Thymosin Beta-4: Full Research Profile

Your body already makes one of the most studied regenerative peptides in modern science. Thymosin beta-4 (abbreviated TB-4 or Tb4) is a 43-amino-acid peptide present in nearly every human cell. First isolated from calf thymus tissue in the 1960s, it spent decades as a footnote in immunology textbooks before researchers discovered something remarkable: this small protein appeared to orchestrate tissue repair across virtually every organ system studied, from the heart and brain to the cornea and skin.

That discovery set off a wave of preclinical and clinical research that continues today. RegeneRx Biopharmaceuticals has advanced TB-4-based eye drops through Phase 3 clinical trials. Animal studies show it can reduce brain damage after traumatic injury, restart dormant cardiac repair programs, and accelerate wound closure. It also sits at the center of one of the biggest doping scandals in professional sports history.

This profile covers everything the research tells us about thymosin beta-4: what it does at the molecular level, what the clinical evidence actually shows, where it overlaps with (and differs from) the popular synthetic fragment TB-500, and the unresolved questions that still surround it, including the cancer debate.

Quick Facts

Property	Detail
Full name	Thymosin beta-4 (Tb4, TMSB4X)
Type	Naturally occurring endogenous peptide
Amino acids	43 (sequence: Ac-SDKPDMAEIEKFDKSKLKKTETQEKNPLPSKETIEQEKQAGES)
Molecular weight	~4,921 Da
Gene	TMSB4X (X-linked, with Y-chromosome homolog TMSB4Y)
Found in	Nearly all human cells except red blood cells; also present in tears, saliva, wound fluid, and cerebrospinal fluid
Primary intracellular role	G-actin sequestration (cytoskeleton regulation)
Research applications	Wound healing, cardiac repair, corneal healing, neuroprotection, hair growth, anti-fibrosis
FDA status	Not approved; RGN-259 eye drops in Phase 3 trials
WADA status	Prohibited (S2 category: Peptide Hormones and Growth Factors)

What Is Thymosin Beta-4?

Thymosin beta-4 is the most abundant member of the beta-thymosin family, a group of small peptides first discovered in thymus extracts by Allan Goldstein and colleagues in the 1960s. Despite the name, TB-4 is not limited to the thymus. It exists in virtually every nucleated cell in the body, typically at concentrations around 0.1-0.5 mM, making it one of the most plentiful peptides in mammalian tissues.

The peptide is encoded by the TMSB4X gene on the X chromosome. It is water-soluble, has no stable folded structure in solution (scientists call these "intrinsically unstructured proteins"), and gains specific shapes only when it binds to partner molecules. This structural flexibility is part of what makes it so versatile — the same peptide can interact with different proteins to trigger different effects depending on the cellular context.

Inside cells, TB-4's primary job is managing the actin cytoskeleton. Actin makes up roughly 10% of the total protein in most cells and is the structural scaffolding that determines cell shape and drives cell movement. TB-4 binds to individual actin monomers (called G-actin) and prevents them from assembling into filaments. This "sequestering" function is essential for normal cell behavior: it maintains a reserve pool of actin building blocks that cells can deploy rapidly when they need to move, divide, or change shape.

But TB-4 does far more than manage actin. Researchers now recognize that many of its effects on tissue repair, inflammation, and cell survival cannot be explained by actin binding alone. The peptide appears to interact with multiple other molecular partners through what scientists call "protein moonlighting" — one protein performing several unrelated functions. This helps explain why TB-4 research spans such a wide range of therapeutic areas.

TB-4 vs. TB-500: Understanding the Difference

This is one of the most important distinctions in the peptide space, and one that vendors and online forums regularly blur. TB-4 and TB-500 are related but structurally and functionally distinct compounds.

Thymosin beta-4 (TB-4) is the full-length, naturally occurring 43-amino-acid peptide. Every clinical trial, every Phase 3 study, every regulatory submission to the FDA has used the complete TB-4 molecule.

TB-500 is a synthetic 7-amino-acid fragment that corresponds to positions 17-23 of the TB-4 sequence. Its sequence is Ac-LKKTETQ. It weighs roughly 889 Da — about one-fifth the size of the full peptide.

