Thymosin Beta-4 (Tβ4)

It is like a new car that passed its safety tests but kept missing its fuel-economy targets on the official test track. It is safe enough to keep testing, but not yet good enough to sell. Meanwhile people are buying unbadged versions to race off-road, a use nobody has tested at all.

Thymosin beta-4 binds single actin molecules (G-actin) and holds them in reserve, controlling how quickly cells can build the actin filaments they need to change shape and move. Through this, and through signalling effects that are less well mapped, it encourages cells to migrate into wounds, supports new blood-vessel growth, dampens inflammation and scarring, and helps damaged cells survive. TB-500 copies only the short actin-binding stretch (positions 17-23); the full molecule has other active regions, such as the N-terminal Ac-SDKP piece, which is one reason results for one cannot be assumed for the other. In trials it was given as eye drops, a skin gel and by intravenous infusion.

Research contexts. Not proven uses, and not recommendations.

Real but underwhelming. Full-length thymosin beta-4 has been given to well over a thousand people across Phase 1 to Phase 3 trials, mostly as eye drops for dry eye (three Phase 3 ARISE trials enrolling 317, 601 and 700 people) and neurotrophic keratopathy, and in smaller trials as a wound gel and an intravenous heart drug. Safety has been consistently good, with mostly mild side effects. Efficacy has not: ARISE-3 missed its primary outcomes, SEER-1 fell just short of significance in 18 patients, the European SEER-3 trial missed its primary goal in 2025, and a 96-patient Chinese heart attack trial found no overall difference in infarct size. Phase 2 ulcer trials suggested faster healing in some patients but were small. Most trials were run or funded by the companies developing it. No approval has resulted. There are no human trials of thymosin beta-4 injected for sports injuries, tendons, muscle or recovery, which is how it is used on the grey market.

• !Efficacy in people is unproven: several late-stage trials missed their primary goals and no product has been approved.
• !The trials used eye drops, a skin gel or supervised IV doses for specific diseases; none tested self-injection for sports injuries or recovery.
• !Theoretical cancer concern: a peptide that promotes cell migration and new blood-vessel growth could in principle aid tumour growth; higher TMSB4X expression was associated with worse survival in a lung cancer study. This is not proven to apply to people taking it.
• !Not licensed anywhere; grey-market products are sold as 'research chemicals, not for human consumption', and a 2023 lab analysis found products sold as TB500/TB1000 did not consistently contain what they claimed.
• !Sellers often blur thymosin beta-4 and TB-500; the label may not tell you which molecule is in the vial.
• !Banned at all times in sport by WADA (S2.3).

Not a licensed medicine in the UK. The MHRA has authorised no thymosin beta-4 product, and no thymosin beta-4 product (including RGN-259) has marketing authorisation anywhere. It is not a controlled drug under the Misuse of Drugs Act 1971 (the Class C hormone list covers somatropin and related growth hormones, not thymosin beta-4). It is sold online as an unlicensed 'research chemical, not for human consumption'; supplying or marketing it for human use would breach the Human Medicines Regulations 2012. Outside a clinical trial there is no lawful route to obtain it as a medicine in the UK.

• NCT03937882· Phase 3· Completed (700 enrolled); did not meet primary outcome measures (2021)

  Assessment of the Safety and Efficacy of RGN-259 Ophthalmic Solutions for Dry Eye Syndrome: ARISE-3

  Largest thymosin beta-4 trial. Eye drops, not injection.

• NCT02600429· Phase 3· Terminated (18 enrolled); results published 2022

  Assessment of the Safety and Efficacy Study of RGN-259 Ophthalmic Solutions for Neurotrophic Keratopathy: SEER-1

  Complete healing 6/10 vs 1/8 at 4 weeks, p=0.0656.

• NCT05555589· Phase 3· Recruiting (started 2023)

  Assessment of the Safety and Efficacy of 0.1% RGN-259 Ophthalmic Solution for the Treatment of NK: SEER-2

  US trial; the remaining late-stage test of RGN-259.

• NCT00832091· Phase 2· Completed

  Study of Thymosin Beta 4 in Patients With Venous Stasis Ulcers

  Topical gel (RGN-137); published by Guarnera et al. 2010.

