TB-500 (Thymosin β4): Compound Profile

TB-500 is one of the most-marketed compounds in the research-peptide channel and one of the most casually misnamed. It is not, despite the trade name, a distinct molecule. The material sold under the label is — in every primary paper that defines it — synthetic thymosin β4 (Tβ4): a 43-amino-acid, N-terminally acetylated peptide that was sequenced by Low, Hu, and Goldstein in 1981 and characterized as the principal G-actin–sequestering peptide of mammalian cells by Safer and Nachmias in 1991–1992^[1][3][4].

The published evidence base is genuinely substantial — substantially more translational than most research peptides — and includes Phase 1 intravenous safety data, Phase 2 dermal and ophthalmic efficacy data, and a completed Phase 3 trial in neurotrophic keratopathy. It is also true, and equally important, that no Tβ4 formulation has been FDA-approved for any indication, and that the largest Phase 3 trials narrowly missed their primary endpoints. This profile attempts to describe the molecule the way the primary literature describes it.

Nothing in this article is a recommendation. TB-500 is supplied by PepMax under the product slug tb-500 for laboratory research use only. It is not approved by FDA, EMA, MHRA, Health Canada, or any other regulator we ship to for human or veterinary therapeutic use, and it is prohibited at all times in sport under WADA category S2^[16].

At a glance

The data sheet below summarizes the molecule’s identity. Sequence and molecular formula derive from the original Low/Hu/Goldstein characterization^[1] and the Crockford 2010 review of structure and biological properties^[14].

Naming — TB-500, Tβ4, Ac-SDKP

Three terms in the surrounding literature are routinely conflated and should be kept distinct. Thymosin β4(Tβ4) is the endogenous 43-amino-acid, N-terminally acetylated peptide — the actual molecule studied in every primary paper cited below. TB-500is a research- and sports-market trade name for synthetic Tβ4 (or, occasionally and incorrectly, the N-terminal active fragment Ac-SDKP); there is no published pharmaceutical specification under the name “TB-500.” It is a non-clinical label, not a drug code. Ac-SDKPis the four-residue N-terminal cleavage product of Tβ4 (Ac–Ser–Asp–Lys–Pro), generated in vivo by meprin-α plus prolyl oligopeptidase. It has its own independent anti-fibrotic, pro-angiogenic, and hematopoietic-regulatory biology^[13][15] and is not interchangeable with full-length Tβ4.

For completeness: RGN-137 (topical dermal gel) and RGN-259 / timbetasin (ophthalmic solution) are the GMP-grade synthetic Tβ4 drug products developed by RegeneRx and licensees. References to clinical Phase 1/2/3 work below refer to these formulations.

Proposed mechanisms

Unlike most regulatory peptides, Tβ4 has a single, biochemically anchored primary mechanism: 1:1 sequestration of monomeric G-actin in the cytoplasm. Downstream cellular and tissue effects are interpreted as consequences of cytoskeletal dynamics that this sequestration controls.

G-actin sequestration

Safer, Elzinga, and Nachmias (1991) established that Tβ4 and the previously described actin-sequestering peptide “Fx” of platelets and polymorphonuclear leukocytes are indistinguishable^[3]. A follow-up paper the next year showed that Tβ4 is responsible for sequestering the majority of unpolymerized G-actin in resting human PMNs^[4]. This binding is stoichiometric (1:1) and competes with profilin and ADF/cofilin for the monomeric actin pool. In intact cells, the consequence is a controlled buffer of polymerization-competent actin: when motility, migration, or repair signals require it, the buffered pool is released for filament extension at the leading edge.

ILK / Akt and cardiac repair

Bock-Marquette and Srivastava (2004) reported in Nature that systemic Tβ4 activates integrin-linked kinase (ILK) and Akt in the myocardium, promotes cardiomyocyte migration and survival, and improves cardiac function after coronary ligation in mice^[5]. Smart, Riley, and colleagues (2007) extended the cardiac story in a second Naturepaper showing that Tβ4 reactivates adult epicardium-derived progenitor cells and stimulates neovascularization — reactivating an embryonic program in adult tissue^[6]. These two papers anchor the most-cited cardiac literature on Tβ4.

