Research Profile — Healing and Regeneration Research

TB-500 (Thymosin Beta-4): Complete Research Profile

Tβ4Timbetasin

TB-500 is the synthetic form of Thymosin Beta-4, a naturally occurring 43-amino-acid protein found in nearly all human and animal cells. It is the primary actin-sequestering protein in eukaryotic cells, playing a fundamental role in cell motility, migration, and cytoskeletal organization. The protein regulates the balance between monomeric G-actin and filamentous F-actin, which is central to cellular movement and tissue repair processes. Research interest in TB-500 spans wound healing, cardiac repair, anti-inflammatory mechanisms, hair follicle regeneration, and corneal healing. Its large molecular size (4963 Da) and multi-domain structure enable interactions with multiple biological targets simultaneously.

Technical Specifications

CAS Number	77591-33-4
Molecular Formula	C212H350N56O78S
Molecular Weight	4963.44 g/mol
Amino Acids	43
Sequence	Ac-SDKPDMAEIEKFDKSKLKKTETQEKNPLPSKETIEQEKQAGES
Purity	≥99% (HPLC)
Appearance	White lyophilized powder
Salt Form	Acetate
Solubility	Soluble in water
Storage	-20°C lyophilized, 2-8°C reconstituted

Origin & Discovery

TB-500 is a synthetic version of Thymosin Beta-4, a 43-amino-acid protein originally isolated from the thymus gland. Thymosin Beta-4 is one of the most abundant intracellular proteins and is found in virtually all cell types except red blood cells. It was first characterized in the 1960s by Allan Goldstein's research group at the Albert Einstein College of Medicine.

Mechanism of Action

TB-500 exerts its biological effects primarily through regulation of the actin cytoskeleton, the structural framework that governs cell shape, movement, and division. Actin Sequestration: TB-500 is the primary G-actin sequestering protein in cells. It binds monomeric globular actin (G-actin) with a 1:1 stoichiometry, regulating its polymerization into filamentous actin (F-actin). This balance between G-actin and F-actin is critical for cell migration, as cells must dynamically reorganize their cytoskeleton to move through tissue. LKKTETQ Active Domain: The actin-binding domain of TB-500 resides at amino acids 17-23, corresponding to the sequence LKKTETQ. This central domain is responsible for the actin-sequestering activity and has been shown to be sufficient for many of TB-500's observed biological effects in isolation. Cell Migration: By regulating actin dynamics, TB-500 promotes the migration of endothelial cells, keratinocytes, and other cell types to wound sites. This is particularly relevant in wound healing, where cell migration to the injury site is rate-limiting for tissue repair. NF-κB Downregulation: TB-500 has been shown to downregulate Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB), a central transcription factor in inflammatory signaling. This anti-inflammatory mechanism operates independently of its actin-related functions and may contribute to its observed effects in inflammatory models. Metalloproteinase Regulation: TB-500 modulates matrix metalloproteinase (MMP) activity, enzymes that degrade extracellular matrix components during tissue remodeling. Balanced MMP activity is essential for orderly wound healing and prevention of excessive scarring.

Wound Healing & Cell Migration

TB-500's wound healing effects are among its best-characterized properties. Malinda et al. (1999) demonstrated that Thymosin Beta-4 promoted dermal wound repair in rats, with accelerated wound closure, enhanced collagen deposition, and increased angiogenesis at the wound site. Sosne et al. (2002) extended these findings to corneal wound healing, showing accelerated re-epithelialization in corneal injury models. In a landmark study published in Nature, Bock-Marquette et al. (2004) demonstrated that Thymosin Beta-4 promoted cardiac cell migration and survival after myocardial infarction, activating the integrin-linked kinase (ILK)/Akt signaling pathway. This cardiac repair finding significantly expanded research interest in TB-500 beyond dermal wound healing.

Citations

Malinda KM, et al. (1999) "Thymosin Beta-4 accelerates wound healing." J Invest Dermatol, 113(3), 364-368.
Sosne G, et al. (2002) "Thymosin Beta-4 promotes corneal wound healing." Invest Ophthalmol Vis Sci, 43(7), 2163-2169.
Bock-Marquette I, et al. (2004) "Thymosin Beta-4 activates integrin-linked kinase and promotes cardiac cell migration." Nature, 432(7016), 466-472.

Anti-Inflammatory Effects

The anti-inflammatory properties of TB-500 have been documented in multiple tissue systems. Sosne et al. (2007) showed that Thymosin Beta-4 reduced inflammatory cytokine production in corneal epithelial cells exposed to inflammatory stimuli. Qiu et al. (2011) published in FASEB Journal that TB-500 reduced TNF-alpha-induced NF-κB activation in corneal epithelial cells, identifying a key molecular mechanism for its anti-inflammatory effects. These findings suggest that TB-500's tissue-protective effects involve both enhanced repair (via actin regulation) and reduced inflammatory damage (via NF-κB suppression), a dual mechanism that may explain its broad applicability across tissue types.

Citations

Sosne G, et al. (2007) "Thymosin Beta-4 anti-inflammatory effects." Expert Opin Biol Ther, 7(11), 1611-1615.
Qiu P, et al. (2011) "TB-500 reduces NF-κB activation." FASEB J, 25(12), 4487-4498.

Tendon & Musculoskeletal Repair

Seiwerth et al. (2018) reviewed the evidence for TB-500 in musculoskeletal repair contexts, noting that Thymosin Beta-4 enhanced tendon healing through improved collagen organization, increased tenocyte migration, and modulated inflammatory responses at the injury site. The protein's role in promoting organized collagen deposition rather than disorganized scar tissue is of particular interest in tendon research, where functional recovery depends on the alignment and mechanical properties of repaired tissue.

Citations

Seiwerth S, et al. (2018) "TB-500 and musculoskeletal repair review."

Frequently Asked Questions

What is TB-500?▼

TB-500 is the synthetic form of Thymosin Beta-4, a 43-amino-acid protein originally isolated from the thymus gland. It is the primary actin-sequestering protein in eukaryotic cells and is studied for wound healing, anti-inflammatory, and tissue repair applications in research settings.

What is the difference between TB-500 and Thymosin Beta-4?▼

TB-500 and Thymosin Beta-4 (Tβ4) refer to the same amino acid sequence. TB-500 is the common research designation for the synthetic version of the naturally occurring Thymosin Beta-4 protein.

How does TB-500 differ from BPC-157?▼

TB-500 (43 amino acids, MW 4963) works primarily through actin regulation and NF-κB suppression. BPC-157 (15 amino acids, MW 1420) works through VEGFR2 activation and FAK-paxillin signaling. They target different pathways but are both studied in regenerative research.

What is the molecular weight of TB-500?▼

TB-500 has a molecular weight of 4963.44 g/mol and consists of 43 amino acids with the molecular formula C212H350N56O78S.