombinant thymosin beta-4 PK cannot be assumed to apply to TB-500.
0.5–5.0 μg/kg/day IV recombinant human thymosin beta-4 for 10 days:
The same first-in-human study also evaluated multiple daily IV doses of recombinant human thymosin beta-4 at 0.5, 2.0, and 5.0 μg/kg/day for 10 days (Research). The trial monitored safety, tolerability, pharmacokinetics, and anti-drug antibody outcomes in healthy volunteers (Research). This repeated-dose design provides controlled human exposure data for recombinant full-length thymosin beta-4, not TB-500 (FDA). It should be read as a phase I characterization study rather than as efficacy evidence.
Result: Neutral overall findings
Evidence strength: Limited
Notes / limitations: Repeated-dose tolerability in healthy volunteers does not establish disease-treatment effects.
42–1260 mg IV synthetic thymosin beta-4:
A randomized, placebo-controlled phase I study evaluated single and repeated IV synthetic thymosin beta-4 doses, including 42, 140, 420, and 1260 mg in healthy volunteers (Research). The study examined safety and pharmacokinetics and reported no serious adverse events or dose-limiting toxicities in the PubMed abstract (Research). This is a full-length thymosin beta-4 exposure context and should not be treated as a TB-500 dose band (FDA). It remains important because it is one of the clearer controlled human systemic thymosin beta-4 studies.
Result: Neutral overall findings
Evidence strength: Limited
Notes / limitations: The molecular mismatch is central: IV thymosin beta-4 is not TB-500.
10 mg subcutaneous TB-500 in horses:
A horse doping-control study identified TB-500 and metabolites in equine plasma and urine after TB-500 administration, and FDA summarized horse data showing plasma concentrations peaking about 1–2 hours after subcutaneous administration and becoming unquantifiable between about 6 and 10 hours (Research) (FDA). This is the most directly relevant PK-style exposure evidence for TB-500, but it is non-human and cannot define human PK or safety (FDA). The evidence is relevant to detection, metabolism, and anti-doping context rather than therapeutic use (Research). It should be treated as animal pharmacokinetic context only.
Result: Preliminary signal
Evidence strength: Emerging
Notes / limitations: Horse PK does not predict human safety, efficacy, or dosing.
Key Takeaways from Human Research
- Direct human clinical evidence for administered TB-500 was not identified by FDA, so the evidence base must be interpreted as indirect and incomplete (FDA).
- Eye Health has the most developed molecule-adjacent human research because ophthalmic thymosin beta-4 studies include randomized trials in dry eye and neurotrophic keratopathy (Research) (Research).
- Beauty and Skin Health evidence includes topical full-length thymosin beta-4 wound studies, but these findings do not prove TB-500 fragment effects (Research) (FDA).
- Cardiovascular Health evidence is exploratory and includes registered injectable thymosin beta-4 research and thymosin beta-4–pretreated cell-therapy research rather than direct TB-500 trials (ClinicalTrials.gov) (Research).
- Muscle Health and Joint Health claims around TB-500 are more visible in peptide communities than in direct human trials, and the “Wolverine stack” is an informal pairing rather than a validated clinical combination (Reuters).
- FDA safety concerns include possible immunogenicity, aggregation, peptide-related impurities, and absence of identified human exposure data for drug products containing thymosin beta-4 fragment LKKTETQ (FDA).
Origin & Natural Occurrence
TB-500 is a synthetic peptide fragment, and analytical work identified the substance in a product called TB-500 as the N-terminal acetylated 17–23 fragment of human thymosin beta-4, Ac-LKKTETQ (Research). Full-length thymosin beta-4, by contrast, is an endogenous peptide found broadly in mammalian cells and body fluids and is not identical to the synthetic TB-500 fragment (Review).
The biological rationale for thymosin beta-4 research comes from its role as an actin-binding peptide, meaning it interacts with actin, a protein that helps cells maintain shape and move during repair processes (Review). FDA materials describe TB-500 as containing the LKKTET sequence that makes up part of the actin-binding region thought to contribute to full-length thymosin beta-4 wound-healing properties, but FDA also distinguishes TB-500 from full-length thymosin beta-4 (FDA).
