# TB-500 References — Customs manifest of the cited research and regulatory record

> Full citation list for the TB-500 Legal research record: 24 entries spanning Thymosin Beta-4 mechanism, preclinical studies, clinical trials, and regulatory actions, with DOIs and primary-source URLs.

The full reference list — twenty-four entries from in vitro biochemistry to regulatory enforcement.

## About this manifest

Every claim made on this site is sourced to one or more of the entries below. The manifest spans the foundational biochemistry of Thymosin Beta-4 — actin sequestration, HIF-1α and VEGF, NF-κB inhibition, PINCH–ILK–Akt cardiac signaling, AcSDKP antifibrotic activity — through the preclinical record in mouse, rat, pig, and equine models, into the Phase I and Phase II/III clinical-development programs for the full-length recombinant peptide. It includes the regulatory enforcement record (FDA 503A Category 2 placement; WADA 2025 Prohibited List entries; USADA athlete sanction) and the validated equine doping-control detection method.

Where multiple citations bear on a single topic, the most-cited or most-recent primary source is given preference. Where a regulatory finding is the citation, the original agency document is linked directly. DOIs are provided where available; PubMed, PMC, and ClinicalTrials.gov URLs are provided for primary research; agency URLs are provided for regulatory entries.

The table is sortable, searchable, and filterable by year, species, journal, and authority. The customs-manifest treatment is intentional: a single document of record.

## The citation list

The full reference list appears below, organized as a single sortable manifest. Each entry includes the citation, DOI or identifier, and a direct URL to the primary source.