Here is what this means in practice:

Feature	Thymosin Beta-4 (TB-4)	TB-500
Length	43 amino acids	7 amino acids
Molecular weight	~4,921 Da	~889 Da
Origin	Naturally occurring	Synthetic fragment
Clinical trials	Yes (Phase 1-3 completed)	None in humans
Active domain	Full peptide with multiple functional regions	Actin-binding motif only
FDA investigation	RGN-259 in clinical development	No clinical development

The LKKTETQ sequence is the actin-binding motif of TB-4 and is strongly conserved across all beta-thymosins. Studies confirm this fragment retains some of TB-4's activities — it can promote cell migration, bind actin, and accelerate wound healing in animal models. But TB-4 contains additional functional domains that TB-500 lacks, including the N-terminal region involved in activating terminal deoxynucleotidyl transferase and the Ac-SDKP sequence with potent anti-fibrotic properties.

The bottom line: all clinical evidence comes from the full TB-4 peptide. TB-500 may share some of those properties, but claiming equivalence between the two is not supported by the research. For a detailed look at the fragment, see our dedicated TB-500 profile.

Key Fragments: Ac-SDKP and LKKTETQ

TB-4 has two biologically active fragments that have attracted significant research attention on their own.

Ac-SDKP (N-acetyl-seryl-aspartyl-lysyl-proline) comes from the first four amino acids of the TB-4 sequence. The body produces it naturally by cleaving TB-4 with two enzymes: meprin-alpha first cuts the peptide into intermediate fragments, then prolyl oligopeptidase (POP) releases the Ac-SDKP tetrapeptide. This fragment is primarily cleared by angiotensin-converting enzyme (ACE), specifically its N-domain active site. This is one reason ACE inhibitors raise Ac-SDKP levels in patients — they block its degradation.

Ac-SDKP has shown strong anti-fibrotic properties across multiple organ systems, including the heart, lungs, kidneys, and liver. In animal models, it both prevents and reverses fibrosis by reducing the conversion of fibroblasts to myofibroblasts, lowering TGF-beta signaling, and decreasing inflammatory cell infiltration.

LKKTETQ (positions 17-23) is the actin-binding motif that TB-500 replicates. This fragment drives cell migration, actin dynamics, and many of TB-4's wound-healing effects. Research confirms it is active in promoting dermal healing, angiogenesis, and cell movement.

Understanding these fragments matters because it shows that TB-4 is not a single-function molecule. Different regions of the peptide drive different biological effects, which is partly why the full-length version has a broader therapeutic profile than any individual fragment.

Mechanism of Action

TB-4 operates through several interconnected pathways. Here is what the research has identified:

Actin Sequestration and Cell Migration

TB-4 is the principal G-actin-sequestering molecule in mammalian cells. By binding actin monomers and controlling when and where they polymerize into filaments, TB-4 directly regulates cell migration. When tissue is damaged, migrating cells need rapid cytoskeletal reorganization to reach the injury site. TB-4 facilitates this by managing the available pool of actin building blocks.

Anti-Inflammatory Signaling

TB-4 reduces inflammation through multiple routes. It decreases NF-kB transcription, lowering the production of pro-inflammatory cytokines. It reduces polymorphonuclear leukocyte infiltration at wound sites. It also shifts macrophage polarization, decreasing pro-inflammatory M1 macrophages while preserving anti-inflammatory M2 populations. (For another peptide with strong anti-inflammatory and immune-modulating properties, see our profile on LL-37.)

Angiogenesis

TB-4 promotes the formation of new blood vessels by stimulating endothelial cell migration and upregulating vascular endothelial growth factor (VEGF). This is important for tissue repair because new blood supply is essential for delivering oxygen and nutrients to healing tissue.

Cell Survival (Anti-Apoptosis)

TB-4 forms a complex with PINCH-1 and integrin-linked kinase (ILK), which activates the survival kinase Akt (protein kinase B). This pathway protects cells from apoptosis (programmed cell death) under stress conditions, including oxidative stress after ischemic injury. TB-4 also upregulates anti-oxidative enzymes and anti-apoptotic genes.

Stem/Progenitor Cell Activation

One of TB-4's most striking properties is its ability to activate endogenous stem and progenitor cells. In the heart, it can reactivate embryonic developmental programs in adult cardiac tissue. In the brain, it promotes neurogenesis. In hair follicles, it mobilizes follicular stem cells. This capacity to "remind" adult tissues of their developmental potential is unusual and is a major focus of ongoing research.