Manufacturing-origin information is important because TB-500 products discussed in compounding and research-use contexts are synthetic peptide substances rather than dietary ingredients or food-derived compounds (FDA). No ordinary food source of TB-500 was identified in the locked evidence set, and endogenous thymosin beta-4 research should not be interpreted as dietary exposure evidence (FDA).
How It Behaves in the Body
In plain terms, thymosin beta-4 research focuses on cell movement, tissue repair, inflammation control, and survival of stressed cells, because full-length thymosin beta-4 interacts with actin and has been studied in wound, corneal, and cardiovascular repair contexts (Review) (Review). Actin is part of the cell’s internal scaffolding, so substances that affect actin-related behavior may influence how cells migrate across an injured surface in experimental settings (Review).
TB-500 is often described as related to the actin-binding region of thymosin beta-4, but being related to a region of a larger peptide does not mean it has identical distribution, metabolism, potency, or clinical effects in humans (FDA). FDA noted that an in-vitro study using 50 μg/mL TB-500 did not promote scratch-wound closure in cultured fibroblasts, and FDA also reported that it did not identify published nonclinical in-vivo wound studies assessing TB-500 effects on wounds at the time of its evaluation (FDA).
Animal and in-vitro work suggests TB-500 can be metabolized into shorter peptides, and one rat/in-vitro study proposed that reported wound-healing activity may relate more to a metabolite than to parent TB-500 itself (Research). Equine work also detected TB-500 and metabolites in plasma and urine, supporting systemic exposure and metabolism in horses after administration (Research).
The better-established biology belongs to full-length thymosin beta-4 rather than TB-500, and reviews describe thymosin beta-4 as influencing cell migration, angiogenesis, inflammation, apoptosis, and extracellular-matrix remodeling in experimental and clinical-development contexts (Review) (Review). The less-established part is whether synthetic TB-500 reproduces those same effects in humans, because direct human administration data are lacking (FDA).
Absorption & Delivery Formats
Oral immediate-release: No verified human oral TB-500 pharmacokinetic or clinical study was identified in the locked evidence set, and FDA reported no published human PK studies of TB-500 by any route of administration (FDA). Oral peptide exposure would require separate study because peptides may have route-dependent stability and absorption properties, and no oral TB-500 evidence in humans was locked for this article (FDA).
Oral extended-release: No verified human extended-release oral TB-500 study was identified in the locked evidence set (FDA). Any claim about extended-release TB-500 absorption would therefore be speculative unless supported by future formulation-specific human PK research (FDA).
Sublingual: No verified human sublingual TB-500 absorption study was identified in the locked evidence set (FDA). Sublingual use discussed online should not be assumed to have predictable exposure without human PK data (FDA).
Transdermal: No verified human transdermal TB-500 absorption study was identified in the locked evidence set (FDA). Topical thymosin beta-4 gel studies in ulcers are not the same as transdermal systemic TB-500 delivery because they used full-length thymosin beta-4 in local wound contexts (Research).
Injectable / IV (research or clinical only): Human IV studies exist for full-length thymosin beta-4 and recombinant human thymosin beta-4, but FDA did not identify published human PK studies for administered TB-500 itself (Research) (Research) (FDA). Non-human TB-500 studies include horse subcutaneous administration and rat exposure contexts, which are useful for analytical and mechanistic interpretation but not for human dosing decisions (Research) (Research).
Quick Facts at a Glance
Onset (reported): No human onset timing has been established for TB-500 itself because FDA did not identify published human clinical or PK studies administering TB-500 (FDA). Ophthalmic thymosin beta-4 trials measured outcomes over days to weeks, but those studies used local full-length thymosin beta-4 formulations rather than TB-500 (Research).
Time to peak (Tmax): Human Tmax for TB-500 is not available from the locked evidence set (FDA). FDA summarized horse data in which subcutaneous TB-500 reached peak plasma concentrations between about 1 and 2 hours after treatment, but that is equine data and cannot be assumed to apply to humans (FDA).
Half-life (t½): Human half-life for TB-500 has not been established in the locked evidence set (FDA). Animal and in-vitro studies show metabolism into shorter fragments, but they do not define a validated human half-life (Research).
Typical duration: No typical human duration of TB-500 action can be stated from direct clinical evidence because direct human administration studies were not identified (FDA). Indirect thymosin beta-4 studies used durations such as 28 days in dry eye and up to several weeks or months in wound contexts, but those durations belong to specific formulations and trial designs (Research) (ClinicalTrials.gov).
