TB-500 Fragment 17-23

The seven-amino-acid actin-binding segment of thymosin beta-4 (residues 17-23, LKKTETQ), sold on the research market in N-acetylated form as a smaller synthetic stand-in for the full 43-amino-acid parent peptide.

Also referenced as: TB-500 Fragment, TB-500 Frag 17-23, TB4-Frag, LKKTETQ, Ac-LKKTETQ, N-acetylated LKKTETQ, Thymosin Beta-4 Fragment 17-23

What is TB-500 Fragment 17-23?

TB-500 Fragment 17-23 is a synthetic heptapeptide with the sequence Leu-Lys-Lys-Thr-Glu-Thr-Gln (LKKTETQ), corresponding exactly to residues 17 through 23 of human thymosin beta-4. The free peptide has the formula C36H66N10O13 and a molecular weight of about 847 Da; research-market material is almost always the N-terminally acetylated form, Ac-LKKTETQ (C38H68N10O14), at about 889 Da. That acetyl group is a synthetic addition, not a piece of the parent molecule — native thymosin beta-4 is acetylated at Ser1, so the acetyl on Leu17 exists only in the fragment.

The parent, thymosin beta-4, is a 43-amino-acid, roughly 4.9 kDa polypeptide and the main G-actin-sequestering peptide in mammalian cells. It is predominantly intracellular but is found in essentially all cells and body fluids, and the activities this fragment is sold for — angiogenesis, cell migration, wound repair — are extracellular ones. The parent carries several functionally distinct regions: an N-terminal tetrapeptide (Ac-SDKP, residues 1-4) associated with anti-inflammatory and antifibrotic effects, and the central actin-binding region that this fragment reproduces (Sosne et al., FASEB Journal, 2010;24(7):2144-2151). Reducing a 43-residue protein to seven residues puts it within easy reach of routine solid-phase synthesis, which is the practical reason it exists as a separate catalog item at all.

The name is where most of the confusion starts. PeptideBenchmark tracks a separate TB-500 listing because the market uses “TB-500” for two different molecules: the original veterinary preparation sold under that name was confirmed by mass spectrometry to contain N-acetylated LKKTETQ as its key ingredient (Esposito et al., Drug Testing and Analysis, 2012;4(9):733-738; Ho et al., Journal of Chromatography A, 2012;1265:57-69), while much of what is sold as “TB-500” today is full-length 43-amino-acid thymosin beta-4. Listings labeled “Fragment 17-23,” “Frag 17-23,” or “TB4-Frag” are the ones explicitly claiming the heptapeptide.

How it works

• Actin binding. Mutational mapping of thymosin beta-4 located its actin contacts in two separable structural units: an N-terminal region (residues 1-16) that must adopt an alpha-helix to bind actin, and a short hexapeptide motif at residues 17-22, with Lys18 identified as an important electrostatic contact (Van Troys et al., EMBO Journal, 1996;15(2):201-210). The marketed fragment is that motif plus the adjacent Gln23. The parent’s full actin-sequestering activity requires both units, so the isolated motif reproduces a contact site rather than the complete sequestering unit.
• Angiogenesis and endothelial migration. Using natural thymosin beta-4, proteolytic fragments, and synthetic peptides, the seven-amino-acid actin-binding motif was shown to be essential for the parent’s angiogenic activity: it matched full-length thymosin beta-4 at roughly 50 nM in human umbilical vein endothelial cell migration and chick aortic arch sprouting assays, while peptides missing any part of the motif were inactive. The same heptapeptide blocked cell adhesion to thymosin beta-4, marking it as the parent’s major cell-binding site (Philp et al., FASEB Journal, 2003;17(14):2103-2105).
• Dermal repair in impaired-healing models. In 26-month-old mice, the LKKTETQ synthetic peptide promoted wound repair comparably to the parent molecule, which itself increased keratinocyte migration, wound contracture, and collagen deposition in those aged animals (Philp et al., Wound Repair and Regeneration, 2003;11(1):19-24; parent-molecule wound data in Malinda et al., Journal of Investigative Dermatology, 1999;113(3):364-368).
• Rapid proteolysis, with activity attributed to a metabolite. In human serum, enzyme systems, and dosed rats, Ac-LKKTETQ is cleaved quickly: Ac-LK was the dominant early metabolite and Ac-LKK persisted to 72 hours. In fibroblast wound-healing assays, only the intermediate Ac-LKKTE showed significant activity, leading the authors to suggest that reported wound-healing effects of TB-500 may be attributable to that metabolite rather than to the administered peptide (Rahaman et al., Journal of Chromatography B, 2024;1235:124033).

