TB-500: what has been measured about safety

TB-500 is a seven residue acetylated fragment of a 43 residue protein, and its safety record consists of two federal database searches and one agency review, each worth reading at source rather than through a summary. FDA's Office of Surveillance and Epidemiology searched the FAERS adverse event database for reports naming TB-500 through 26 March 2025 and retrieved none, and the agency's literature search identified no cases either [20].

FDA attached its own footnote to that result and the footnote is the important half: reporting to FAERS is voluntary, there is no certainty that a reported event was caused by the suspect product, the agency does not receive all reports that may occur, especially for compounded products, and considering those limits it cannot draw definitive conclusions about the safety of TB-500.

One rule governs how everything below is read, and it is the same rule that sets this compound's grade. TB-500 is a seven residue acetylated fragment of a 43 residue protein, thymosin beta-4, and the parent has a real clinical programme behind it. Evidence about the parent never answers a question about the fragment. That cuts both ways here: the parent's trials cannot reassure anyone about TB-500, and the parent's biology cannot convict it either.

What this page reports, and what it does not

We report what has been documented. We do not prescribe what should be done.

Every sentence below reports what a named source measured or searched, in what system, and what it found. Where the answer is that nobody has looked, the page says which study would have looked and names the document recording that it was not done.

This page publishes no dose, no schedule, no route instruction and no list of people who should avoid anything. A list of who should not use a compound is a directions-for-use document, and it only makes sense if the reader is going to use the thing. What replaces it is a description of the compound and its record, written about the molecule rather than about the reader.

What has been measured

What the federal searches returned, and what they can support

FAERS holds no adverse event report naming TB-500 as the suspect product, through 26 March 2025, and FDA's literature search identified no published cases [20]. That is the headline, and two further records sit under it that are usually left out.

Two of them sit in a different FDA system: a search of the Human Foods Complaint System from 1 January 2004 to 10 March 2025 returned two cases naming a blended TB-500 and BPC-157 product, neither carrying any safety assessment. The third is filed under another compound. In the BPC-157 half of the same advisory committee presentation, one FAERS report describes a 40-year-old woman taking both products who developed diffuse hyperpigmentation and gingival darkening, which returned when she took them again.

Put together, the record is narrower than the headline and less empty than it. FAERS holds nothing under this compound's name, and it also holds a report filed against BPC-157 in which this compound was taken alongside and a finding recurred on re-exposure. A second FDA system, the Human Foods Complaint System, holds two unassessed complaints about a blend. None of that amounts to a safety profile, which is the agency's own conclusion rather than this page's.

The toxicology record is empty, in a checkable way

FDA's evaluation records that the nominator did not submit, and the agency did not identify, nonclinical toxicity studies of TB-500 free base or TB-500 acetate. That covers acute toxicity, repeat-dose toxicity, genotoxicity, developmental and reproductive toxicity, and carcinogenicity [20].

No animal study of this compound set out to look for harm either. One measured how a rat tendon healed [4], two measured how much compound was present and what it broke into [5] [10], and one measured how long it stays detectable in horses [6]. Those are four different questions and none of them is the toxicology question, so nothing in them can stand in for an answer to it.

Nothing describes what repeated exposure does over time, in any species. The longest anyone has given this compound to anything in a published experiment is four weeks, to eight rats.

Immunogenicity, the one hazard FDA names specifically

FDA's language in the briefing document is that peptides given by injectable routes may pose a significant risk for immunogenicity, potentially amplified by aggregation and by potential peptide-related impurities, and that the nomination did not include and FDA has not identified information suggesting these substances do not present such risks [20].

Aggregation is the word carrying that concern, and it translates simply. Peptides can stick to one another into larger particles, and a larger particle is likelier to draw an immune response than a single small molecule is; leftovers from synthesis can have the same effect. Neither has been tested for this fragment, which is why the agency's sentence names possibilities rather than results.

Two things belong beside it. The agency wrote may pose, which records a possibility it has not excluded rather than an outcome it has seen. And the same concern appears on a second FDA record, the 503A category 2 listing, which adds a further absence: no human exposure data has been identified for products containing this fragment at all [24].

