Peptide Briefs

TB-500

Evidence grade: C — reviewed September 2026

Published controlled human trials of TB-500: 0 · Controlled human trials of full-length thymosin β4: 5+ · Animal studies (fragment): ~10 · Animal studies (full Tβ4): 100+

Also known as: Thymosin β4 fragment 17–23, Ac-LKKTETQ, “TB4” (loosely)

Sequence: Ac-Leu-Lys-Lys-Thr-Glu-Thr-Gln (7 amino acids, N-terminally acetylated)

Related entry: Thymosin β4 (full-length, 43 amino acids) — grade B

TB-500 is the most misattributed compound in the research-peptide market. It is a synthetic seven-amino-acid piece of thymosin β4, a 43-amino-acid protein present in nearly every human cell. The full protein has been tested in randomized, placebo-controlled human trials — for dry eye, for a rare corneal disease, for heart attack, for leg ulcers. The seven-amino-acid fragment sold as TB-500 has not. When a vendor cites “human clinical evidence for TB-500,” they are almost always quoting a thymosin β4 study and hoping you won’t notice the difference. Peptide Briefs grades the fragment C on its own record and lists the full-protein evidence separately so the distinction stays visible.

What TB-500 is

Thymosin β4 (Tβ4) binds G-actin, the building block of the cell’s internal scaffolding, and in doing so influences how cells move, migrate, and organize during repair. In the early 2000s, researchers identified the short segment of Tβ4 responsible for actin binding — residues 17 through 23, LKKTETQ — and showed that this fragment alone reproduced some of the parent protein’s effects on cell migration in laboratory models. TB-500 is that fragment, chemically capped at one end for stability.

The full protein was developed for human use by RegeneRx Biopharmaceuticals (and its partner ReGenTree) under the code RGN-259 for eye conditions and RGN-352 as an injectable. The fragment was never developed as a drug by anyone.

What the studies looked at

The fragment (TB-500 proper).

  • Philp et al. (2003) showed that the actin-binding fragment accelerated wound closure in diabetic and aged mice, the key result behind the compound’s reputation. Mice, not people.
  • A handful of subsequent in-vitro and rodent papers examined the fragment’s effects on cell migration and angiogenesis, mostly confirming the actin-binding mechanism.
  • A 2026 scoping review of Tβ4 and TB-500 in musculoskeletal repair found the fragment-specific literature thin and dominated by preclinical work.

Full-length thymosin β4 (RGN-259 / RGN-352) — human trials.

  • Dry eye, Phase 2 (2015): 72 subjects randomized to 0.1% Tβ4 eye drops or placebo for 28 days in a controlled adverse environment; improvements in corneal staining, with mixed symptom results.
  • Severe dry eye, Phase 2 (2015): nine patients; statistically significant reductions in ocular discomfort and corneal staining versus vehicle.
  • Neurotrophic keratopathy, Phase 3 (SEER-1, 2022): randomized, placebo-controlled, double-masked; RGN-259 promoted healing of persistent corneal epithelial defects.
  • Dry eye, Phase 3 (ARISE-1, -2, -3; ~1,600 patients combined): three placebo-controlled trials between 2016 and 2021. The FDA required ARISE-3 after the first two did not demonstrate efficacy in both signs and symptoms; the sponsor reported favorable results in pooled analyses, but no approval application has followed.
  • Acute myocardial infarction (RGN-352, NCT01311518): Phase 2 safety study of injectable Tβ4; enrollment was halted for manufacturing reasons, and efficacy was not established.
  • Venous stasis ulcers, Phase 2 (NCT00832091): topical Tβ4; results reported as safe with modest healing signals.
  • Cardiac pilot (Zhu et al., 2016): small intravenous Tβ4 study.

Animal and in-vitro work on full Tβ4: extensive — cardiac repair after infarction, corneal healing, skin wound closure, hair growth, spinal cord injury. This is the literature most often quoted in TB-500 marketing.

What the evidence does not show

  • No published human trial of the seven-amino-acid fragment for any indication, by any route.
  • No published human data on injectable TB-500 or Tβ4 for tendon, ligament, or muscle recovery — the uses the compound is best known for online.
  • No evidence that the fragment and the full protein are interchangeable in humans; they have not been compared head-to-head.
  • The strongest human results for full Tβ4 are topical eye-drop trials in eye disease, which say nothing about systemic use.
  • Three Phase 3 dry-eye trials of full Tβ4 have not produced an approval — a reminder that small positive trials do not reliably replicate at scale.

