TB-500
Animal-onlyThymosin Beta-4 · Thymosin β4 · Tβ4 · TB500 · Thymosin beta 4 fragment
Limited evidence: the strongest curated study is Animal-only; no human-trial data found as of 2026-06-04.
Chemical & identity
- Sequence
- LKKTETQ
- Length
- 7 residues
- Molecular formula
- C38H68N10O14
- Molecular weight
- 889 g/mol · PubChem
- PubChem CID
- 62707662 · PubChem
- SMILES
- C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)C)O
- InChIKey
- ADKDNDYYIZUVCZ-ZQNQAVPYSA-N
- UniProt
- P62328 · UniProt
- Category
- Healing/Recovery
Chemical/structural fields are auto-pulled and source-linked.
Mechanism (curated)
No established mechanism of action has been curated yet.
Research
McGuire F et al. · 2026 · Systematic review
This scoping review mapped the evidence on thymosin beta-4 (TB4) and TB-500 in tissue healing and musculoskeletal repair by searching PubMed, Europe PMC, and ClinicalTrials.gov through March 2026, identifying 80 studies from 1772 records. The evidence base was weighted toward mixed and in vitro designs, with most studies evaluating TB4 rather than TB-500. Human evidence was concentrated in ocular/cornea and wound/skin/soft tissue settings, while direct musculoskeletal applications (tendon, ligament, muscle, cartilage, spine) were sparse. The authors conclude that the literature supports interest in repair-related pathways but remains largely preclinical with limited human evidence directly relevant to musculoskeletal use, and direct TB-500 evidence was limited to a single included study.
Ding Y et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025 · Other
This study describes engineered adipose-derived stem cell extracellular vesicles (ADSC-EVs) modified with Thymosin β4 (Tβ4) and delivered via separable microneedle patches (MN@EVs^Tβ4) for diabetic wound healing. The patches were designed using gelatin methacryloyl and poly(ethylene glycol) diacrylate to encapsulate and sustain release of EVs^Tβ4, with a hyaluronic acid base layer that dissolves upon exudate absorption. The study demonstrated that EVs^Tβ4 mitigate cellular senescence and improve function via the PTEN/PI3K/AKT pathway. In diabetic wound models, MN@EVs^Tβ4 patches showed significant efficacy in reversing senescence and promoting wound healing.
Ying Y et al. · International journal of molecular sciences · 2024 · Other
This study investigates how thymosin β4 (Tβ4), a G-actin sequestering peptide, affects thymocyte differentiation through regulation of cytoskeletal rearrangement and mitochondrial transfer in thymic epithelial cells (TECs). Using techniques including H&E staining, immunofluorescence, transmission electron microscopy, RT-qPCR, flow cytometry, and immunolabeling, the researchers examined Tβ4's effects on TEC skeleton rearrangement, mitochondrial transfer, and thymocyte differentiation. The study found that Tβ4 primarily regulates microfilament formation and mitochondrial transfer in TECs, along with formation and maturation of double-negative cells and CD4 single-positive thymocytes. The authors conclude that Tβ4 plays a crucial role in thymocyte differentiation, possibly through its impact on F-actin aggregation. The study suggests these findings may have implications for research in immune aging.
Ebrahim AS et al. · Biosensors · 2023 · In-vitro study
A study investigated combination therapy with thymosin beta-4 (Tβ4) and vasoactive intestinal peptide (VIP) in human corneal epithelial cells exposed to high glucose (25 mM) versus normal glucose (5 mM). Using electric cell-substrate impedance sensing, the researchers measured barrier function, wound healing, and tight junction protein expression. High glucose significantly impaired barrier integrity and wound healing, but Tβ4/VIP treatment (0.1% Tβ4 and 5 nM VIP) improved both measures and maintained tight junction proteins (ZO-1, ZO-2, occludin, claudin-1) at levels similar to normal glucose conditions. The authors conclude that Tβ4 and VIP work synergistically to protect corneal epithelial cells against hyperglycemia-induced damage.
Stewart WG et al. · Scientific reports · 2025 · In-vitro study
This in-vitro study investigated thymosin β4 (Tβ4) effects on hypoxia-induced blood-brain barrier (BBB) dysfunction in human brain microvascular endothelial cells (hBMVECs). Pretreatment with Tβ4 reversed hypoxia-induced damage to tight junction proteins and reduced endothelial cell permeability. The protective mechanism appeared to depend on sphingosine 1-phosphate receptor 1 (S1PR1), as inhibiting S1PR1 blocked Tβ4's protective effects. The authors propose that Tβ4 may be a promising therapeutic target for BBB integrity in conditions like traumatic brain injury and cerebral ischemia, warranting further investigation.
Wang M et al. · Journal of neuroinflammation · 2021 · Animal study
This study investigated thymosin β4 (Tβ4) effects on Alzheimer's disease pathology in APP/PS1 transgenic mice. Tβ4 overexpression reduced brain amyloid-β accumulation, reversed glial cell polarization, improved neuronal function, and enhanced cognitive performance and mood-related behaviors. The mechanism involved downregulation of both classical and non-canonical NF-κB signaling pathways (TLR4/MyD88/NF-κB p65 and p52), as blocking these pathways separately did not provide additional benefits. The authors conclude that Tβ4 may serve as a potential therapeutic target for Alzheimer's disease through NF-κB pathway regulation.