## References

[1] Jo JO, Kim SR, Bae MK, Kang YJ, Ock MS, Kleinman HK, Cha HJ. Thymosin β4 induces the expression of vascular endothelial growth factor (VEGF) in a hypoxia-inducible factor (HIF)-1α-dependent manner. Biochim Biophys Acta Mol Cell Res. 2010. https://pubmed.ncbi.nlm.nih.gov/20691219/
[2] Ryu YK, Kang JH, Moon EY. The Actin-Sequestering Protein Thymosin Beta-4 Is a Novel Target of Hypoxia-Inducible Nitric Oxide and HIF-1α Regulation. PLoS One. 2014. https://pmc.ncbi.nlm.nih.gov/articles/PMC4182666/
[3] Kim S, Kwon J. Thymosin beta4 induces angiogenesis through Notch signalling in endothelial cells. Cell Signal. 2013. https://pubmed.ncbi.nlm.nih.gov/23749167/
[4] Qiu P, Wheater MK, Qiu Y, Sosne G. Thymosin β4 inhibits TNF-α-induced NF-κB activation, IL-8 expression, and the sensitizing effects of its partners PINCH-1 and ILK. FASEB J. 2011. https://pmc.ncbi.nlm.nih.gov/articles/PMC3101037/
[5] Yang HM, Kang SW, Sung J, Kim K, Kleinman HK. Purinergic Signaling Involvement in Thymosin β4-mediated Corneal Epithelial Cell Migration. Curr Eye Res. 2020. https://pubmed.ncbi.nlm.nih.gov/32223337/
[6] Sosne G, Szliter EA, Barrett R, Kernacki KA, Kleinman H, Hazlett LD. Thymosin beta 4 promotes corneal wound healing and decreases inflammation in vivo following alkali injury. Exp Eye Res. 2002. https://pubmed.ncbi.nlm.nih.gov/11950239/
[7] Xiong Y, Zhang Y, Mahmood A, Meng Y, Zhang ZG, Morris DC, Chopp M. Neuroprotective and neurorestorative effects of thymosin beta4 treatment initiated 6 hours post injury following traumatic brain injury in rats. J Neurosurg. 2012. https://pmc.ncbi.nlm.nih.gov/articles/PMC3392183/
[8] Morris DC, Chopp M, Zhang L, Lu M, Zhang ZG. Thymosin β4 improves functional neurological outcome in a rat model of embolic stroke. Neuroscience. 2010. https://pmc.ncbi.nlm.nih.gov/articles/PMC2907184/
[9] Smart N, Risebro CA, Melville AAD, Moses K, Schwartz RJ, Chien KR, Riley PR. Thymosin β4 induces adult epicardial progenitor mobilization and neovascularization. Nature. 2007. https://pubmed.ncbi.nlm.nih.gov/17108969/
[10] Bock-Marquette I, Saxena A, White MD, DiMaio JM, Srivastava D. Thymosin β4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature. 2004. https://pubmed.ncbi.nlm.nih.gov/15565145/
[11] Wei C, Kumar S, Kim IK, Gupta S. Systemic dosing of thymosin beta 4 before and after ischemia does not attenuate global myocardial ischemia-reperfusion injury in pigs. Front Pharmacol. 2016. https://pmc.ncbi.nlm.nih.gov/articles/PMC4853610/
[12] 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. https://pubmed.ncbi.nlm.nih.gov/20536472/
[13] Beijing Northland Biotech. Efficacy and Safety Study of Thymosin Beta 4 in Patients With Acute Myocardial Infarction. ClinicalTrials.gov NCT05984134. 2023. https://clinicaltrials.gov/study/NCT05984134
[14] Sosne G, Kleinman HK, Springs C, Gross RH, Sung J, Kang S. 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. https://pmc.ncbi.nlm.nih.gov/articles/PMC9820614/
[15] Esposito S, Deventer K, Goeyens L, Van Eenoo P. 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. Anal Chim Acta. 2012. https://www.sciencedirect.com/science/article/abs/pii/S0021967312014550
[16] Sosne G, Kleinman HK, et al. Engineered Tandem Thymosin Peptide Promotes Corneal Wound Healing. Int J Mol Sci. 2024. https://pmc.ncbi.nlm.nih.gov/articles/PMC12636994/
[17] Yu H, Wang B, Li Z, et al. Tβ4-exosome-loaded hemostatic and antibacterial hydrogel to improve vascular regeneration and modulate macrophage polarization for diabetic wound treatment. Mater Today Bio. 2025. https://pmc.ncbi.nlm.nih.gov/articles/PMC11893380/
[18] Lee S, Lee H, Bae S, Kim E, Oh GT, Park H, Yeon JE, Byun KS, Kim K. Targeted deletion of thymosin beta 4 in hepatic stellate cells ameliorates liver fibrosis in a transgenic mouse model. Cells. 2023. https://pmc.ncbi.nlm.nih.gov/articles/PMC10297343/
[19] Conte E, Genovese T, Gili E, Esposito E, Iemmolo M, Fruciano M, Fagone E, Pistorio MP, Crimi N, Cuzzocrea S, Vancheri C. Tβ4–Ac-SDKP pathway: Any relevance for the cardiovascular system? Can J Physiol Pharmacol. 2019. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824425/
[20] U.S. Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. 21 CFR Part 216. 2023. https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks
[21] World Anti-Doping Agency. The World Anti-Doping Code International Standard — Prohibited List 2025. WADA, 2024. https://www.wada-ama.org/sites/default/files/2024-09/2025list_en_final_clean_12_september_2024.pdf
[22] Irobi E, Aguda AH, Larsson M, Guerin C, Yin HL, Burtnick LD, Blanchoin L, Robinson RC. Structural basis of actin sequestration by thymosin-β4: implications for WH2 proteins. EMBO J. 2004. https://pmc.ncbi.nlm.nih.gov/articles/PMC517612/
[23] Wang X, Liu L, Qi L, Lei C, Li P, Wang Y, Liu C, Bai H, Han C, Sun Y, Liu J. A first-in-human, randomized, double-blind, single- and multiple-dose, phase I study of recombinant human thymosin β4 in healthy Chinese volunteers. J Cell Mol Med. 2021. https://pmc.ncbi.nlm.nih.gov/articles/PMC8419156/
[24] Xing Y, Ye Y, Zuo H, Li Y. Progress on the function and application of thymosin β4. Front Endocrinol. 2021. https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.767785/full
[25] U.S. Anti-Doping Agency. Michael Nackoul Accepts Doping Sanction. USADA Sanction Notice, 2018. https://www.usada.org/sanction/michael-nackoul-accepts-doping-sanction/
[26] Mendias CL, Awan TM. Safety and Efficacy of Approved and Unapproved Peptide Therapies for Musculoskeletal Injuries and Athletic Performance. Sports Med. 2026. https://pubmed.ncbi.nlm.nih.gov/41966639/
[27] Cha HJ, Jeong MJ, Kleinman HK. Role of thymosin beta4 in tumor metastasis and angiogenesis. J Natl Cancer Inst. 2003. https://pubmed.ncbi.nlm.nih.gov/14625258/
[28] Wang WS, et al. Thymosin beta 4 is overexpressed in human pancreatic cancer cells and stimulates proinflammatory cytokine secretion and JNK activation. Cancer Biol Ther. 2008. https://pubmed.ncbi.nlm.nih.gov/18094619/
[29] Cooper TM, 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. https://pubmed.ncbi.nlm.nih.gov/23084823/
[30] Spurney CF, et al. Evaluation of skeletal and cardiac muscle function after chronic administration of thymosin beta-4 in the dystrophin deficient mouse. PLoS One. 2010. https://pubmed.ncbi.nlm.nih.gov/20126456/
[31] 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. https://pubmed.ncbi.nlm.nih.gov/22074294/
[32] Thomas A, et al. TB500/TB1000 and SGF1000: A scientific approach for a better understanding of doping-relevant peptide preparations. Drug Test Anal. 2023. https://pubmed.ncbi.nlm.nih.gov/36482504/

---

An independent editorial survey of the published regulatory and research record — not a clinic, not a vendor, not legal counsel.