What is actually in the vial

FDA concludes that both the free base and the acetate are not physically and chemically well characterized, and gives its reasons: naming outside the INN, USAN and IUPAC standards, and no public data on impurities, aggregates, microbial bioburden or bacterial endotoxin. Neither form has a USP or NF monograph, and neither is a component of any approved drug product [20].

The paperwork submitted to the agency demonstrates the problem better than any description of it. FDA lists four ways the nomination package contradicts itself: it nominates the free base and attaches a certificate of analysis for the acetate, that certificate's CAS number, formula and molecular weight are the acetate's, the formula stated in the package matches neither substance, and a second CAS number in the package matches neither either.

The container is a separate question from the paperwork, and one published analysis measured what is in products sold under this name [9]. What follows for safety is that an impurity profile cannot be described for a substance whose composition is described more than one way, which is exactly the gap FDA names when it raises aggregates and peptide-related impurities. [In-vitro] [9] [20]

Why the parent protein's record answers none of this

Thymosin beta-4 has been given to people in registered trials, including phase 2 and phase 3 ophthalmic programmes, and those trials carry safety data of their own [11] [12] [13] [27]. It is the single most common move in writing about TB-500 to borrow that record, and it is the single most common error.

Two molecules, two evidence bases. Thymosin beta-4 is a 43 residue protein and TB-500 is a seven residue acetylated fragment of it, and FDA's own stated position is that a profile obtained with the plain heptapeptide does not carry across to the acetylated one. No published experiment has compared the acetylated and plain forms side by side.

So the parent's trials establish nothing about the fragment's safety, and this page counts none of them. That is the same rule that sets this compound's evidence grade, which the full review derives and explains, and it is worth stating in the direction people rarely state it: the rule refuses reassurance from the parent's record exactly as firmly as it would refuse alarm from it.

Cancer, and the organ questions readers arrive with

The most common safety question about this compound is whether it causes cancer, and it deserves a direct answer rather than a hedge. The answer has three parts: what has been tested, why the question gets asked at all, and what the parent protein's literature does and does not license anyone to conclude.

Cancer

No study has tested whether TB-500 affects tumour growth, in any species, by any route. The study type that would is the carcinogenicity study, and FDA records that none was submitted and none was found for either the free base or the acetate [20]. There is no positive finding and there is no negative finding, because the experiment has not been done.

Why the question gets asked is worth answering plainly, because the reasoning behind it is not silly. New blood vessel growth is on the marketed claim set for this compound, compiled by FDA from fourteen vendor and clinic websites [20], and growing new blood vessels is a process a tumour also depends on. That is the inference readers are making, and it is an inference from a marketing claim rather than from a measurement: nothing in the published record establishes that TB-500 promotes new blood vessel growth in a person in the first place.

The parent protein cannot settle it either, in either direction. Work attributing new blood vessel growth and cell migration to a stretch inside thymosin beta-4 [2] [3], and work reporting that the parent protein blocks activation and movement of one human cell type [15], are studies of a 43 residue protein. Neither administered TB-500, and evidence about a different molecule never sets this compound's answer. So the honest statement is the narrow one: nothing published tests whether TB-500 affects tumour growth, and nothing published establishes the mechanism the worry is built on. [Anecdote] [20]

Liver, kidney, heart and everything else

No study of TB-500 in any species reports a liver enzyme, a kidney marker, an organ weight or histopathology of any organ. The study type that collects all of those as a matter of routine is the repeat-dose toxicity study, and it is one of the five FDA records as absent [20].

The animal work that does exist looked at three things and none of them was an organ panel: tendon healing in rats [4], compound concentrations in metabolism experiments [5] [10], and detection windows in horses [6]. Serum chemistry, urinalysis and histology appear in none of them.

So the answer for every organ is the same answer, and it comes from the same absence rather than from a reassuring result. Nothing has been measured, in any organ, in any species.

What has not been characterised

Set out plainly, so the shape of the gap is visible rather than implied. Nothing is published on what a single large exposure does, what daily exposure does over weeks or months, whether the molecule affects DNA, what it does in pregnancy or to offspring, or whether lifetime exposure produces tumours [20]. No human being has received TB-500 under any protocol, so there is no clinical exposure record at all.

