# TB-500 References: the Cited Thymosin Beta-4 and Fragment Literature

> TB-500 references: the full citation register behind every quantitative claim on this site, with DOIs and PubMed links for the thymosin beta-4 and Ac-LKKTETQ literature.

The thymosin beta-4 and Ac-LKKTETQ literature this digest draws on, with DOIs and PubMed links. Source molecule is noted where a finding used the full-length parent protein.

## How to read this register

Every quantitative claim on this site maps to a numbered entry below. The regulatory facts on the [TB-500 legal status and FDA 503A category](/legal-status) page are cited to FDA primary sources (entries 16-18). Where a research finding used full-length thymosin beta-4 rather than the `Ac-LKKTETQ` fragment, the body copy carries that flag — the identity caveat is the spine of this whole digest, and it is preserved in how each study is described. The full citations follow in the references list.

## What each entry is, and what it is not

The register sorts into three layers. The **mechanistic anchor** is the actin-sequestration structure — the gelsolin-domain-1–thymosin beta-4 hybrid resolved to `2 Å` that established 1:1 G-actin capping [1] — together with the consolidating review of thymosin beta-4 biology [5]. The **repair and signaling findings** are the wound, cardiac, neurological, angiogenic, and matrix-remodeling studies [2][3][4][10][11][12][13], almost all of which used the full-length parent protein in animals or in vitro. The **safety and null layer** is what keeps the picture honest: the tumor-metastasis and pancreatic-cancer overexpression findings [7][8], the `mdx`-mouse result with more regenerating fibers but no strength gain [9], and the porcine ischemia-reperfusion null [14].

Two entries do work that the rest cannot. The Phase 1 intravenous study [6] is the only randomized, placebo-controlled human safety dataset here — and it is for full-length thymosin beta-4, not the fragment. The 2026 Sports Medicine review [15] is the current secondary read on where TB-500 and its peers sit: favorable animal tissue-repair signals, scarce human safety data, largely outside regulatory oversight. None of these entries is a clinical endorsement, and none establishes efficacy of the `Ac-LKKTETQ` heptapeptide in humans [5]. They are the published record, listed so any claim on this site can be checked against its source.

## References

[1] Irobi E, et al. Structural basis of actin sequestration by thymosin-beta4: implications for WH2 proteins. EMBO J. 2004;23(18):3599-3608. https://pubmed.ncbi.nlm.nih.gov/15329672/
[2] Bock-Marquette I, et al. Thymosin beta4 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/
[3] Malinda KM, et al. Thymosin beta4 accelerates wound healing. J Invest Dermatol. 1999;113(3):364-368. https://pubmed.ncbi.nlm.nih.gov/10469335/
[4] Morris DC, et al. A dose-response study of thymosin β4 for the treatment of acute stroke. J Neurol Sci. 2014;345(1-2):61-67. https://pubmed.ncbi.nlm.nih.gov/25060418/
[5] 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. https://pubmed.ncbi.nlm.nih.gov/22074294/
[6] Ruff D, et al. A randomized, placebo-controlled, single and multiple dose study of intravenous thymosin β4 in healthy volunteers. Ann N Y Acad Sci. 2010;1194:223-229. https://pubmed.ncbi.nlm.nih.gov/20536472/
[7] 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/
[8] 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):419-423. https://pubmed.ncbi.nlm.nih.gov/18094619/
[9] 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(1):e8976. https://pubmed.ncbi.nlm.nih.gov/20126456/
[10] Jo JO, et al. Thymosin β4 induces the expression of vascular endothelial growth factor (VEGF) in a hypoxia-inducible factor (HIF)-1α-dependent manner. Biochim Biophys Acta. 2010;1803(11):1244-1251. https://pubmed.ncbi.nlm.nih.gov/20691219/
[11] Qiu P, et al. Thymosin beta4 promotes matrix metalloproteinase expression during wound repair. J Cell Physiol. 2006;208(1):165-173. https://pubmed.ncbi.nlm.nih.gov/16607611/
[12] Sosne G, et al. Thymosin beta 4 suppression of corneal NFkappaB: a potential anti-inflammatory pathway. Exp Eye Res. 2007;84(4):663-669. https://pubmed.ncbi.nlm.nih.gov/17254567/
[13] Stark C, et al. Cardioprotection by systemic dosing of thymosin beta four following ischemic myocardial injury. Front Pharmacol. 2013;4:149. https://pubmed.ncbi.nlm.nih.gov/24348421/
[14] Stark C, et al. Systemic Dosing of Thymosin Beta 4 before and after Ischemia Does Not Attenuate Global Myocardial Ischemia-Reperfusion Injury in Pigs. Front Pharmacol. 2016;7:115. https://doi.org/10.3389/fphar.2016.00115
[15] 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/
[16] U.S. Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding That May Present Significant Safety Risks (entry: 'Thymosin beta-4, fragment (LKKTETQ), also known as TB-500'; Category 2, effective with the September 29, 2023 nominated-substances update). https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks
[17] 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; bulks-list nomination and PCAC evaluation process). https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act
[18] U.S. Food and Drug Administration. July 23-24, 2026: Meeting of the Pharmacy Compounding Advisory Committee (published agenda listing '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). https://www.fda.gov/advisory-committees/advisory-committee-calendar/july-23-24-2026-meeting-pharmacy-compounding-advisory-committee-07232026

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A forest-console reading of the TB-500 record — the Ac-LKKTETQ fragment held against thymosin beta-4 study by study, every confirmed finding logged green and every full-length-protein substitution flagged, with no clinic behind the console and nothing here dispensed or sold.