Description
- TB-500 (Thymosin Beta-4 Fragment)
For Research & Laboratory Use Only
Overview
TB-500 is a synthetic peptide modeled after the naturally occurring protein Thymosin beta-4 (Tβ4). Native Tβ4 is widely expressed in mammalian tissues and is encoded by the TMSB4X gene, with high concentrations observed in the thymus and in wound environments. Experimental research suggests that TB-500 may mirror many of Tβ4’s potential biological activities, including support of angiogenesis, modulation of wound repair, and possible influence on cell migration, tissue remodeling, and hair follicle dynamics.(1)
TB-500 is a 43–amino acid peptide, highly water-soluble and relatively low in molecular weight compared to larger proteins. It has been detected in high levels within wound fluid and platelet-rich environments. Preclinical data propose that TB-500/Tβ4 may exhibit anti-inflammatory, cytoprotective, and pro-reparative properties, with possible roles in neurological, cardiac, spinal, and cutaneous tissue models.(1)
Mechanistic Background
Actin Dynamics and Cell Motility
TB-500 (Thymosin β4) contains a characteristic peptide motif, (17)LKKTETQ(23), which is considered a key functional sequence for actin binding and regulation.(2)
The full amino acid sequence of TB-500 is:
Ac-Ser-Asp-Lys-Pro-Asp-Met-Ala-Glu-Ile-Glu-Lys-Phe-Asp-Lys-Ser-Lys-Leu-Lys-Lys-Thr-Glu-Thr-Gln-Glu-Lys-Asn-Pro-Leu-Pro-Ser-Lys-Glu-Thr-Ile-Glu-Gln-Glu-Lys-Gln-Ala-Gly-Glu-Ser-OH
Actin proteins form a core component of the cellular cytoskeleton and are essential for maintaining cell structure, motility, and shape. TB-500/Tβ4 is believed to interact primarily with globular actin (G-actin), sequestering it and preventing its polymerization into filamentous actin (F-actin). This “actin-sequestering” effect increases the pool of available G-actin, thereby influencing cytoskeletal remodeling and potentially impacting cell movement and morphology.(3)
Because cellular migration underlies processes such as wound closure, tissue regeneration, neovascularization, and even metastatic behavior in tumor models, the actin-regulating properties of TB-500 remain a key focus of ongoing research.
Intracellular and Extracellular Roles
Thymosin beta-4 has been identified both within cells and in extracellular compartments, including blood plasma and wound exudates.(11,12) Experimental data in vascular and endothelial cells suggest that extracellular Tβ4 may:
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Enhance cellular motility
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Support new blood vessel formation (angiogenesis)
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Interact with cell-surface ATP synthase, influencing local energy-related signaling
These findings indicate that TB-500/Tβ4 may operate across multiple compartments, affecting cytoskeletal dynamics, cell migration, and vascular responses at both intra- and extracellular levels.
Chemical Makeup
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Molecular Formula: C₂₁₂H₃₅₀N₅₆O₇₈S
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Molecular Weight: 4963 g/mol
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Other Names: Thymosin Beta-4 (synthetic fragment), Tβ4 Analog
Research and Experimental Studies
1. TB-500 and Inflammation
Preclinical work suggests that Tβ4/TB-500 may modulate inflammatory signaling via microRNA-146a (miR-146a).(4) In one study, Tβ4 upregulated miR-146a, which is thought to negatively regulate components of Toll-like receptor signaling, including:
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IRAK1 (IL-1 receptor-associated kinase 1)
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TRAF6 (TNF receptor-associated factor 6)
When anti–miR-146a nucleotides were introduced, the inhibitory effect of Tβ4 on IRAK1 and TRAF6 was reportedly reversed, supporting miR-146a as a downstream mediator. These data suggest that TB-500/Tβ4 may contribute to anti-inflammatory potential through suppression of proinflammatory signaling pathways.
2. TB-500 and Acute Wound Models
A 1999 murine wound study evaluated synthetic Thymosin beta-4 (TB-500) in full-thickness skin injuries.(5)
Reported findings included:
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~41% greater re-epithelialization after 4 days compared to saline controls
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~11% more wound contraction after 7 days relative to controls
Histologic and morphometric analysis led researchers to propose that TB-500 may enhance angiogenesis and collagen deposition, ultimately accelerating wound closure. The authors described Tβ4 as a “potent wound-healing factor” with multiple biological activities.
3. TB-500 and Chronic Wounds
Additional animal studies examined TB-500 across several challenging wound environments, including:
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Normal mice and rats
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Diabetic mice
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Aged mice
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Steroid-treated rats
In each setting, TB-500 appeared to speed wound closure compared with controls.(6) Phase 2 clinical investigations in models of stasis and pressure ulcers further suggested that Tβ4/TB-500 application might shorten healing time by up to one month in certain contexts. These results point toward a potential supportive role in impaired or chronic wound models, though this remains in the experimental domain.