Absorption routes studied: For TB-500 itself, the locked evidence includes non-human systemic detection after subcutaneous horse administration and rat/in-vitro metabolism studies (Research) (Research). For full-length thymosin beta-4, human studies include topical, ophthalmic, and IV formulations (Research) (Research).
Formulation differences: Formulation differences are central because TB-500, full-length synthetic thymosin beta-4, recombinant human thymosin beta-4, ophthalmic RGN-259, and topical gel preparations are not interchangeable evidence categories (FDA). FDA specifically cautioned that TB-500 and full-length thymosin beta-4 are not the same substance, so article claims must maintain that distinction (FDA).
Variability drivers: Likely variability drivers include molecular identity, salt/free-base form, peptide purity, route of administration, local versus systemic delivery, and whether the study used TB-500 or full-length thymosin beta-4 (FDA). FDA also identified peptide-related impurities and aggregation as safety-relevant concerns for compounded drugs containing thymosin beta-4 fragment LKKTETQ (FDA).
Tolerance / adaptation: No verified human tolerance or adaptation study for TB-500 was identified in the locked evidence set (FDA). Recombinant human thymosin beta-4 phase I research monitored anti-drug antibodies, but those data apply to a full-length recombinant molecule rather than TB-500 (Research).
Evidence strength snapshot: Direct TB-500 evidence is emerging and incomplete, with no identified administered-human clinical evidence in FDA’s review (FDA). Indirect full-length thymosin beta-4 evidence is stronger in Eye Health and Beauty and Skin Health than in Muscle Health or Joint Health, where claims remain mainly non-human or community-driven (Research) (Reuters).
Other Physiological Contexts Studied (If Applicable)
- Direct TB-500 in-vitro and rat metabolism: A 2024 study quantified TB-500 and metabolites in in-vitro experiments and rats, and the authors reported that wound-healing activity may relate to the Ac-LKKTE metabolite rather than parent TB-500 (Research).
- Equine detection and metabolism: A doping-control study detected N-acetylated LKKTETQ and metabolites in equine urine and plasma after TB-500 administration, supporting systemic detection in horses but not human efficacy (Research).
- Dermal wound-healing models: Full-length thymosin beta-4 accelerated wound repair in rat full-thickness wound models and in diabetic and aged mouse wound models, but those are non-human thymosin beta-4 studies rather than direct human TB-500 studies (Research) (Research).
- Corneal injury models: Mouse corneal alkali-injury research reported faster re-epithelialization and reduced inflammatory-cell infiltration after topical thymosin beta-4, supporting ocular research rationale but not direct TB-500 clinical claims (Research).
- Ligament and tendon models: Rat medial collateral ligament research reported histological and mechanical healing signals with thymosin beta-4, and a 2026 rat Achilles tendon study evaluated BPC-157, TB-500, and their combination (Research) (Research).
- Neurological injury models: Rat traumatic brain injury research has examined thymosin beta-4 in neurorepair-related outcomes, but this does not establish a human neurological use for TB-500 (Research).
- Cardiac animal models: Thymosin beta-4 cardiac studies include mouse and pig models with mixed findings, including a pig ischemia-reperfusion study that did not demonstrate cardioprotection in that model (Research) (Research).
Safety, Interactions & Regulation
Human safety data for TB-500 itself are not established in the locked evidence set, and FDA reported no identified human exposure data for drug products containing thymosin beta-4 fragment LKKTETQ (FDA). FDA also stated that compounded drugs containing the fragment may pose immunogenicity risk for certain routes of administration due to potential aggregation and peptide-related impurities (FDA).
Full-length thymosin beta-4 phase I studies reported controlled safety and PK observations in healthy volunteers, but those findings should not be transferred directly to TB-500 because the molecules are different (Research) (Research). Ophthalmic thymosin beta-4 trials also reported ocular safety observations in specific clinical settings, but those data apply to local eye-drop formulations rather than systemic TB-500 use (Research).
Interaction evidence for TB-500 is poorly characterized because no direct human interaction studies were identified in the locked evidence set (FDA). Theoretical interaction concerns should be framed cautiously because peptide identity, impurities, immune response, route of administration, and concurrent experimental peptide use may all affect risk, but those factors have not been systematically studied for TB-500 in humans (FDA).