Extracellular Matrix Remodeling

TB-4 regulates matrix metalloproteinases (MMPs), the enzymes that break down and reorganize the extracellular matrix during tissue repair. It increases MMP-2 production while helping balance MMPs and their tissue inhibitors (TIMPs), promoting organized tissue remodeling rather than disorganized scarring.

Research Evidence by Area

Wound Healing and Tissue Repair

Wound healing was the first therapeutic application explored for TB-4, and it remains the area with the most extensive evidence.

In preclinical studies, TB-4 consistently accelerates wound closure across multiple models. One study using recombinant human TB-4 demonstrated it promotes full-thickness cutaneous wound healing in BALB/c mice. The peptide works through several simultaneous mechanisms: improved re-epithelialization, increased vascular density at the wound site, reduced inflammation, and accelerated tissue remodeling.

Notably, TB-4 reduces scar formation. It decreases the number of myofibroblasts in healing wounds, which are the cells responsible for excessive collagen deposition and fibrosis. This anti-scarring effect sets it apart from many growth factors that accelerate healing but often produce more scarring.

The peptide has also shown effectiveness in challenging wound models, including diabetic wounds and burns. Diabetic wounds heal poorly because of compromised blood supply and impaired cell migration — two problems that TB-4 directly addresses.

For readers interested in how TB-4 compares to other healing peptides, see our profiles on BPC-157 and GHK-Cu, both of which are also studied for tissue repair but work through different mechanisms.

Cardiac Repair

The cardiac research on TB-4 may be the most scientifically remarkable. In 2004, Deepak Srivastava's lab at the Gladstone Institutes demonstrated something previously thought impossible: TB-4 could reactivate the embryonic cardiac developmental program in adult mouse hearts.

When researchers ligated (tied off) coronary arteries in mice to simulate a heart attack and then administered TB-4 systemically, the peptide:

Reduced myocardial cell death by activating the ILK/Akt survival pathway
Stimulated new blood vessel growth through coronary vasculogenesis
Activated endogenous cardiac progenitor cells, prompting them to differentiate into functional heart muscle
Reduced infarct size and fibrosis through antifibrotic and proangiogenic activity

TB-4 was described as "the first known molecule able to initiate simultaneous myocardial and vascular regeneration after systemic administration in vivo." This is significant because most cardiac repair strategies target either blood vessel growth or muscle regeneration, not both at once.

The Ac-SDKP fragment of TB-4 adds another layer to the cardiac story. In spontaneously hypertensive rats, Ac-SDKP treatment decreased collagen content and collagen volume fraction in the left ventricle. In heart failure models, it both prevented and reversed myocardial fibrosis while reducing mortality after acute myocardial infarction.

However, the picture is not entirely positive. A study in pigs found that systemic dosing of TB-4 before and after ischemia did not attenuate global myocardial ischemia-reperfusion injury. The larger animal model may require different dosing strategies, or TB-4's cardiac benefits may be more pronounced in certain injury patterns than others.

TB-4 is also elevated in women with heart failure with preserved ejection fraction, according to research published in the Journal of the American Heart Association. Whether this elevation is protective, compensatory, or pathological remains an open question.

Corneal and Eye Healing

Eye healing is where TB-4 is closest to becoming an approved drug. RegeneRx Biopharmaceuticals has developed RGN-259, a preservative-free 0.1% thymosin beta-4 ophthalmic solution, and advanced it through multiple clinical trials.

Neurotrophic keratopathy (NK) is a degenerative corneal disease caused by impaired corneal nerve function. In the Phase 3 SEER-1 trial, 60% of patients treated with RGN-259 achieved complete corneal healing after four weeks of treatment, compared to just 12.5% of placebo-treated patients. The healed corneas also maintained their integrity two weeks after treatment stopped, while the single healed placebo patient relapsed. Two additional confirmatory Phase 3 trials (SEER-2 and SEER-3) are being conducted simultaneously in the U.S. and Europe. RGN-259 has received orphan drug designation for NK in the United States.

