# References — TB-500 and Thymosin Beta-4 peer-reviewed sources

> Full citation list for the TB-500 and Thymosin Beta-4 research summarised on this site. Sortable, searchable, with DOIs and PubMed/PMC URLs.

Every claim on this site attaches to a citation below. Sort by year, filter by species, or search by author. All identifiers link to PubMed, PMC, or the publishing journal.

## Citation console

The table below renders the full reference set. Sort by year for chronological reading from Cassimeris 1992 to Yu 2025. Filter by species to separate human Phase I/II/III work from rodent, porcine, and equine preclinical studies. Search by author for the named lineages (Sosne and Kleinman on corneal repair; Bock-Marquette, Smart, and Riley on cardiac repair; Morris and Chopp on stroke; Ruff and Wang on human Phase I safety).

Identifiers are rendered in monospace: DOIs in the format `10.xxxx/...`, NCT identifiers in the format `NCT02600429`, CAS in the format `885340-08-9`. Where a PMC or PubMed URL is available, the citation row is linked directly to the open-access record.

## Citation key

Cyan rows indicate human clinical-trial sources — Phase I safety in healthy volunteers, Phase II/III ophthalmic and cardiac programmes, and the published clinical-biomarker record. Lime rows indicate preclinical and in-vitro sources — rodent and porcine models, equine pharmacokinetics, and biochemical structural work. Orange rows indicate regulatory and review sources — the modern Tβ4 reviews and the disambiguation literature.

The categorical legend matches the site colour vocabulary. No reference is categorised by colour alone — the journal, year, and species columns in the console table carry the same information independently.