Population cautions are broad because pregnant people, lactating people, children, older adults with comorbidities, immunocompromised people, competitive athletes, and people using multiple injectable peptides were not represented in direct TB-500 human trials in the locked evidence set (FDA). This lack of population-specific evidence is especially important for injectable or multi-peptide use because FDA has highlighted immunogenicity and impurity concerns for compounded peptide fragments (FDA).
In the United States, FDA lists “Thymosin beta-4, fragment (LKKTETQ), also known as TB-500” among bulk drug substances that may present significant safety risks in compounding (FDA). FDA’s July 2026 PCAC materials addressed TB-500 free base and TB-500 acetate as bulk drug substances nominated for 503A compounding review, and those materials reported no identified published human clinical studies administering TB-500 (FDA) (FDA).
In the European clinical-trial context, an EU Clinical Trials Register record documents a thymosin beta-4 gel study for venous stasis ulcers, but that record supports trial activity for thymosin beta-4 gel rather than EU authorization of TB-500 for general use (EU CTR). No broad EMA approval claim for TB-500 is supported by the locked evidence set, so EU regulatory wording should remain limited to documented trial-registry context (EU CTR).
In sport, WADA prohibited-list materials have listed thymosin beta-4 and its derivatives, including TB-500, in the peptide-hormone and growth-factor context (WADA). Competitive athletes should treat anti-doping status as a separate regulatory issue from clinical evidence, because a prohibited-list designation does not prove safety or efficacy (WADA).
Evidence Overview
The overall evidence landscape for TB-500 is best described as indirect, molecule-adjacent, and early, because direct administered-human TB-500 studies were not identified by FDA, while several human studies exist for full-length thymosin beta-4 formulations (FDA) (Research). The strongest adjacent human evidence is in Eye Health, where ophthalmic thymosin beta-4 trials have studied neurotrophic keratopathy and dry eye, and in Beauty and Skin Health, where topical thymosin beta-4 gel has been studied in venous and pressure-ulcer contexts (Research) (Research). Confidence is not higher because TB-500 is a shorter synthetic fragment, and FDA explicitly distinguishes it from full-length thymosin beta-4 (FDA).
The human thymosin beta-4 literature includes randomized ophthalmic trials, topical wound studies, phase I IV safety/PK studies, and trial registrations, but these study types answer different questions and use different formulations (Research) (ClinicalTrials.gov). Ophthalmic studies are local-delivery studies and cannot be used to infer systemic TB-500 effects after injection or oral use (Research). IV phase I studies help characterize full-length thymosin beta-4 exposure and tolerability but do not establish TB-500 efficacy or fragment-specific pharmacokinetics (Research).
Non-human TB-500 and thymosin beta-4 studies provide useful mechanistic context, especially for cell migration, wound models, corneal injury, tendon or ligament repair, and peptide metabolism (Research) (Research). However, FDA’s evaluation noted the absence of published clinical TB-500 administration data and the absence of identified nonclinical toxicity studies sufficient to inform clinical safety considerations for potential TB-500 uses (FDA). That gap matters because peptide fragments can differ in metabolism, receptor or binding behavior, impurity profile, aggregation risk, and immune response from full-length proteins or peptides (FDA).
Community attention is real but should be interpreted separately from evidence quality. Reuters reported that BPC-157 and TB-500 have become increasingly popular and that their combination is popularly known as the “Wolverine stack,” but popularity and anecdotal use do not establish controlled human efficacy or safety (Reuters). A rat Achilles tendon study evaluating BPC-157, TB-500, and their combination is relevant to why the pairing is discussed, but it remains animal evidence and cannot validate a human stacking protocol (Research).
Future confidence would require verified molecule-specific TB-500 studies, including identity-controlled formulations, human pharmacokinetics, dose-ranging, adverse-event monitoring, immunogenicity assessment, and randomized controlled trials in clearly defined populations (FDA). Until such studies exist, the most accurate evidence classification keeps TB-500 separate from full-length thymosin beta-4 and treats peptide-community use as informal context rather than clinical evidence (FDA).