Dry eye syndrome is the other major ophthalmic target. In the Phase 3 ARISE trials, RGN-259 was tested in approximately 600 patients with dry eye. Preclinical comparisons showed RGN-259 performed equal to or better than cyclosporine A (Restasis), lifitegrast (Xiidra), and diquafosol (Diquas) after ten days of treatment — established prescription drugs that represent the current standard of care.

The mechanism in the eye involves promoting corneal re-epithelialization, dampening inflammation, reducing polymorphonuclear leukocyte infiltration, and regulating the balance of matrix metalloproteinases and tissue inhibitors. To date, over 1,700 subjects have received RGN-259, and the drug has been well tolerated with no documented side effects matching those of existing approved products.

Neurological Repair

TB-4 is widely distributed throughout the central nervous system, and its neuroprotective and neurorestorative properties are an active area of investigation. The research here is entirely preclinical but consistently promising.

Traumatic brain injury (TBI): In rat models, TB-4 treatment initiated 6 hours after controlled cortical impact reduced cortical lesion volume by 20-30% (dose-dependent) and reduced hippocampal cell loss. Treated animals showed significant improvement in spatial learning, reduced forelimb and hindlimb footfaults, and better neurological severity scores. Even when treatment was delayed to 24 hours post-injury — past the window where neuroprotective strategies are effective — TB-4 still reduced hippocampal cell loss, boosted angiogenesis and neurogenesis, increased oligodendrogenesis, and improved functional recovery.

This delayed treatment window is important. Most neuroprotective drugs must be given within minutes to hours of injury, before cells die. TB-4 appears to work through neurorestorative mechanisms (promoting new cell growth and tissue remodeling) rather than purely neuroprotective ones (preventing cell death), giving it a wider therapeutic window.

Stroke: TB-4 improved neurological functional outcomes in a rat model of embolic stroke when administered 24 hours after the event, with an optimal dose of 3.75 mg/kg.

Multiple sclerosis: The peptide showed benefits in a mouse model of MS, likely through its ability to promote oligodendrogenesis — the generation of new oligodendrocytes, the cells that produce myelin sheaths around nerve fibers.

Blood-brain barrier protection: A 2025 study published in Scientific Reports demonstrated that TB-4 protects brain microvascular endothelial cells from hypoxia-induced dysfunction through S1PR1-dependent mechanisms.

The mechanisms driving these neurological effects include promoting neural stem cell migration and differentiation, stimulating axonal regrowth, supporting synaptogenesis, and reducing neuroinflammation. For other peptides with neurological research interest, see our profiles on Semax and Selank.

Hair Growth

TB-4's effect on hair growth was discovered somewhat serendipitously during wound-healing studies in rodents. Researchers noticed that treated animals grew hair faster and more densely around wound sites.

The foundational study by Philp et al. (2004), published in The FASEB Journal, established that TB-4 stimulates hair growth in normal rats and mice. A specific subset of hair follicular keratinocytes was found to express TB-4 in a coordinated pattern during the hair growth cycle.

How does it work? TB-4 appears to promote hair growth through at least four mechanisms:

Stem cell activation: TB-4 mobilizes hair follicle stem cells, promoting their migration to the base of the follicle and subsequent differentiation
Angiogenesis: The peptide stimulates VEGF expression, improving blood supply to hair follicles through perifollicular vascularization
Matrix remodeling: TB-4 increases MMP-2 secretion, helping remodel the extracellular matrix around follicles
Wnt signaling: TB-4 appears to regulate VEGF and MMP-2 levels through the Wnt/beta-catenin/Lef-1 pathway, a signaling cascade central to hair follicle development

Transgenic mice overexpressing TB-4 showed accelerated hair growth, while TB-4 knockout mice had reduced VEGF expression in skin. Topical application increased anagen-phase (actively growing) hair follicles approximately twofold within seven days. However, the effect reversed within 14 days of stopping treatment, suggesting TB-4 maintains rather than permanently changes follicle behavior.

Despite strong preclinical evidence, there are no published human clinical trials for TB-4 in hair loss treatment. This remains an area awaiting clinical translation.

Anti-Fibrotic Effects

Fibrosis — excessive scar tissue formation — is a feature of chronic disease in the heart, lungs, liver, and kidneys. The Ac-SDKP fragment derived from TB-4 has emerged as one of the most promising anti-fibrotic agents in preclinical research.

