Thymosin Beta-4
low riskAlso: TB-4 · Tβ4 · Thymosin β4 · LKKTETQ (active fragment)
Thymosin Beta-4 (TB-4) is a naturally occurring 43-amino-acid peptide found in virtually all human and animal cells, with highest concentrations in platelets, white blood cells, and wound fluid. It is a master regulator of actin polymerization and plays central roles in cell migration, angiogenesis, and tissue repair. TB-4 is the full native protein. TB-500 — commonly confused with TB-4 — is a synthetic peptide fragment (Ac-LKKTETQ) derived from the actin-binding region of TB-4, not the full molecule.
Reported Benefits
Wound healing
TB-4 accelerates wound healing in animal models and has completed Phase II trials for chronic dermal ulcers (RegeneRx). Human stasis ulcer trials showed statistically significant improvement.
Cardiac protection and repair
Animal models show reduced infarct size and improved cardiac function post-MI. Phase II trials for acute MI have been conducted.
Corneal healing
Phase II clinical trials (RegeneRx RGN-259 eye drops) demonstrated statistically significant improvements in dry eye and neurotrophic keratopathy.
Anti-inflammatory and immune modulation
TB-4 reduces TNF-α and IL-1β in animal inflammatory models; mechanism involves downregulation of NF-κB.
Tendon and musculoskeletal repair
Animal data show improved tendon healing; extrapolated widely in performance recovery contexts without direct human RCT support.
Mechanism of Action
TB-4 sequesters G-actin, regulating actin dynamics and cytoskeletal organization. It promotes cell migration via integrin-linked kinase (ILK), stimulates angiogenesis through upregulation of VEGF and laminin-5, reduces inflammation via NF-κB inhibition, and promotes keratinocyte and endothelial cell migration in wound beds.
Key Clinical Studies
Guarnera et al. (2008)
Phase II, randomized, double-blind · 74
TB-4 topical gel significantly improved healing of chronic venous stasis ulcers vs. placebo
Ruff et al. (2010)
Phase II, randomized, double-blind · 36
IV TB-4 showed safety and possible efficacy signals in acute MI, but trial was underpowered
Overview and the TB-4 vs. TB-500 Distinction
Thymosin Beta-4 and TB-500 are frequently conflated, but they are different compounds. TB-4 refers to the full 43-amino-acid native peptide produced endogenously in human cells. TB-500 is a synthetic peptide corresponding only to the actin-binding region of TB-4 (the tetrapeptide sequence Ac-Lys-Lys-Thr-Glu-Thr-Gln, or LKKTETQ), developed to isolate that specific functional domain in a more stable, manufacturable form. Most commercially available “TB-500” is this fragment, not the full TB-4 protein. TB-4 has undergone clinical development by RegeneRx Biopharmaceuticals; TB-500 has not been studied in human trials.
Evidence Summary
TB-4 has more human clinical data than almost any research peptide, largely due to RegeneRx’s Phase II trials in wound healing, acute MI, and dry eye disease. Results have been positive but studies remain small, and no Phase III trials have been completed or approved. The full TB-4 protein is what was studied clinically; practitioners using TB-500 are working with a fragment whose standalone efficacy in humans is not separately established.
Regulatory Status
TB-4 is not FDA-approved as a drug. It has been studied under IND (investigational new drug) protocols by RegeneRx. TB-500 is classified as a research peptide and is not available through US compounding pharmacies for human use. Both are for research purposes only in the US.
Most Common Use Cases
In research contexts, TB-4 is used for musculoskeletal injuries (tendons, ligaments, muscle tears), post-surgical recovery, and inflammatory conditions. The cardiac and ocular applications come from the clinical trial literature. TB-500, often sold and used interchangeably with TB-4, is primarily used for sports injury recovery and wound healing in performance medicine settings.
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Regulatory Status
Research OnlySafety Profile
Side Effects
- •Injection site irritation
- •Transient fatigue
- •Mild nausea (rare)
Contraindications
- •Active malignancy (promotes angiogenesis)
- •Pregnancy
Drug Interactions
- •Anticoagulants (theoretical interaction via platelet activity)
Primary Uses
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