Regulatory and sport status

  • FDA (US): Neither TB-500 nor Tβ4 is approved for any use. RGN-259 has orphan-drug and fast-track designations for neurotrophic keratopathy but is not marketed.
  • WADA: Thymosin β4 and its fragments are prohibited in sport under section S2 (peptide hormones, growth factors, and mimetics).
  • Legal supply: Sold in the US only as a research-use-only chemical. Note that some vendors sell full-length Tβ4 under the TB-500 name and vice versa; a certificate of analysis with mass-spec identity is the only way to know which you have. The expected mass for Ac-LKKTETQ is about 889 Da; for full Tβ4 about 4,963 Da.

Stability, storage, and handling in the laboratory

Lyophilized TB-500 is stable at −20 °C for extended periods and tolerates brief room-temperature exposure in shipping. Reconstituted in bacteriostatic water, laboratory practice is 2–8 °C and use within a few weeks. The N-terminal acetyl group improves stability relative to the unmodified fragment, but repeated freeze–thaw cycles and warmth still degrade it. Identity by mass spectrometry matters more for this compound than for most, because the fragment and full protein are routinely confused on labels.

Common questions

Is TB-500 the same as thymosin β4? No. TB-500 is a 7-amino-acid piece of the 43-amino-acid protein. The human trials are on the full protein.

Then why is TB-500 sold instead of Tβ4? The fragment is far cheaper to synthesize, and early mouse work suggested it carried the actin-binding activity. Whether it carries the full protein’s effects in humans has never been tested.

Does TB-500 heal tendons and muscle? In mice and in cell culture, the fragment promotes cell migration. In humans, that question has not been asked in a published study.

Why does Peptide Briefs grade it C when there are human trials? Because the trials are on a different molecule. The Briefs grade a compound on its own record. Full-length Tβ4 gets a B on its own page, with the note that its strongest evidence is topical and ophthalmic.

Could the grade change? A published controlled human trial of the fragment itself would move it to B, whatever the result.

Sources

  1. Philp D, Badamchian M, Scheremeta B, Nguyen M, Goldstein AL, Kleinman HK. Thymosin β4 and a synthetic peptide containing its actin-binding domain promote dermal wound repair in db/db diabetic mice and in aged mice. Wound Repair Regen. 2003;11(1):19–24. PMID 12581423.
  2. Philp D, Huff T, Gho YS, Hannappel E, Kleinman HK. The actin binding site on thymosin β4 promotes angiogenesis. FASEB J. 2003;17(14):2103–2105.
  3. Goldstein AL, Hannappel E, Sosne G, Kleinman HK. Thymosin β4: a multi-functional regenerative peptide. Basic properties and clinical applications. Expert Opin Biol Ther. 2012;12(1):37–51. PMID 22074294.
  4. Sosne G, Ousler GW. Thymosin beta 4 ophthalmic solution for dry eye: a randomized, placebo-controlled, Phase II clinical trial conducted using the controlled adverse environment (CAE) model. Clin Ophthalmol. 2015;9:877–884. PMID 26056426.
  5. Sosne G, Dunn SP, Kim C. Thymosin β4 significantly improves signs and symptoms of severe dry eye in a phase 2 randomized trial. Cornea. 2015;34(5):491–496. PMID 25826322.
  6. Sosne G, et al. 0.1% RGN-259 (thymosin β4) ophthalmic solution promotes healing and improves comfort in neurotrophic keratopathy patients in a randomized, placebo-controlled, double-masked phase III clinical trial. Int J Mol Sci. 2022.
  7. Zhu J, et al. Thymosin β4 in cardiac repair (intravenous pilot). Cytotherapy. 2016. PMID 27288307.
  8. RegeneRx Biopharmaceuticals. RGN-352 in acute myocardial infarction. ClinicalTrials.gov NCT01311518.
  9. RegeneRx Biopharmaceuticals. Thymosin β4 in venous stasis ulcers. ClinicalTrials.gov NCT00832091.
  10. ReGenTree LLC. ARISE-2: RGN-259 in dry eye syndrome. ClinicalTrials.gov NCT02974907; ARISE-1 and ARISE-3 registered separately (Phase 3 program, 2016–2021).
  11. Thymosin Beta-4 and TB-500 in Tissue Healing, Regeneration, and Musculoskeletal Repair: A Scoping Review. Appl Sci. 2026;16(12):6202.
  12. Nguyen MT, et al. Thymosin β4 in tissue repair (review). Cells. 2023;12(21):2523.
  13. WADA Prohibited List 2026, section S2.

Peptide Briefs is an independent reference published by the founders of Agape Compounds LLC. Nothing on this page is medical advice or a recommendation to use any compound outside a research setting. Grade reviewed September 2026.