4. TB-500 and Cardiac Tissue
Pulmonary hypertension is characterized by increased resistance in the pulmonary vasculature, which can result in right ventricular hypertrophy and eventual heart failure. In monocrotaline (MCT)-induced pulmonary hypertension models, TB-500/Tβ4 has been studied for its potential influence on the Notch3–Col3A–CTGF axis, with data suggesting a reduction in right ventricular hypertrophy in treated mice.(7)
Broader cardiac research indicates that Tβ4/TB-500 may:
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Improve myocardial cell survival under hypoxic conditions
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Promote angiogenesis in cardiac tissue
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Support reparative processes following coronary artery ligation(8,9)
In mouse heart injury models, TB-500 has been associated with:
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Activation of integrin-linked kinase (ILK) and Akt signaling
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Enhanced early survival of cardiomyocytes
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Improved myocardial function metrics
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Increased migration of myocardial and endothelial cells in fetal hearts, with similar behaviors observed in adult cardiomyocytes
These data have led investigators to explore TB-500 in combination with cardiac reprogramming strategies for potential synergistic effects in heart tissue repair.(8,9)
5. TB-500 and Hair Follicle Activity
Studies in murine models examined TB-500’s potential influence on hair growth.(10)
Reported outcomes:
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Increased number of hair shafts and hair follicles on histologic analysis
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Elevated mRNA and protein levels of specific molecular markers in TB-500–treated mice
These changes were associated with a notable stimulation of hair growth in treated animals, suggesting a possible role for TB-500/Tβ4 in hair follicle cycling and regeneration within experimental models.
6. TB-500 and Angiogenesis / Blood Vessel Formation
Work in human umbilical vein endothelial cells (HUVECs) and murine critical limb ischemia (CLI) models explored the proangiogenic potential of TB-500.(13)
Key findings included:
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Enhanced HUVEC viability, migration, and tube formation
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Upregulated expression of angiogenesis-related markers:
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Ang2 (angiopoietin-2)
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Tie2 (TEK receptor)
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VEGFA
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CD31 and α-SMA in tissue
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Activation of Notch/NF-κB pathway components:
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NOTCH1 intracellular domain (N1ICD)
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Notch3
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NF-κB and phosphorylated p65 (p-p65)
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When pathway inhibitors such as DAPT (Notch inhibitor) and BMS (NF-κB pathway modulator) were introduced, they appeared to blunt TB-500’s observed effects on angiogenesis, suggesting that TB-500 may exert its proangiogenic potential—at least in part—via these signaling pathways.
7. TB-500 and Corneal Tissue
Ophthalmic models have evaluated TB-500/Tβ4 in corneal wound healing and inflammation.(14)
Experimental observations include:
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Increased expression of IL-1β and IL-6 mRNA in corneal tissue shortly after injury
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Decreased levels of neutrophil chemoattractants (MIP-2 and KC) after alkali injury, potentially reducing polymorphonuclear neutrophil (PMN) infiltration
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Suggested modulation of NF-κB signaling pathways and downstream inflammatory cascades
Additionally, TB-500 overexpression in certain cell models has been associated with:
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Increased cell proliferation rates
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Reduced basal apoptosis
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Resistance to pro-apoptotic stimuli
In corneal epithelial cells, TB-500 is hypothesized to:
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Inhibit caspase activation
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Limit mitochondrial release of pro-apoptotic proteins
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Promote survival signaling via Akt, possibly in conjunction with PINCH and integrin-linked kinase (ILK)
While these mechanisms remain under active investigation, they collectively suggest potential cytoprotective and anti-apoptotic features in corneal and epithelial models.
Research-Use Only Disclaimer
TB-500 from OptiBuild Peptides is provided exclusively for laboratory, scientific, and in-vitro research purposes.
It is not intended for human or veterinary use, medical treatment, or diagnostic applications.
All purchasers are expected to comply with our Terms and Conditions and all applicable regulations.
References
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Kleinman HK, Sosne G. Thymosin β4 Promotes Dermal Healing. Vitam Horm. 2016;102:251-75. doi: 10.1016/bs.vh.2016.04.005. Epub 2016 May 24.
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Ho EN, Kwok WH, Lau MY, Wong AS, Wan TS, Lam KK, Schiff PJ, Stewart BD. 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. J Chromatogr A. 2012 Nov 23;1265:57-69.
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Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature. 2008 May 15;453(7193):314-21.
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Santra M, et al. Thymosin β4 up-regulation of microRNA-146a promotes oligodendrocyte differentiation and suppression of the Toll-like proinflammatory pathway. J Biol Chem. 2014;289(28):19508–19518.
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Malinda KM, et al. Thymosin β4 Accelerates Wound Healing. J Invest Dermatol. 1999;113(3):364-368.
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Treadwell T, et al. The regenerative peptide thymosin β4 accelerates the rate of dermal healing in preclinical animal models and in patients. Ann N Y Acad Sci. 2012.
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Wei C, Kim IK, Li L, Wu L, Gupta S. Thymosin Beta 4 protects mice from monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy. PLoS One. 2014;9(11):e110598.
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Srivastava D, Ieda M, Fu J, Qian L. Cardiac repair with thymosin β4 and cardiac reprogramming factors. Ann N Y Acad Sci. 2012;1270:66–72.
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Bock-Marquette I, et al. Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature. 2004;432(7016):466–472.
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Gao Xy, Hou F, Zhang Zp, et al. Role of thymosin beta 4 in hair growth. Mol Genet Genomics. 2016;291:1639–1646