The Tb4-POP-Ac-SDKP axis (where prolyl oligopeptidase cleaves TB-4 to release Ac-SDKP) represents a natural anti-fibrotic pathway in the body. Research shows this pathway is downregulated in advanced chronic heart failure in both patients and animal models, suggesting its failure may contribute to disease progression.

Ac-SDKP prevents and reverses fibrosis by:

Blocking TGF-beta-induced fibroblast-to-myofibroblast conversion
Reducing inflammatory mediators and macrophage infiltration
Modulating MEK-ERK signaling pathways
Promoting normally aligned collagen fiber production rather than disorganized scar tissue

This research has implications beyond TB-4 as a therapeutic. Since ACE inhibitors raise Ac-SDKP levels by blocking its degradation, some of the anti-fibrotic benefits attributed to ACE inhibitors may actually work through this TB-4 fragment pathway.

Clinical Trials

TB-4 has been through a more extensive clinical trial program than many peptides in the research space. Here is a summary of the formal clinical evidence:

Phase 1 Safety Studies

Intravenous study in healthy volunteers: Four dose cohorts (42, 140, 420, and 1,260 mg) received single and then daily IV doses for 14 days. No dose-limiting toxicities or serious adverse events were observed. The pharmacokinetic profile showed dose-proportional responses.

Recombinant human TB-4 (NL005) study in Chinese volunteers: Seven ascending single-dose cohorts (0.05 to 25.0 micrograms/kg IV) and three multiple-dose cohorts (0.5, 2.0, and 5.0 micrograms/kg daily for 10 days). All adverse events were mild to moderate. No dose-limiting toxicities, no serious adverse events, and no tumorigenesis observed within 6 months.

Phase 2 Trials

TB-4 was tested in patients with pressure ulcers, venous stasis ulcers, and epidermolysis bullosa. In these wound-healing trials, TB-4 accelerated the rate of repair while proving safe and well tolerated.

Phase 3 Trials (Ophthalmology)

SEER-1 (Neurotrophic keratopathy): 60% complete corneal healing with RGN-259 vs. 12.5% with placebo. Healing was maintained after treatment cessation.

SEER-2 and SEER-3 (Neurotrophic keratopathy): Confirmatory Phase 3 trials enrolling approximately 70 patients each, conducted in the U.S. and Europe. Currently ongoing.

ARISE-1 and ARISE-2 (Dry eye syndrome): Phase 2b/3 and Phase 3 trials enrolling approximately 600 patients testing RGN-259 eye drops.

Acute myocardial infarction (NL005): A safety and efficacy Phase 2 trial of recombinant human TB-4 (NCT05485818) for acute MI patients has been registered.

All clinical development work is being conducted by RegeneRx Biopharmaceuticals and its joint venture partner ReGenTree LLC (with HLB Therapeutics).

Safety and Side Effects

TB-4 has one of the more thoroughly documented safety profiles among research peptides, though important gaps remain.

Preclinical safety: Twenty-three non-clinical studies have been completed, demonstrating the safety of TB-4 for its intended clinical uses. No preclinical toxicology concerns were identified. The peptide is naturally present throughout the body, which provides a baseline safety argument that fully synthetic compounds lack.

Clinical safety: Across Phase 1 and Phase 2 trials, TB-4 has been well tolerated. Adverse events were generally mild and self-limiting. No dose-limiting toxicities or serious adverse events have been reported. Over 1,700 subjects have received RGN-259 (the ophthalmic formulation) across various trials.

Reported side effects from clinical and clinical-practice settings include:

Injection site reactions (redness, mild swelling, pain) — most common
Mild fatigue
Headache
Temporary mood changes
Rare: fever, skin rash, muscle aches

Important limitations: Long-term safety data beyond 6 months of follow-up remains limited. The cancer question (discussed below) represents a genuine area of uncertainty. Safety in pediatric populations has not been established.

For context on how this safety profile compares to other peptides, see our guide to Thymosin Alpha-1, a related thymosin-family peptide with a longer clinical track record.

The Cancer Question

This is the most contentious area in TB-4 research, and it deserves a careful, balanced treatment.

The concern: TB-4 is overexpressed in many solid tumors. Higher levels of TB-4 have been found in cancerous tissue from patients with colon cancer, pancreatic cancer, non-small cell lung cancer, melanoma, head and neck squamous cell carcinoma, and renal cell carcinoma. In these cancers, elevated TB-4 expression is associated with increased metastasis, angiogenesis, chemotherapy resistance, and poorer survival outcomes.