• NCT05984134· Phase 2· Completed (90 enrolled); no results posted

  Efficacy and Safety Study of Thymosin Beta 4 in Patients With Acute Myocardial Infarction

  Recombinant NL005 by IV, China. A related 96-patient trial was published in Cardiovascular Research (2025) with no overall difference in infarct size.

1. 01
   0.1% RGN-259 (Thymosin ß4) Ophthalmic Solution Promotes Healing and Improves Comfort in Neurotrophic Keratopathy Patients in a Randomized, Placebo-Controlled, Double-Masked Phase III Clinical Trial — Sosne G, Kleinman HK, Springs C, Gross RH, Sung J, Kang S, International Journal of Molecular Sciences (2022)

   SEER-1: 18 patients; complete healing at 4 weeks 6/10 vs 1/8 (p=0.0656, not significant); some later and secondary measures significant. Authors include sponsor employees.

2. 02
   RegeneRx Reports Topline Results of ARISE-3 Dry Eye Trial, RegeneRx Biopharmaceuticals press release (2021)

   ARISE-3 Phase 3 'did not meet its primary outcome measures'; no serious adverse events; mild eye discomfort most frequent ophthalmic side effect.

3. 03
   HLB Therapeutics misses primary end point in phase 3 SEER-3 trial of RGN-259, Ophthalmology Times (2025)

   European Phase 3 in neurotrophic keratitis did not show a significant difference in complete corneal healing at 4 weeks; SEER-2 in the US continues.

4. 04
   Recombinant human thymosin beta 4 improves ischemic cardiac dysfunction in mice and patients with acute ST-segment elevation myocardial infarction after reperfusion — Zhang Y, Dong Q, Bian X, et al., Cardiovascular Research (2025)

   Randomised placebo-controlled trial in 96 STEMI patients: no significant overall difference in infarct area; smaller infarcts in the subgroup dosed within 8 h. Some authors employed by the manufacturer.

5. 05
   A randomized, placebo-controlled, single and multiple dose study of intravenous thymosin beta4 in healthy volunteers — Ruff D, Crockford D, Girardi G, Zhang Y, Annals of the New York Academy of Sciences (2010)

   Phase 1 IV safety study, four cohorts of 10; adverse events infrequent and mild to moderate.

6. 06
   The effect of thymosin treatment of venous ulcers — Guarnera G, DeRosa A, Camerini R, Annals of the New York Academy of Sciences (2010)

   Phase 2 topical gel trial, 73 randomised; safety comparable to placebo; suggestion of faster healing at one dose.

7. 07
   Thymosin beta 4 ophthalmic solution for dry eye: a randomized, placebo-controlled, Phase II clinical trial conducted using the controlled adverse environment (CAE) model — Sosne G, Ousler GW, Clinical Ophthalmology (2015)

   72 patients; neither primary endpoint met; some secondary endpoints significant.

8. 08
   A first-in-human, randomized, double-blind, single- and multiple-dose, phase I study of recombinant human thymosin β4 in healthy Chinese volunteers — Wang X, Liu L, Qi L, et al., Journal of Cellular and Molecular Medicine (2021)

   NL005 Phase 1: mild to moderate adverse events, no dose-limiting toxicity or serious adverse events.

9. 09
   TB500/TB1000 and SGF1000: A scientific approach for a better understanding of misbranded and adulterated drugs — Delcourt V, Garcia P, Chabot B, et al., Drug Testing and Analysis (2023)

   Analysis of internet products: TB500/TB1000 content not consistently matching descriptions.

10. 10
    TMSB4X: A novel prognostic marker for non-small cell lung cancer — Yang Z, Luo J, Zhang M, et al., Heliyon (2023)

    Higher TMSB4X expression associated with worse survival in lung cancer. Correlation only.

11. 11
    Thymosin beta-4 (TMSB4X), human: UniProtKB P62328, UniProt

    Sequence (43 residues after initiator methionine removal), N-acetylserine, actin-monomer sequestering function, AcSDKP hemoregulatory peptide.

12. 12
    World Anti-Doping Code International Standard: Prohibited List 2026 (official reproduction, Austrian Federal Law Gazette BGBl. III Nr. 219/2025), World Anti-Doping Agency (2025)

    S2.3 names 'Thymosin-β4 and its derivatives e.g. TB-500'. Gazette reproduction of the WADA list; the wada-ama.org page is https://www.wada-ama.org/en/prohibited-list.