Corneal and dermal repair

Sosne and colleagues (2002) reported that topical Tβ4 accelerated corneal re-epithelialization after alkali burn in mice and suppressed local inflammatory signalling (NF-κB, IL-1β, chemokine production)^[7]. The combination of a migration-promoting effect on epithelial cells and a parallel anti-inflammatory effect is the rationale for the Phase 2 and Phase 3 ophthalmic-surface programs that followed (RGN-259 in dry eye and neurotrophic keratopathy)^[10][11].

Ac-SDKP — independent biology

The N-terminal four residues of Tβ4 — Ac-Ser–Asp–Lys–Pro — are released in vivo by meprin-α and prolyl oligopeptidase and have their own biology. Lenfant and colleagues (1989) originally characterized Ac-SDKP as an endogenous negative regulator of hematopoietic stem-cell proliferation isolated from fetal calf bone marrow^[13]. Subsequent work has documented anti-fibrotic effects on cardiac and renal tissue and pro-angiogenic activity. A practically relevant detail: Ac-SDKP is degraded by angiotensin-converting enzyme, and ACE inhibitors raise circulating Ac-SDKP roughly fivefold — part of the proposed anti-fibrotic mechanism of that drug class^[15]. None of this overlaps cleanly with full-length Tβ4 effects, and TB-500 should not be assumed to be interchangeable with Ac-SDKP at any dose.

Evidence map

The figure below summarizes the published Tβ4 evidence base by tissue or domain. Each row reflects the highest level of evidence we have been able to identify from peer-reviewed primary sources, not the volume of studies. Where evidence is limited to in vitro or animal models, that is stated explicitly.

Cardiac models

The cardiac literature is the most-cited preclinical sub-corpus. Bock-Marquette and colleagues (2004) injected Tβ4 systemically into mice subjected to coronary ligation and reported reduced scar formation and improved cardiac function, with corresponding ILK and Akt activation in the myocardium^[5]. Smart, Riley, and colleagues (2007) followed with the epicardial-progenitor result — that Tβ4 reactivates a normally quiescent adult epicardial progenitor pool that contributes to post-infarct revascularization^[6]. Subsequent work in larger animals (rat and pig MI) has been mixed, and a controlled Phase 2 trial of intravenous Tβ4 in human myocardial infarction has not been completed.

Corneal and dermal models

The Sosne corneal-injury model (alkali burn in mice) has been the workhorse system for translating Tβ4’s migration and anti-inflammatory effects toward an ocular-surface clinical program^[7]. In the dermal program, RGN-137 topical gel has been evaluated in pressure ulcers, venous stasis ulcers, and epidermolysis bullosa. Phase 2 dermal efficacy did not reach statistical significance on primary endpoints, despite positive trends and acceptable safety^[14].

Stroke and neurorestoration

Morris, Chopp, and colleagues (2010) reported that intraperitoneal Tβ4 (6 mg/kg) starting 24 h after embolic middle-cerebral-artery occlusion in rats improved functional neurological outcome at 1, 7, and 14 days, without changing infarct volume^[8]. The mechanistic interpretation is neurorestoration rather than neuroprotection — Tβ4 promotes oligodendrogenesis, axonal remodeling, and white-matter integrity in the peri-infarct region. There is no human stroke trial.

Human data

Across formulations, the Tβ4 human evidence base is among the most developed of any compound in the research-peptide channel.

• Phase 1 IV Tβ4 (RegeneRx): single doses up to 1 260 mg and multi-dose regimens of 42 mg/day × 14 days were well tolerated in healthy volunteers, with no dose-limiting toxicity and no drug-related serious adverse events^[9].
• Phase 1 recombinant Tβ4 (NL005):a separate first-in-human Phase 1 in healthy Chinese volunteers (single doses 0.05–25 µg/kg; multi-dose 0.5–5 µg/kg × 10 days) reported only mild-to-moderate adverse events and no SAEs^[12].
• Phase 2 RGN-259 dry eye: 0.1% Tβ4 ophthalmic solution showed significant improvement in signs and symptoms of severe dry eye in a Phase 2 randomized trial^[10].
• Phase 3 RGN-259 in neurotrophic keratopathy (SEER-1): complete corneal healing in 6 of 10 RGN-259 patients vs 1 of 8 placebo patients at 4 weeks (p ≈ 0.066). The primary endpoint was narrowly missed; multiple secondary endpoints favored RGN-259; no significant safety signals were reported^[11].
• Phase 3 RGN-259 in dry eye (SEER-3): the program disclosed that SEER-3 missed its primary endpoint. As of this writing, that result is reported in company disclosures and trade press rather than a peer-reviewed publication.