The evidence linking TB-4 to tumor progression:

In mice injected with TB-4-expressing melanoma cells, the average number of metastatic lung nodules was 46.7 vs. 10.9 in controls — a roughly fourfold increase
TB-4 overexpression in colon cancer cells made them more resistant to both immune-mediated and chemotherapy-induced cell death
In pancreatic cancer, exogenous TB-4 stimulated proinflammatory cytokine secretion (IL-6, IL-8, MCP-1) and activated JNK signaling
TB-4 knockout melanoma cells showed dramatically reduced metastatic potential; restoring a downstream transcription factor (MRTF-A) fully restored their ability to metastasize

The counterargument:

In hematological malignancies (multiple myeloma, plasma cell leukemia), TB-4 expression is decreased relative to normal cells. Overexpressing TB-4 in myeloma cells actually reduced their proliferation and migration, increased their sensitivity to apoptosis, and extended survival in mouse models
The TB-4 gene knockout mouse develops normally, is fertile, and shows no obvious pathology, suggesting TB-4 is not required for tumor initiation
No tumorigenesis was observed in clinical trial subjects within 6 months of follow-up
TB-4 is naturally present at high concentrations throughout the body; whether elevated levels in tumors cause progression or are a response to tissue damage remains unresolved

The honest summary: The relationship between TB-4 and cancer is context-dependent and incompletely understood. The peptide's ability to promote cell migration, angiogenesis, and cell survival — the same properties that make it attractive for tissue repair — are also properties that tumors exploit. In most solid tumors studied, higher TB-4 expression correlates with worse outcomes. In some blood cancers, the opposite is true.

This does not mean TB-4 "causes" cancer. But it does mean that individuals with active malignancies or a high risk of cancer should approach TB-4 with caution, and that any future clinical development will need to carefully monitor for cancer-related outcomes. The question remains a legitimate area of scientific debate.

Legal and Regulatory Status

The regulatory picture for TB-4 is complex and has shifted significantly since 2023.

FDA status: TB-4 is not approved by the FDA for any therapeutic use. However, RegeneRx's RGN-259 eye drops are in active Phase 3 clinical development, and the formulation has received orphan drug designation for neurotrophic keratopathy.

Compounding restrictions: In October 2023, the FDA placed TB-4 (along with several other peptides) on the Category 2 list — "Bulk Drug Substances that Raise Significant Safety Risks." This effectively prohibits compounding pharmacies from producing TB-4 preparations under Section 503A regulations. When the FDA removed several other peptides from this list in September 2024, TB-4 remained restricted.

A complicating factor: the full 43-amino-acid TB-4 falls close to the molecular weight threshold where the FDA classifies compounds as biologics rather than drugs. This subjects it to stricter regulatory oversight than smaller peptides.

WADA status: TB-4 and TB-500 are both prohibited by the World Anti-Doping Agency under category S2 (Peptide Hormones, Growth Factors, Related Substances, and Mimetics). They have been banned since at least 2010. TB-500 is also prohibited in horse racing by the International Federation of Horseracing Authorities (IFHA) and the International Equestrian Federation (FEI).

Research chemicals: TB-4 and TB-500 products sold with "for research use only" or "not for human consumption" labels exist in a regulatory gray area. They are technically legal to purchase for research but illegal to market or sell for human therapeutic use. FDA enforcement in this area has been increasing since 2023, including warning letters to companies using social media influencers to imply therapeutic benefits.

The Essendon Doping Scandal

TB-4 entered mainstream public awareness through one of Australia's biggest doping controversies. Understanding this case illustrates the real-world regulatory and ethical issues surrounding peptide use in sports.

In 2012, the Essendon Football Club in the Australian Football League (AFL) ran a supplements injection program under biochemist Stephen Dank. The program involved several substances, including what was later determined to be thymosin beta-4, administered weekly for six weeks and then monthly.

In February 2013, the club self-reported to the AFL and the Australian Sports Anti-Doping Authority (ASADA). An independent review described "a disturbing picture of a pharmacologically experimental environment never adequately controlled or challenged or documented within the club."