Research status

There are no human trials of this fragment. No completed, ongoing, or planned clinical study evaluates LKKTETQ or Ac-LKKTETQ in people. The FDA stated plainly, when it placed the substance in category 2 of its compounding bulk-substance review, that it had identified no human exposure data for drug products containing thymosin beta-4 fragment.

One caution about searching the registry: a ClinicalTrials.gov record exists under NCT07487363, titled as a Phase 1/2 study of “TB-500 (Thymosin Beta 4 17-23 Fragment)” in stable atherosclerotic cardiovascular disease. It is listed as recruiting, carries an industry sponsor name and an estimated 2028 completion date, and looks entirely unremarkable in a list of search results. Its own brief summary, however, opens by stating that it is a fictional study posted as an example of a ClinicalTrials.gov-style record; its detailed description says the dose levels are not provided because the record is a public example; and it is flagged as not an FDA-regulated drug. It is not evidence of a real trial program, and it should not be cited as one.

The parent molecule has the trial record; the fragment does not. Every registered clinical program under the thymosin beta-4 heading used full-length peptide, not the 17-23 fragment. RegeneRx and ReGenTree ran Phase 2 studies in pressure ulcers (NCT00382174, 72 participants, completed) and venous stasis ulcers (NCT00832091, 72 participants, completed), and two large Phase 3 dry-eye studies of RGN-259 ophthalmic solution (NCT02974907, 601 participants, completed 2018; NCT03937882, 700 participants, completed 2021). A further Phase 3 of the same ophthalmic solution is recruiting in a different indication, neurotrophic keratopathy (NCT05555589, 70 participants estimated). The failures are part of the record: a Phase 2 study in epidermolysis bullosa was terminated, with the registry listing lack of patient availability and expiration of study drug (NCT00311766); a Phase 2 of injectable thymosin beta-4 for acute myocardial infarction was withdrawn as never initiated (NCT01311518); and a Phase 1 intravenous safety study was withdrawn without enrolling, the registry citing contract manufacturing issues (NCT00743769). Separately, a recombinant human thymosin beta-4 injection has completed Phase 1 studies in healthy volunteers (NCT04555824, NCT04555850) and Phase 2 studies in acute myocardial infarction (NCT05485818, NCT05984134) in China. No thymosin beta-4 product, full-length or fragment, holds FDA approval.

Preclinical work on the fragment itself is thin and mostly old. The two 2003 Philp papers, both from the same NIH group, remain the primary direct evidence. More recent work is formulation-focused rather than clinical: an alkaline-phosphatase-triggered, self-assembling peptide hydrogel incorporating the LKKTETQ sequence accelerated epithelial regeneration in a corneal alkali-burn model, described by its authors as the first ocular application of the sequence (Lu et al., ACS Applied Materials & Interfaces, 2025;17(50):67503-67518).