Nothing is published on the impurity profile, the aggregate content, the microbial bioburden or the endotoxin level of either form, and FDA states that no such data exists in the public literature [20]. Nothing is published on interaction with any other substance.

Two things follow, and only two. This page cannot describe the risks of TB-500, because the studies that would describe them do not exist. And nobody else can describe its safety either, from the same absence, whatever a product page or a registry record says.

Our takeTwo empty federal databases are the most quoted thing about this compound and the least informative. FDA searched FAERS and the literature, found nothing, and wrote in the same document that it cannot draw definitive conclusions about the safety of TB-500 from that result. The other thing worth knowing is what the record does not contain: the one registry record naming this compound says of itself that it is a fictional example, so nothing is in progress that would fill any of this in.

Talk to a licensed clinician about anything concerning your health.

Frequently asked questions

References

1. Esposito S, Deventer K, Goeman J, Van der Eycken J, Van Eenoo P. Synthesis and characterization of the N-terminal acetylated 17-23 fragment of thymosin beta 4 identified in TB-500, a product suspected to possess doping potential. Drug Test Anal. 2012. PMID 22962027 DOI 10.1002/dta.1402
2. Sosne G, Qiu P, Goldstein AL, Wheater M. Biological activities of thymosin beta4 defined by active sites in short peptide sequences. FASEB J. 2010. PMID 20179146 DOI 10.1096/fj.09-142307
3. Philp D, Badamchian M, Scheremeta B, Nguyen M, Goldstein AL, Kleinman HK. Thymosin beta 4 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. PMID 12581423 DOI 10.1046/j.1524-475x.2003.11105.x The peptide arm used the non-acetylated heptapeptide LKKTETQ, which is not the molecule sold as TB-500
4. Biçer O, Adanir O, Güleryüz Y, Balci EC, Dinçel YM, Yenigün MY, Aydin C, Bayrak BY. Effects of BPC-157 and TB-500 on Achilles tendon healing in rats: A histopathological and biomechanical study. Jt Dis Relat Surg. 2026. PMID 42542926 DOI 10.52312/jdrs.2026.2951
5. Rahaman KA, Muresan AR, Min H, Son J, Han HS, Kang MJ, Kwon OS. Simultaneous quantification of TB-500 and its metabolites in in-vitro experiments and rats by UHPLC-Q-Exactive orbitrap MS/MS and their screening by wound healing activities in-vitro. J Chromatogr B Analyt Technol Biomed Life Sci. 2024. PMID 38382158 DOI 10.1016/j.jchromb.2024.124033
6. Ho EN, Kwok WH, Lau MY, Wong AS, Wan TS, Lam KK, Schiff PJ, Stewart BD. 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. PMID 23084823 DOI 10.1016/j.chroma.2012.09.043
7. Lu P, Shan M, Peng C, Ji W, Yang T, Yang Z, Zhang Z, Wang Y. Alkaline Phosphatase-Triggered Spatiotemporal Repair of Corneal Injury with TB500 Peptide Hydrogel. ACS Appl Mater Interfaces. 2025. PMID 41359360 DOI 10.1021/acsami.5c14652 Administered as a covalent peptide conjugate that self-assembles into a gel, not as free TB-500
8. Ou H, Chen R, Zhou L, Zhang Y, Zhao S, Yang Z. Thymosin β4-derived peptides alleviate neuroinflammation and neurite atrophy in both in vitro models and in vivo 5 × FAD mice: A potential therapy for memory improvement in Alzheimer's disease. Int Immunopharmacol. 2026. PMID 41443105 DOI 10.1016/j.intimp.2025.116097 TB500 is reported together with Ac-SDKP throughout; no arm isolates either peptide
9. Delcourt V, Garcia P, Chabot B, Barnabé A, Bouscarel M, Loup B, Popot MA, Bailly-Chouriberry L. TB500/TB1000 and SGF1000: A scientific approach for a better understanding of misbranded and adulterated drugs. Drug Test Anal. 2023. PMID 36482504 DOI 10.1002/dta.3421
10. Zvereva I, Semenistaya E, Krotov G, Rodchenkov G. Comparison of various in vitro model systems of the metabolism of synthetic doping peptides: Proteolytic enzymes, human blood serum, liver and kidney microsomes and liver S9 fraction. J Proteomics. 2016. PMID 27569051 DOI 10.1016/j.jprot.2016.08.016