Thirty-four players received show-cause notices. The AFL Anti-Doping Tribunal initially found them not guilty in March 2015, ruling that while TB-4 was a banned substance, there was insufficient evidence the players had actually received it. WADA appealed to the Court of Arbitration for Sport (CAS), which overturned the verdict in January 2016, finding it was "comfortably satisfied" the players were injected with thymosin beta-4. All 34 received two-year bans.

A notable detail: none of the players ever returned a positive drug test during 30 ASADA testing missions. The CAS verdict relied entirely on circumstantial evidence. Players had signed consent forms for "thymosin" injections, but the forms claimed the treatment was WADA-compliant. Stephen Dank received a lifetime ban.

The case cost Essendon over $5 million in legal and consulting fees, exclusion from the 2013 finals, a $2 million fine, and the loss of multiple draft picks.

Dosing in Research Settings

TB-4 has been studied at a range of doses across preclinical and clinical settings. This information is provided for research reference only; TB-4 is not approved for therapeutic use in humans.

Animal Research Doses

Model	Route	Dose	Schedule
Rat (stroke)	Intraperitoneal	2-18 mg/kg (optimal: 3.75 mg/kg)	Day 1, then every 3 days for 5 total doses
Rat (TBI)	Intraperitoneal	6-30 mg/kg	Starting 6-24 hours post-injury, daily for 3 days
Pig (cardiac)	Intravenous	6 mg/kg	Two doses (0 and 360 minutes)
Mouse (wound healing)	Topical	Various concentrations	Daily or tri-weekly application

Human Clinical Trial Doses

Study	Route	Dose	Schedule
Phase 1 (synthetic TB-4)	Intravenous	42-1,260 mg	Single dose, then daily for 14 days
Phase 1 (NL005)	Intravenous	0.05-25.0 mcg/kg	Single ascending doses; multiple doses daily for 10 days
Phase 3 (RGN-259)	Ophthalmic (eye drops)	0.1% solution	5 times daily for 4 weeks

A challenge for systemic TB-4 delivery is its short circulating half-life. The peptide is rapidly degraded in the bloodstream, which means maintaining effective blood concentrations requires either frequent dosing or alternative delivery methods — a problem researchers are actively working to solve.

Frequently Asked Questions

Is thymosin beta-4 the same as TB-500?

No. TB-4 is the full 43-amino-acid naturally occurring peptide. TB-500 is a synthetic 7-amino-acid fragment (Ac-LKKTETQ) representing only the actin-binding motif of TB-4. All clinical trial data comes from the full TB-4 molecule. TB-500 has no published human clinical trials. See our full TB-500 research profile for more details.

Both were originally isolated from thymus extracts, but they are structurally and functionally distinct peptides. Thymosin alpha-1 is a 28-amino-acid peptide primarily involved in immune modulation, with approved pharmaceutical products (Zadaxin) in some countries. TB-4 is a 43-amino-acid peptide with a broader range of tissue repair functions. They belong to different protein families despite sharing the "thymosin" name.

Can thymosin beta-4 cause cancer?

This is unresolved. TB-4 is overexpressed in many solid tumors and its tissue-repair properties (promoting cell migration, angiogenesis, and survival) are theoretically exploitable by cancer cells. However, it does not appear to initiate cancer in healthy tissue, and in some blood cancers it actually has tumor-suppressive effects. No tumorigenesis has been observed in clinical trial subjects. See The Cancer Question above for a detailed discussion.

Is thymosin beta-4 legal?

The legal status depends on context. It is not FDA-approved for any therapeutic use in the United States. Compounding pharmacies are prohibited from producing it following the FDA's 2023 Category 2 classification. It is banned by WADA in competitive sports. It can technically be sold as a research chemical with appropriate labeling, though enforcement has been increasing. RGN-259 (a TB-4 ophthalmic solution) is in active clinical development under FDA oversight.

How is thymosin beta-4 different from BPC-157?

BPC-157 is a 15-amino-acid synthetic peptide derived from a gastric protein, primarily studied for gastrointestinal healing and musculoskeletal repair. TB-4 is a 43-amino-acid naturally occurring peptide with broader tissue-repair applications spanning cardiac, corneal, neurological, and dermal healing. They work through different molecular mechanisms, though both promote angiogenesis and reduce inflammation. Some practitioners have explored combining them, but there is limited published research on that approach.

