Thymosin Beta-4
clinical trialsAlso known as: Tβ4, Timbetasin
**Mechanism of Action** Thymosin Beta-4 (Tβ4) is a 43-amino acid actin-sequestering peptide that binds monomeric G-actin, preventing its polymerization into F-actin filaments. This dynamic regulation of the cytoskeleton promotes cell migration, proliferation, and differentiation. Tβ4 also upregulates matrix metalloproteinases (e.g., MMP-2, MMP-9), stimulates angiogenesis via vascular endothelial growth factor (VEGF) signaling, and reduces inflammation by inhibiting nuclear factor kappa B (NF-κB) activation. These actions collectively support tissue repair in cardiac, corneal, and dermal tissues. **Key Research Findings** In preclinical models, Tβ4 enhances cardiac repair post-myocardial infarction by reducing scar size, improving left ventricular function, and promoting cardiomyocyte survival. Corneal studies show accelerated epithelial wound healing and reduced fibrosis after injury. Dermal applications demonstrate increased collagen deposition, angiogenesis, and faster wound closure in diabetic and burn wounds. Clinical trials (e.g., NCT01311518, NCT01435395) have evaluated Tβ4 for acute myocardial infarction, corneal ulcers, and pressure ulcers, with phase II data indicating improved healing rates and reduced inflammation. However, larger phase III trials are needed to confirm efficacy and safety. **Clinical Relevance** Tβ4 is under investigation as a therapeutic for ischemic heart disease, corneal injuries, and chronic wounds. Its pleiotropic effects—modulating actin dynamics, inflammation, and angiogenesis—position it as a potential regenerative agent. Current clinical use remains investigational, with no FDA-approved indications. Adverse effects in trials have been mild (e.g., injection site reactions), but long-term safety data are limited. For research purposes only — not medical advice.
Key data
C212H350N56O78SResearch & studies
In mice, 7-day rhTB4 treatment prevented cardiac dysfunction and fibrosis 28 days post-I/R and reduced plasma NT-proBNP levels.; rhTB4 activated the ErbB2/Raf1 signaling pathway, attenuated cardiomyocyte apoptosis, and suppressed Bad expression in vitro; ErbB2 inhibition abolished its cardioprotective effects.; In STEMI patients, rhTB4 given within 8 hours post-PCI significantly reduced infarcted areas at 90-day follow-up compared to placebo, but overall differences across all 96 patients were not significant.
fAD organoids showed decreased mature neurons and increased cell senescence and Aβ production.; TMSB4X gene expression was reduced in fAD organoid neurons and AD patient excitatory neurons.; Tβ4 treatment rescued neurodevelopmental deficits and Aβ formation in fAD organoids.; Beneficial effects of Tβ4 were also observed in 5xfAD model mice.
TB4 significantly increases miR139-5p expression and targets ROCK1 protein in adult mouse hearts and human cardiac cells.; TB4 modulates ROCK1 levels both in vivo and in vitro, as confirmed by real-time PCR, Western blot, and immunostaining.; TB4 may reverse or inhibit fibroblast/myofibroblast transformation through cell-type-specific downstream mechanisms involving ROCK1.; The study proposes TB4 as a potential ROCK1 inhibitor for future therapeutic use in cardiac remodeling.
Combined MSC and Tβ4 therapy outperformed monotherapies in dry eye recovery.; Glutamine levels increased in cornea after combined therapy; inhibiting glutamine reversed therapeutic effects.; Glutaminase (GLS1) expression was elevated after dry eye injury; GLS1 inhibition enhanced anti-inflammatory effects.; Glutamine treatment reduced pro-inflammatory and pro-fibrotic corneal epithelial cell subclusters and related IκB/NF-κB signaling.
Expression of thymosin β4 and β10 was studied from fetal development to different postnatal ages in human organs.; Proteomics on preterm newborn saliva and gingival crevicular fluid revealed the importance of these acidic peptides.; Immunochemistry showed distribution of thymosin β4 and β10 in adult and fetal organs, suggesting functions in health and disease.; Functions during carcinogenesis add details to resolve the 'β-thymosin enigma' regarding their molecular roles in development.
Thymosin beta 4 is a naturally occurring protein that promotes corneal wound healing and reduces inflammation.; Current treatments for bacterial keratitis, such as antibiotics and corticosteroids, do not fully address visual outcomes or have harmful side effects.; In experimental models, adjunctive thymosin beta 4 with ciprofloxacin reduced inflammatory mediators and infiltrates while enhancing bacterial killing and wound healing.; Thymosin beta 4 is in Phase 3 clinical trials for dry eye disease, suggesting potential for clinical development in keratitis.
TB4 is expressed in the developing mouse heart and promotes cardiac cell migration and survival.; In adult mice, TB4 injection after coronary artery ligation enhances myocyte survival and improves cardiac function.; TB4 alters adult epicardial morphology to resemble embryonic characteristics and increases cardiac vessel number.; TB4 activates epicardial progenitors independently of hypoxic injury.
Tβ4 increased the expression of tight junction protein in hCMEC/D3 cells.; Tβ4 reduced the ratio of F-actin to G-actin in hCMEC/D3 cells.; Tβ4 significantly improved PrP(106-126)-induced vascular permeability dysfunction.; PrP(106-126) disrupted tight junctions and cytoskeleton arrangement in an in vitro BBB model.
Frequently asked questions
What is Thymosin Beta-4?
**Mechanism of Action** Thymosin Beta-4 (Tβ4) is a 43-amino acid actin-sequestering peptide that binds monomeric G-actin, preventing its polymerization into F-actin filaments. This dynamic regulation of the cytoskeleton promotes cell migration, proliferation, and differentiation. Tβ4 also upregulates matrix metalloprot
How does Thymosin Beta-4 work?
43-aa actin-sequestering peptide that drives cell migration, angiogenesis, and repair in cardiac, corneal, and dermal tissue.
What is the research status of Thymosin Beta-4?
Thymosin Beta-4 is currently classified as clinical trials, with 602 research references on record. This is for research purposes only and is not medical advice.
What is the molecular weight of Thymosin Beta-4?
Thymosin Beta-4 has a molecular weight of approximately 4963 g/mol (formula C212H350N56O78S).
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