Research timeline

Limitations of the evidence base

The Tβ4 literature is more developed than most research peptides, and its limits are correspondingly different from compounds whose record is preclinical-only. The constraints any researcher should weigh explicitly:

• Mechanism is well-anchored only at the cytoskeletal level. G-actin sequestration is biochemically rigorous; ILK/Akt activation, anti-inflammatory effects, and progenitor mobilization are reported in distinct experimental systems and are not all co-measured in a single integrated study.
• Phase 3 outcomes have been statistically negative or borderline.The two largest controlled trials in the public record — SEER-1 in neurotrophic keratopathy and SEER-3 in dry eye — missed their primary endpoints. SEER-1 was a near-miss with multiple positive secondaries; SEER-3 was a clear miss.
• No completed human cardiac, tendon, or ligament trial exists. The most popular framings of TB-500 in sports and athletic-recovery contexts have no controlled human efficacy support. The cardiac case for Tβ4 rests on rodent-and-pig preclinical work that has not been translated through Phase 2.
• Equine literature is anecdotal. Despite the heavy off-label use of TB-500 in racing, no controlled, peer-reviewed equine clinical trial of Tβ4 in tendon, ligament, or muscle injury has been published.
• Long-term and oncologic safety in humans is uncharacterized. Phase 1 studies established acute safety across single and multi-dose regimens; no long-term dataset addresses chronic exposure, and the question of whether sustained Tβ4 exposure influences tumor microenvironment biology in humans is not settled.
• Ac-SDKP and full-length Tβ4 are not interchangeable.The active fragment has its own degradation pathway (ACE), its own pharmacology, and its own tissue distribution. Studies that cite “TB-500 effects” using free Ac-SDKP should be read as Ac-SDKP studies, not as Tβ4 studies.

Regulatory and WADA status

Tβ4 is investigational. No formulation has received FDA, EMA, MHRA, or Health Canada approval for any indication as of 2026. Beyond ordinary regulatory status, Tβ4 and its derivatives are explicitly prohibited at all times (in and out of competition) under section S2of the WADA Prohibited List, in the “Peptide Hormones, Growth Factors, Related Substances and Mimetics” category covering growth factors affecting muscle, tendon, ligament, and vascularization^[16]. Athletes subject to WADA testing should treat any TB-500 / Tβ4 supply — including products labeled as research-use-only — as a doping-positive risk regardless of intent.

Reconstitution & handling

TB-500 is supplied as a lyophilized powder. Standard practice across the peptide literature is reconstitution in bacteriostatic water (0.9% benzyl alcohol) for short-term storage in solution, or in sterile water for injectionwhen the bacteriostatic preservative is undesirable for a given research design. Once reconstituted, the peptide is stored at 2–8 °C and is generally treated as stable for several weeks; lyophilized powder is held at −20 °C or below, protected from light and moisture. Repeated freeze–thaw cycles should be avoided — aliquot if multiple thaws are anticipated.

For background on what the analytical numbers on a peptide’s certificate of analysis actually mean — HPLC purity, mass-spectrometric identity confirmation, water content — see our companion methods articles on what ≥99% purity actually means and how we verify peptide purity. For a side-by-side comparison of TB-500 and BPC-157 mechanisms, evidence bases, and the rationale for stacking them, see BPC-157 vs TB-500.

Further reading

The bibliography below points to the primary papers and reviews referenced in this profile. Crockford et al. 2010^[14] and Xing et al. 2021^[15] are useful entry-point reviews; the Bock-Marquette^[5] and Smart^[6] Nature papers anchor the cardiac literature; Sosne 2023 is the Phase 3 ophthalmic readout^[11].