What is the connection to horse racing?

TB-500 was originally used in equine veterinary medicine to help prevent tendon adhesions and promote tissue recovery in racehorses. Reports of dramatic performance improvements led to its prohibition in horse racing. Racing authorities developed LC-MS analytical methods specifically to detect TB-500 and its metabolites in equine blood and urine. The detection threshold is 0.02 ng/mL in plasma and 0.01 ng/mL in urine.

Does thymosin beta-4 help with hair loss?

Animal studies consistently show TB-4 promotes hair growth by activating follicular stem cells, stimulating VEGF-mediated angiogenesis around follicles, and engaging Wnt/beta-catenin signaling. Topical application in mice doubled the number of actively growing hair follicles within seven days. However, no human clinical trials for hair loss have been published. The effect also appears to require ongoing treatment — hair follicles returned to baseline within two weeks of stopping TB-4 in animal studies.

The Bottom Line

Thymosin beta-4 is one of the most extensively studied regenerative peptides in the scientific literature. Its biology is genuinely remarkable — a single small protein that orchestrates wound healing, stimulates cardiac regeneration, protects neurons after brain injury, promotes corneal repair, and activates hair follicle stem cells. The breadth of its biological activity, driven by its structural flexibility and multiple functional domains, sets it apart from more narrowly targeted peptides.

The clinical evidence is strongest in ophthalmology, where Phase 3 trials for both neurotrophic keratopathy and dry eye syndrome have produced results that outperform existing prescription drugs. If RGN-259 receives FDA approval, it will be the first thymosin beta-4-based drug on the market and a validation of decades of research.

In other areas — cardiac repair, neuroprotection, wound healing, anti-fibrosis — the preclinical evidence is robust but the path to approved human therapies remains long. The cancer question adds genuine complexity to the risk-benefit calculation and will need careful, longitudinal data to resolve.

For now, TB-4 represents a peptide where the basic science is strong, the clinical pipeline is active, and the regulatory environment is restrictive. The gap between what animal studies show and what is available to patients is wide — but it is narrowing, one clinical trial at a time. For readers exploring the broader regenerative peptide space, our profiles on Epitalon and DSIP cover other peptides under investigation for longevity and recovery applications.

This article is for educational purposes only and does not constitute medical advice. Thymosin beta-4 is not FDA-approved for any therapeutic use. Consult a qualified healthcare provider before making any decisions about peptide therapies.

References and Further Reading:

Goldstein, A.L., et al. "Thymosin β4: a multi-functional regenerative peptide." Annals of the New York Academy of Sciences (2012). PubMed
Philp, D., et al. "Thymosin beta4 increases hair growth by activation of hair follicle stem cells." The FASEB Journal (2004). PubMed
Sosne, G., et al. "0.1% RGN-259 (Thymosin ß4) Ophthalmic Solution in Neurotrophic Keratopathy." PMC (2023). PMC
Xiong, Y., et al. "Neuroprotective and neurorestorative effects of thymosin beta4 treatment following experimental traumatic brain injury." PMC (2012). PMC
Bock-Marquette, I., et al. "Thymosin beta4 and cardiac repair." PubMed (2010). PubMed
Kassem, K.M., et al. "Tβ4–Ac-SDKP pathway: Any relevance for the cardiovascular system?" Canadian Journal of Physiology and Pharmacology (2019). PMC
Wang, J., et al. "Progress on the Function and Application of Thymosin β4." Frontiers in Endocrinology (2021). Frontiers
Ryu, Y.K., et al. "Thymosin Beta-4 Induces Mouse Hair Growth." PLOS One (2015). PLOS
Kim, S., et al. "Role of thymosin beta4 in tumor metastasis and angiogenesis." Journal of the National Cancer Institute (2003). Oxford Academic
Sribenja, S., et al. "Thymosin Beta 4 is Overexpressed in Human Pancreatic Cancer Cells." PMC (2010). PMC
Piao, Z., et al. "Thymosin beta 4 treatment improves left ventricular function after myocardial infarction." Translational Medicine Communications (2016). BMC
RegeneRx Biopharmaceuticals — corporate website for clinical trial updates
ClinicalTrials.gov NCT05485818 — TB-4 for acute myocardial infarction