Hao M et al. · Experimental cell research · 2024 · Animal study
This study examined thymosin β4 (Tβ4) expression and function in inflammatory bowel disease using a mouse model of DSS-induced colitis and cultured human colon cells. The researchers found that Tβ4 expression was upregulated in colitis mice and that intraperitoneal injection of Tβ4 in mice impaired intestinal mucus barrier function, decreased mucin2 levels, disrupted tight junctions, and inhibited autophagy (as measured by LC3II protein). These effects were confirmed in cultured human colon carcinoma cells and normal human colon tissue. The study concludes that Tβ4 may compromise intestinal barrier integrity by inhibiting autophagy and suggests it could serve as a diagnostic marker for intestinal barrier defects.
Zhu Z et al. · Journal of inflammation research · 2025 · Animal study
This animal study examined thymosin β4 (Tβ4) in a mouse model of nonalcoholic fatty liver disease (NAFLD) induced by methionine and choline-deficient diet. Researchers used siRNA to reduce liver Tβ4, observed macrophage responses with clodronate liposomes, and performed histological and in vitro experiments with human hepatic and myeloid cells. Results showed that Tβ4 treatment reduced liver inflammation and steatosis, promoted M2-type macrophage polarization, decreased M1 phenotype expression, and modulated STAT1 phosphorylation and SOCS1/3 expression. The authors propose Tβ4 as a potential therapeutic approach for NAFLD based on its effects on macrophage polarization.
Lachowicz JI et al. · International journal of molecular sciences · 2026 · In-vitro study
This study investigates zinc coordination by thymosin β4 (Tβ4), a 43-amino-acid acidic peptide, using multiple biophysical techniques including mass spectrometry, NMR spectroscopy, and electron microscopy. The researchers demonstrate that Tβ4 forms discrete Zn(II)-bound complexes with a 1:3 peptide-to-zinc molar ratio and undergoes zinc-induced aggregation under physiological pH conditions. Aggregation occurs through charge neutralization of Tβ4's negative surface charge but is predicted to be unlikely in plasma or basal interstitial environments; however, it may occur in zinc-rich microdomains such as the synaptic cleft where zinc levels exceed 1 μM. The findings suggest that Zn(II)-mediated supramolecular assembly of Tβ4 could influence peptide behavior in neurological or inflammatory conditions with elevated extracellular zinc.
Liang Y et al. · Nature communications · 2026 · Animal study
This study describes a hydrogel combining decidualized endometrial extracellular matrix (DEndo-UdECM) with sustained release of thymosin β4 (Tβ4) for treating intrauterine adhesions (IUA) in a murine model. A single administration of the hydrogel restored endometrial architecture, resolved fibrosis, and led to near-complete recovery of fertility in the IUA model. Mechanistically, the hydrogel promoted an anti-fibrotic response by reprogramming macrophages to an M2 phenotype, inhibiting pyroptosis-driven inflammation, and inhibiting the TGF-β/Smad3 fibrotic pathway. The study was conducted in mice; human efficacy and safety have not been evaluated in this abstract.
Zhang GH et al. · PloS one · 2023 · In-vitro study
This in-vitro study examined thymosin β4 (Tβ4) effects in an Alzheimer's disease cell model using SH-SY5Y neuroblastoma cells treated with β-amyloid. Tβ4 overexpression increased cell viability, decreased apoptosis (reducing Caspase-3, Caspase-8, and Bax while upregulating Bcl-2), and reduced oxidative stress markers (MDA, LDH, ROS) while increasing antioxidant markers (SOD, GSH-PX). The protective effects were associated with inhibition of ERK/p38 MAPK signaling and increased 5-HTR1A expression. The authors conclude that Tβ4 demonstrates neuroprotective potential in an Alzheimer's disease model, suggesting possible therapeutic applications.
Li Y et al. · The Journal of allergy and clinical immunology · 2025 · Animal study
This study investigated the role of plasmacytoid dendritic cells (pDCs) in allergic asthma using mouse models with pDC depletion and house mite dust challenge. RNA sequencing of lung pDCs identified thymosin β4 (Tβ4) as a highly upregulated anti-inflammatory peptide in asthmatic lungs, induced by airway epithelial cell-derived IL-33. Tβ4 supplementation reversed asthma exacerbation in pDC-depleted mice by inhibiting JAK1/STAT6 signaling in alveolar macrophages, reducing CCL2 expression and inflammatory monocyte recruitment. The study found that serum Tβ4 levels were decreased in both mice and humans with ongoing allergic asthma, suggesting potential therapeutic value of Tβ4 for allergic asthma.
Sun YS et al. · World journal of gastroenterology · 2025 · Animal study
This study investigates thymosin β4 (Tβ4) released by mast cells under stress conditions in irritable bowel syndrome (IBS). Using animal models (Tβ4-deficient rats and mast cell-deficient mice) and in vitro assays, researchers found that elevated Tβ4 levels impair intestinal epithelial barrier function by suppressing the IL22RA1/JAK1/STAT3 signaling pathway. Tβ4 release from mast cells was triggered by corticotropin-releasing hormone (CRH) receptor 1 signaling rather than degranulation, and Tβ4-deficient rats showed resistance to stress-induced barrier dysfunction. The authors conclude that Tβ4 plays a central role in IBS pathogenesis through this mechanism and may be a therapeutic target.
Summaries are our own; we link to originals (PubMed / DOI) and never rehost full text.
Regulatory status
- FDA approved
- No
- WADA prohibited
- Yes
- Compounding status
- No FDA-approved therapeutic formulation; sold as a research chemical.
- Notes
- Not FDA-approved — no approved therapeutic formulation as of 2026-06-04. Prohibited in sport under WADA (peptide/growth-factor class).
Legal/regulatory status varies by jurisdiction and changes over time — accurate as of last review (2026-06-04).
Data sources: Curated IDs (PubChem/UniProt/ChEMBL) + Europe PMC + ClinicalTrials.gov (2026-06-04).
Last reviewed 2026-06-04