11. 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. PMID 25826322 DOI 10.1097/ICO.0000000000000379 A trial of thymosin beta-4, the parent protein, not of TB-500
12. 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. PMID 26056426 DOI 10.2147/OPTH.S80954 A trial of thymosin beta-4, the parent protein, not of TB-500
13. Sosne G, Kleinman HK, Springs C, Gross RH, Sung J, Kang S. 0.1% RGN-259 (Thymosin ß4) 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. PMID 36613994 DOI 10.3390/ijms24010554 A trial of thymosin beta-4, the parent protein, not of TB-500
14. Sosne G. Thymosin beta 4 and the eye: the journey from bench to bedside. Expert Opin Biol Ther. 2018. PMID 30063853 DOI 10.1080/14712598.2018.1486818 Indexed by PubMed as a review and a personal narrative, not as a study
15. Shah R, Reyes-Gordillo K, Rojkind M. Thymosin β4 inhibits PDGF-BB induced activation, proliferation, and migration of human hepatic stellate cells via its actin-binding domain. Expert Opin Biol Ther. 2018. PMID 30063851 DOI 10.1080/14712598.2018.1478961 Cell work on the parent protein. One of the three references submitted with the nomination
16. Nguyen J, Verma S, Vuong VT, Queener H, Coulson-Thomas VJ, Gesteira TF. Engineered Tandem Thymosin Peptide Promotes Corneal Wound Healing. Invest Ophthalmol Vis Sci. 2025. PMID 41235866 DOI 10.1167/iovs.66.14.31 An engineered dual-domain molecule, distinct from both TB-500 and the parent protein
17. Mendias CL, Awan TM. Safety and Efficacy of Approved and Unapproved Peptide Therapies for Musculoskeletal Injuries and Athletic Performance. Sports Med. 2026. PMID 41966639 DOI 10.1007/s40279-026-02437-0
18. Mayfield CK, Bolia IK, Feingold CL, Lin EH, Liu JN, Rick Hatch GF, Gamradt SC, Weber AE. Injectable Peptide Therapy: A Primer for Orthopaedic and Sports Medicine Physicians. Am J Sports Med. 2026. PMID 41476424 DOI 10.1177/03635465251357593
19. Rahman OF, Lee SJ, Seeds WA. Therapeutic Peptides in Orthopaedics: Applications, Challenges, and Future Directions. J Am Acad Orthop Surg Glob Res Rev. 2026. PMID 41490200 DOI 10.5435/JAAOSGlobal-D-25-00236
20. US Food and Drug Administration. TB-500 (free base) and TB-500 acetate. Briefing document for the Pharmacy Compounding Advisory Committee, dated 15 May 2026, 41 pages, downloaded with a browser user agent and read in full on 9 August 2026 with the page count checked against the file. Carries the identity data, the nomination history, the marketed-claims inventory, the acetylation caveat, the FAERS and complaint-system searches, and the agency's proposal against adding either form to the 503A Bulks List. FDA advisory committee materials. 2026. Briefing document
21. US Food and Drug Administration. July 23, 2026 Meeting of the Pharmacy Compounding Advisory Committee: FDA Presentations. 149 pages, page count checked against the file, read on 9 August 2026. The TB-500 evaluation runs from deck page 89 to deck page 118. Numbering inside that section restarts, so its slide 19 is deck page 107 and carries the effectiveness conclusion, its slide 21 is deck page 109 and carries the adverse event search with its footnote, and its slide 26 carries the WADA class. The companion deck for 24 July contains no TB-500 content. FDA advisory committee materials. 2026. FDA presentations
22. US Food and Drug Administration. Questions for PCAC regarding whether FDA should include certain bulk drug substances on the 503A Bulks List, Pharmacy Compounding Advisory Committee, 23 and 24 July 2026. 2 pages, read in full. Item 3 of the 23 July afternoon session is TB-500-related bulk drug substances, on two voting questions covering the free base and the acetate. FDA advisory committee materials. 2026. Voting questions