## References

[1] Cassimeris L, Safer D, Nachmias VT, Zigmond SH. Interaction of thymosin beta 4 with muscle and platelet actin: implications for actin sequestration in resting platelets. Biochemistry. 1992;31(35):8290-8298. https://pubmed.ncbi.nlm.nih.gov/1627561/
[2] 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 Journal. 2004;23(18):3599-3608. https://pmc.ncbi.nlm.nih.gov/articles/PMC517612/
[3] Malinda KM, Sidhu GS, Mani H, Banaudha K, Maheshwari RK, Goldstein AL, Kleinman HK. Thymosin β4 accelerates wound healing. Journal of Investigative Dermatology. 1999;113(3):364-368. https://www.jidonline.org/article/S0022-202X(15)40595-0/fulltext
[4] 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. Experimental Eye Research. 2002;74(2):293-299. https://pubmed.ncbi.nlm.nih.gov/11950239/
[5] 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 and Regeneration. 2003;11(1):19-24. https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1524-475X.2003.11105.x
[6] 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;432(7016):466-472. https://pubmed.ncbi.nlm.nih.gov/15565145/
[7] 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;445(7124):177-182. https://pubmed.ncbi.nlm.nih.gov/17108969/
[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;169(2):674-682. https://pmc.ncbi.nlm.nih.gov/articles/PMC2907184/
[9] Morris DC, Cui Y, Cheung WL, Lu M, Zhang L, Zhang ZG, Chopp M. A dose-response study of thymosin β4 for the treatment of acute stroke. Journal of the Neurological Sciences. 2014;345(1-2):61-67. https://pmc.ncbi.nlm.nih.gov/articles/PMC4177939/
[10] 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 Journal. 2011;25(6):1815-1826. https://pmc.ncbi.nlm.nih.gov/articles/PMC3101037/
[11] Philp D, Nguyen M, Scheremeta B, St-Surin S, Villa AM, Orgel A, Kleinman HK, Elkin M. Thymosin β4 increases hair growth by activation of hair follicle stem cells. FASEB Journal. 2004;18(2):385-387. https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.03-0244fje
[12] Tokura Y, Nakayama Y, Fukada S, Nara N, Yamamoto H, Matsuda R, Hara T. Muscle injury-induced thymosin β4 acts as a chemoattractant for myoblasts. Journal of Biochemistry. 2011;149(1):43-48. https://pubmed.ncbi.nlm.nih.gov/20880960/
[13] Ruff D, Crockford D, Girardi G, Zhang Y. A randomized, placebo-controlled, single and multiple dose study of intravenous thymosin beta4 in healthy volunteers. Annals of the New York Academy of Sciences. 2010;1194:223-229. https://pubmed.ncbi.nlm.nih.gov/20536472/
[14] 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. Journal of Cellular and Molecular Medicine. 2021;25(16):7841-7852. https://pmc.ncbi.nlm.nih.gov/articles/PMC8419156/
[15] 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. International Journal of Molecular Sciences. 2022;24(1):554. https://pmc.ncbi.nlm.nih.gov/articles/PMC9820614/
[16] 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. Analytica Chimica Acta. 2012;752:99-104. https://www.sciencedirect.com/science/article/abs/pii/S0021967312014550
[17] 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. Frontiers in Pharmacology. 2016;7:115. https://pmc.ncbi.nlm.nih.gov/articles/PMC4853610/
[18] Romanic AM, Krais T, Lehmann K, et al. Thymosin β4 and its cleavage product Ac-SDKP are down-regulated in left ventricular myocardium of patients with advanced heart failure. Journal of Heart and Lung Transplantation. 2015;34(10):S138. https://www.jhltonline.org/article/S1053-2498(15)00265-X/fulltext
[19] 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;12(12):1658. https://pmc.ncbi.nlm.nih.gov/articles/PMC10297343/
[20] 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. Materials Today Bio. 2025;30:101585. https://pmc.ncbi.nlm.nih.gov/articles/PMC11893380/
[21] Yang J, Sosne G, Kleinman HK, Springs C, Bhamidipati A, et al. Engineered Tandem Thymosin Peptide Promotes Corneal Wound Healing. International Journal of Molecular Sciences. 2024;25(19):10347. https://pmc.ncbi.nlm.nih.gov/articles/PMC12636994/
[22] Sosne G, Kleinman HK, Springs C. (Companion narrative review of the RGN-259 ARISE / SEER ophthalmic Phase II/III programmes for dry eye and neurotrophic keratopathy.) https://pmc.ncbi.nlm.nih.gov/articles/PMC9820614/
[23] Xu T, Tao S, Yu D, Wang J, Wang G, Wang M, Yao Z. Thymosin β4 enhances the healing of medial collateral ligament injury in rat. Regulatory Peptides. 2013;184:1-5. https://pubmed.ncbi.nlm.nih.gov/23523891/
[24] Xing Y, Ye Y, Zuo H, Li Y. Progress on the function and application of thymosin β4. Frontiers in Endocrinology. 2021;12:767785. https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.767785/full
[25] Goldstein AL, Hannappel E, Sosne G, Kleinman HK. Thymosin β4: a multi-functional regenerative peptide. Basic properties and clinical applications. Expert Opinion on Biological Therapy. 2012;12(1):37-51. https://pubmed.ncbi.nlm.nih.gov/22074294/
[26] U.S. Food and Drug Administration. Pharmacy Compounding Advisory Committee Meeting Materials — TB-500 (Thymosin Beta-4 fragment, free base and acetate) Section 503A Bulks List nomination. Docket FDA-2025-N-6895. Scheduled review 23 July 2026. https://www.fda.gov/advisory-committees/pharmacy-compounding-advisory-committee
[27] 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/
[28] Cha HJ, Jeong MJ, Kleinman HK. Role of thymosin beta4 in tumor metastasis and angiogenesis. J Natl Cancer Inst. 2003;95(22):1674-1680. https://pubmed.ncbi.nlm.nih.gov/14625258/
[29] 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;7(3):422-427. https://pubmed.ncbi.nlm.nih.gov/18094619/
[30] 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;1268:102-111. https://pubmed.ncbi.nlm.nih.gov/23084823/
[31] 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;5(2):e8976. https://pubmed.ncbi.nlm.nih.gov/20126456/
[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;15(4):427-438. https://pubmed.ncbi.nlm.nih.gov/36482504/

---

An independent editorial console for the peer-reviewed record — not a clinic, not a vendor, not medical advice.