Evidence Confidence Classification
Emerging / Limited is the overall human evidence classification for TB-500 because FDA did not identify published human clinical or human pharmacokinetic studies administering TB-500 itself, while adjacent human evidence comes from full-length thymosin beta-4 formulations (FDA). The strongest molecule-adjacent evidence appears in Eye Health and Beauty and Skin Health, but those studies used ophthalmic or topical thymosin beta-4 rather than TB-500 (Research) (Research). The evidence is not Moderate or Strong for TB-500 itself because direct human dosing, efficacy, safety, interaction, and PK data are missing in the locked evidence set (FDA).
Similar Ingredients & Comparators
Similar supplement-style or peptide-community ingredients:
- BPC-157
- Full-length thymosin beta-4
- Thymosin alpha-1
- KPV
- GHK-Cu
- MOTS-c
- Epitalon
- Semax
- CJC-1295
- Ipamorelin
- Ac-SDKP
Medical / pharma comparator categories:
- FDA-approved wound-care therapies
- Prescription ophthalmic therapies for dry eye
- Approved biologic therapies for neurotrophic keratopathy
- Standard cardiovascular reperfusion and post-MI therapies
- Physical rehabilitation and orthopedic care approaches
- Regulated injectable peptide and protein medicines
Combination Context
TB-500 + BPC-157:
TB-500 plus BPC-157 is commonly discussed online as the “Wolverine stack,” and Reuters reported that the pairing has become popularly known by that name in peptide-community and wellness-market contexts (Reuters). A 2026 rat Achilles tendon study evaluated BPC-157, synthetic thymosin beta-4/TB-500, and their combination, but this remains animal evidence rather than a validated human protocol (Research).
Thymosin beta-4 + vasoactive intestinal peptide (VIP):
A human corneal epithelial cell study examined thymosin beta-4 with vasoactive intestinal peptide under high-glucose conditions to explore barrier integrity, wound-healing behavior, and inflammation-related signaling in vitro (Research). This is a cell-study combination context and should not be interpreted as a human clinical combination regimen (Research).
Thymosin beta-4 + Ac-SDKP:
Reviews discuss thymosin beta-4 and its tetrapeptide derivative Ac-SDKP in cardiac-healing research, especially in relation to inflammation, fibrosis, and tissue repair after infarction (Review). This combination or derivative context is mechanistic and translational rather than evidence that TB-500 plus Ac-SDKP has proven clinical effects (Review).
FAQ
What is TB-500?
TB-500 is a synthetic N-acetylated peptide fragment corresponding to residues 17–23 of thymosin beta-4, commonly represented as Ac-LKKTETQ (Research). It is not the same molecule as full-length thymosin beta-4, which is a 43–amino-acid endogenous peptide (FDA). This distinction matters because most human research has studied full-length thymosin beta-4 formulations rather than TB-500 itself (FDA).
What does human research study it for?
Direct human research on administered TB-500 was not identified by FDA in its reviewed materials (FDA). Human research adjacent to TB-500 has studied full-length thymosin beta-4 in Eye Health, Beauty and Skin Health, and Cardiovascular Health contexts (Research) (Research). Those studies include ophthalmic, topical, and IV formulations that should not be treated as interchangeable with TB-500 (FDA).
What are the best-supported uses?
The best-supported adjacent human research areas are Eye Health and Beauty and Skin Health because these areas include randomized ophthalmic trials and topical wound studies with full-length thymosin beta-4 formulations (Research) (Research). This does not mean TB-500 has proven human benefits in those areas, because TB-500 itself has not been established as clinically equivalent to full-length thymosin beta-4 (FDA). The most accurate wording is that thymosin beta-4 research provides indirect context for TB-500 discussions (FDA).
Where is evidence mixed or limited?
Evidence is most limited for TB-500 itself because direct administered-human studies and human PK studies were not identified by FDA (FDA). Evidence is also limited for Muscle Health and Joint Health because the most relevant direct TB-500 material includes animal, in-vitro, and community-use contexts rather than controlled human trials (Research) (Reuters). Full-length thymosin beta-4 findings cannot be automatically transferred to TB-500 because the molecules differ (FDA).
How quickly does it act?
No verified human onset time has been established for TB-500 itself because direct human clinical and PK data were not identified in FDA’s review (FDA). In horses, FDA summarized TB-500 plasma peaks about 1–2 hours after subcutaneous treatment, but that finding is non-human and cannot define human onset (FDA). Ophthalmic thymosin beta-4 trials measured clinical changes over trial periods such as 28 days, but those studies used local eye-drop formulations rather than TB-500 (Research).