23. Office of the Federal Register. Pharmacy Compounding Advisory Committee; Notice of Meeting; Establishment of a Public Docket; Request for Comments. Bulk Drug Substances Nominated for Inclusion on the Section 503A Bulk Drug Substances List. Document 2026-07361, published 16 April 2026, Docket No. FDA-2025-N-6895. Its chart of evaluated uses records wound healing for TB-500 free base and TB-500 acetate. Federal Register. 2026. Notice of meeting
24. US Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. The category 2 table carries the row Thymosin beta-4, fragment (LKKTETQ), also known as TB-500, with the immunogenicity and aggregation rationale and the statement that FDA has not identified any human exposure data for drug products containing the fragment. Page content current 22 April 2026, read 9 August 2026. FDA human drug compounding. 2026. Category 2 record
25. Hudson Biotech. A Phase 1/2, Randomized, Double-Blind, Placebo-Controlled, Sequential Dose-Escalation Study of TB-500 (Thymosin Beta 4 17-23 Fragment) in Adults With Stable Atherosclerotic Cardiovascular Disease. Registry record read in full through the ClinicalTrials.gov API v2 on 9 August 2026: recruiting, actual start 5 February 2026, first posted 23 March 2026, 80 participants estimated, no results posted. Its registered brief summary begins: this fictional study is an example of a ClinicalTrials.gov-style record. ClinicalTrials.gov, NCT07487363. 2026. Registry record
26. US National Library of Medicine, ClinicalTrials.gov. Registry searches run through API v2 on 9 August 2026. A term search for thymosin beta 4 returned 18 records, of which 17 registered the parent protein or a recombinant version of it, across dry eye, neurotrophic keratopathy, venous stasis ulcers, pressure ulcers, epidermolysis bullosa, corneal wounds in diabetes and acute myocardial infarction, and none in tendon, muscle or ligament. A sponsor search for Hudson Biotech returned 8 records, all recruiting, all first posted between 27 February and 1 April 2026, all single-site at Peking University Shenzhen Hospital, three of which state in their own registered text that they are example records. ClinicalTrials.gov. 2026. Registry searches
27. ReGenTree, LLC. Assessment of the Safety and Efficacy of RGN-259 Ophthalmic Solutions in Dry Eye (ARISE-2). Registry record with posted results, read through the ClinicalTrials.gov API v2 on 9 August 2026: phase 3, 601 participants actual, completed March 2018. Both primary endpoints are change from baseline at day 29 on scales where a higher score is worse; ocular discomfort moved plus 0.07 against minus 0.04 on placebo and corneal fluorescein staining plus 0.07 against minus 0.01. No statistical test is posted alongside them. ClinicalTrials.gov, NCT02974907. 2018. Posted results
28. World Anti-Doping Agency. The 2026 Prohibited List, World Anti-Doping Code International Standard, effective 1 January 2026. Class S2, peptide hormones, growth factors, related substances and mimetics, is prohibited at all times and its heading states that all prohibited substances in the class are non-Specified Substances. On page 8, class S2.3, growth factors and growth factor modulators, carries the entry Thymosin-ß4 and its derivatives e.g. TB-500. Read back from the final English document, 26 pages, retained off-site: the address below serves a zero-byte response to automated requests and is recorded as such in this repository's source ledger. WADA. 2026. Prohibited List
29. National Center for Biotechnology Information. TYB4_HUMAN, Thymosin beta-4, accession P62328. Protein record read on 9 August 2026: a 44 residue precursor, MSDKPDMAEIEKFDKSKLKKTETQEKNPLPSKETIEQEKQAGES, whose annotated mature chain runs residues 2 to 44 and gives the 43 residue protein. Counting from the first serine of that mature chain, residues 17 to 23 are LKKTETQ. NCBI Protein. 2026. Protein record