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Safe TB-500

Reading list

TB-500 and thymosin beta-4 references

Studies and regulatory documents on TB-500, thymosin beta-4 and the safety questions surrounding them.

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Structural, clinical and safety documents

For chemical identity, start with Ho and colleagues’ equine detection study and Irobi and colleagues’ actin-binding structure. They examine different preparations and answer different questions. For human exposure, the Ruff Phase 1 study and the withdrawn heart-attack trial record are the key documents here.

The dystrophin-deficient mouse experiment is the functional test that best exposes the weakness of equating regeneration with restored function. For safety, the tumor metastasis and angiogenesis paper and the 2026 sports-medicine review supply different kinds of concern. The FDA entries record nomination and compounding status; the meeting notice records a planned discussion. The reading list brings these studies, trial records and regulatory documents together.

  1. Irobi E, Aguda AH, Larsson M, et al. Structural basis of actin sequestration by thymosin-beta4: implications for WH2 proteins. EMBO J. 2004;23(18):3599-3608. ↗
  2. Malinda KM, Sidhu GS, Mani H, et al. Thymosin beta4 accelerates wound healing. J Invest Dermatol. 1999;113(3):364-368. ↗
  3. Bock-Marquette I, Saxena A, White MD, et al. Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature. 2004;432(7016):466-472. ↗
  4. Ruff D, Crockford D, Girardi G, Zhang Y. A randomized, placebo-controlled, single and multiple dose study of intravenous thymosin beta4 in healthy volunteers. Ann N Y Acad Sci. 2010;1194:223-229. ↗
  5. Goldstein AL, Hannappel E, Sosne G, Kleinman HK. Thymosin beta4: a multi-functional regenerative peptide. Basic properties and clinical applications. Expert Opin Biol Ther. 2012;12(1):37-51. ↗
  6. Tokura Y, Nakayama Y, Fukada S, et al. Muscle injury-induced thymosin beta4 acts as a chemoattractant for myoblasts. J Biochem. 2011;149(1):43-48. ↗
  7. Xu B, et al. Thymosin beta4 enhances the healing of medial collateral ligament injury in rats. Regul Pept. 2013;184:1-8. ↗
  8. Morris DC, Chopp M, Zhang L, Zhang ZG. A dose-response study of thymosin beta4 for the treatment of acute stroke. J Neurol Sci. 2014;345(1-2):61-67. ↗
  9. Spurney CF, Cha HJ, Sali A, et al. Evaluation of skeletal and cardiac muscle function after chronic administration of thymosin beta-4 in the dystrophin deficient mouse. PLoS One. 2010;5(1):e8976. ↗
  10. Kleinman HK, Sosne G. Thymosin beta4 promotes dermal healing. Animal studies with thymosin beta, a multifunctional tissue repair and regeneration peptide (including porcine ischemia-reperfusion data). Ann N Y Acad Sci. 2010;1194:118-122. ↗
  11. RegeneRx Biopharmaceuticals (sponsor). A Study of the Safety and Efficacy of Injectable Thymosin Beta 4 for Treating Acute Myocardial Infarction (withdrawn). ClinicalTrials.gov identifier NCT01311518. 2011. ↗
  12. Jo JO, Kang YJ, Ock MS, et al. Thymosin beta4 induces the expression of vascular endothelial growth factor (VEGF) in a hypoxia-inducible factor (HIF)-1alpha-dependent manner. Biochim Biophys Acta. 2010;1803(11):1244-1251. ↗
  13. Kleinman HK, Sosne G, Goldstein AL. Thymosin beta4 and cancer: pro-migratory and pro-angiogenic properties implicated in tumor progression and metastasis (review of the oncologic safety signal). Expert Opin Biol Ther. 2012;12(Suppl 1). ↗
  14. Qiu P, Wheater MK, Qiu Y, Sosne G. Thymosin beta4 promotes matrix metalloproteinase expression during wound repair. J Cell Physiol. 2006;209(2):611-617. ↗
  15. Mendias CL, Awan TM. Safety and Efficacy of Approved and Unapproved Peptide Therapies for Musculoskeletal Injuries and Athletic Performance. Sports Med. 2026. ↗
  16. Gonzalez-Franquesa A, Stocks B, Borg ML, et al. Discovery of thymosin beta4 as a human exerkine and growth factor. Am J Physiol Cell Physiol. 2021;321(5):C770-C778. ↗
  17. U.S. Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding That May Present Significant Safety Risks (list entry: 'Thymosin beta-4, fragment (LKKTETQ), also known as TB-500'; nomination withdrawn; FDA safety concerns remain). ↗
  18. U.S. Food and Drug Administration. Bulk Drug Substances Used in Compounding Under Section 503A of the FD&C Act (Category 1 and Category 2 definitions; 503A/503B framework; nomination and PCAC process). ↗
  19. U.S. Food and Drug Administration. July 23-24, 2026: Meeting of the Pharmacy Compounding Advisory Committee (agenda lists 'TB-500 (free base)' / 'TB-500 acetate', BPC-157, KPV, and MOTs-C as substances being considered for inclusion on the 503A Bulks List; a scheduled discussion, not a decision). ↗
  20. Cha HJ, Jeong MJ, Kleinman HK. Role of thymosin beta4 in tumor metastasis and angiogenesis. J Natl Cancer Inst. 2003. ↗
  21. Zhang Y, et al. Thymosin beta 4 is overexpressed in human pancreatic cancer cells and stimulates proinflammatory cytokine secretion and JNK activation. Cancer Biol Ther. 2008. ↗
  22. Ho EN, et al. Doping control analysis of TB-500, a synthetic version of an active region of thymosin β4, in equine urine and plasma by liquid chromatography-mass spectrometry. J Chromatogr A. 2012. ↗
  23. Delcourt V, et al. TB500/TB1000 and SGF1000: A scientific approach for a better understanding of misbranded and adulterated drugs. Drug Test Anal. 2023. ↗