What affects absorption and variability?
Absorption and variability likely depend on molecule identity, formulation, route of administration, local versus systemic delivery, and peptide quality, but direct human TB-500 PK evidence is absent in the locked evidence set (FDA). FDA identified concerns about aggregation and peptide-related impurities for compounded drugs containing thymosin beta-4 fragment LKKTETQ (FDA). Full-length thymosin beta-4 topical, ophthalmic, and IV studies should be interpreted as formulation-specific evidence rather than general TB-500 absorption evidence (Research).
Is tolerance reported?
No verified human tolerance or adaptation study for administered TB-500 was identified in the locked evidence set (FDA). Recombinant human thymosin beta-4 phase I research monitored anti-drug antibodies, but that study used full-length recombinant thymosin beta-4 rather than TB-500 (Research). This means tolerance claims for TB-500 should remain unconfirmed unless future human studies directly measure them (FDA).
Why do studies disagree?
Apparent disagreements often arise because sources discuss different molecules: TB-500, full-length thymosin beta-4, recombinant thymosin beta-4, RGN-259 ophthalmic solution, or topical thymosin beta-4 gel (FDA). Results also differ because studies use different routes, populations, endpoints, and species, including human ocular trials, human wound studies, horse PK work, rat models, and in-vitro experiments (Research) (Research). The most important interpretive rule is that full-length thymosin beta-4 evidence should not be relabeled as direct TB-500 evidence (FDA).
What ingredients is it commonly combined with and why?
TB-500 is commonly discussed with BPC-157 in peptide communities under the informal name “Wolverine stack” (Reuters). The rationale usually described online is tissue repair or injury recovery, but that rationale is not the same as controlled human evidence (Reuters). A rat Achilles tendon study evaluated BPC-157, TB-500, and their combination, but it remains non-human evidence and does not validate a human stack protocol (Research).
What foods naturally contain this ingredient?
No ordinary food source of TB-500 was identified in the locked evidence set because TB-500 is a synthetic peptide fragment rather than a documented dietary nutrient (Research). Full-length thymosin beta-4 is endogenous in mammalian tissues and body fluids, but endogenous biological occurrence is not the same as dietary intake evidence (Review). Therefore, TB-500 should not be described as a naturally occurring food ingredient based on the locked evidence set (FDA).
How is it regulated?
In the United States, FDA lists thymosin beta-4 fragment LKKTETQ, also known as TB-500, among bulk drug substances that may present significant safety risks in compounding (FDA). FDA’s July 2026 PCAC materials reviewed TB-500 free base and TB-500 acetate in the 503A bulk-drug-substance context (FDA). In sport, WADA materials list thymosin beta-4 derivatives including TB-500 as prohibited substances (WADA).
Resources
- FDA TB-500 PCAC presentation — U.S. FDA — https://www.fda.gov/media/193773/download
- FDA TB-500 briefing document — U.S. FDA — https://www.fda.gov/media/193349/download
- FDA compounding safety-risk list — U.S. FDA — https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks
- TB-500 analytical identity study — PubMed — https://pubmed.ncbi.nlm.nih.gov/22962027/
- TB-500 rat/in-vitro metabolism study — PubMed — https://pubmed.ncbi.nlm.nih.gov/38382158/
- TB-500 equine detection study — PubMed — https://pubmed.ncbi.nlm.nih.gov/23084823/
- IV thymosin beta-4 phase I study — PubMed — https://pubmed.ncbi.nlm.nih.gov/20536472/
- Recombinant human thymosin beta-4 phase I study — PubMed — https://pubmed.ncbi.nlm.nih.gov/34346165/
- RGN-259 neurotrophic keratopathy trial — PubMed — https://pubmed.ncbi.nlm.nih.gov/36613994/
- RGN-259 dry eye phase 2 trial — PubMed — https://pubmed.ncbi.nlm.nih.gov/26056426/
- Venous-ulcer thymosin beta-4 study — PubMed — https://pubmed.ncbi.nlm.nih.gov/20536470/
- Reuters report on FDA peptide review and “Wolverine stack” — Reuters — https://www.reuters.com/legal/litigation/us-fda-advisers-weigh-restrictions-seven-peptides-industry-presses-expansion-2026-07-23/