Animal studies labeled “TB-500” often do not identify which molecule was used. A rat Achilles tendon transection-and-repair model (32 rats, eight per group) reported that a group dosed at 60 µg/kg/day intraperitoneally for four weeks reached significantly higher maximum load to failure and significantly better Bonar and Movin histopathological scores than controls, with no additional benefit from combining it with BPC-157 (Biçer et al., Jt Dis Relat Surg, 2026;37(3):822-837). The report identifies the agent only as “synthetic thymosin beta-4 (TB-500)” — a recurring ambiguity that makes much of the “TB-500” animal literature hard to assign to either listing. A 2026 narrative review of peptides in sports medicine treats Tβ4 and TB-500 as separate entries for exactly this reason, and concludes that rigorous human safety data across this class is scarce (Mendias & Awan, Sports Medicine, 2026;56(8):1921-1935).

Common dosage forms

Research suppliers list this compound as lyophilized powder in sealed glass vials, most commonly at 10 mg per vial, sold singly or in multi-vial kits, and reconstituted in the laboratory with bacteriostatic or sterile water. Multi-peptide recovery blends are frequently sold with “TB-500” on the label alongside compounds such as BPC-157, but those labels almost never state which molecule is present, so a blend cannot be assumed to contain the heptapeptide rather than full-length thymosin beta-4. There is no FDA-approved product and no legitimate pharmacy-compounded form: the substance appears on neither the 503A nor the 503B bulks list, and the nomination that would have added it was withdrawn before FDA completed its review. Topical and hydrogel presentations exist only in published laboratory work, not as commercial formats.

Key considerations

• Regulatory status. FDA’s page on bulk drug substances that may present significant safety risks names “Thymosin beta-4, fragment (LKKTETQ), also known as TB-500” and sets out the agency’s rationale: potential immunogenicity from aggregation and peptide-related impurities, no identified human exposure data, and insufficient information to know whether the substance would cause harm in humans. That rationale still appears on the page, but as of its April 2026 revision the entry sits in the “bulk drug substances nominated but withdrawn” table rather than the active category 2 table — FDA describes these substances as previously in category 2, with the nominations withdrawn by the nominators. The practical position is unchanged: withdrawal ended the review that could have placed the substance on a bulks list, so it remains ineligible for pharmacy compounding, and the removal is a procedural step rather than any finding of safety.
• Prohibited in sport at all times. The WADA Prohibited List names “Thymosin-β4 and its derivatives e.g. TB-500” under S2.3, growth factors and growth factor modulators, which is prohibited both in and out of competition. Analytical work on detecting Ac-LKKTETQ and its metabolites in urine and plasma dates to 2012 — a proposed human screening strategy alongside a synthesized reference standard (Esposito et al., 2012), and a validated equine method confirmed in post-administration samples from dosed horses (Ho et al., 2012) — so this is a detectable substance, not a theoretical ban.
• The core evidence gap is whether the sold molecule is the active one. The direct fragment data is two 2003 papers from one laboratory, in mice and in cell assays, at nanomolar concentrations. The most recent pharmacology work found no significant wound-healing activity for the administered Ac-LKKTETQ itself in fibroblasts, with the effect appearing only in its Ac-LKKTE breakdown product — a result that complicates claims made for the sold molecule itself, and one that has not yet been independently replicated in either direction.
• Naming confusions are unusually dense here. Four separate distinctions matter: the fragment versus full-length thymosin beta-4 (both sold as “TB-500”); the 17-23 fragment versus Ac-SDKP, the residues 1-4 fragment with a different activity profile; the acetylated commercial form versus the unmodified LKKTETQ used in most published research; and the mapped actin-contact motif at residues 17-22 versus the seven-residue sequence including Gln23 that vendors sell. Product labels rarely make any of these explicit, and certificates of analysis are the only practical way to tell which molecule is in a given vial.
• Product-quality risk is the near-term safety issue. With no approved reference product and no human pharmacovigilance data, the identifiable risks are the ones FDA named — aggregation, peptide-related impurities, and immunogenicity — plus the ordinary hazards of unregulated supply, including identity substitution between the fragment and the full-length peptide, which independent testing cannot resolve unless the report states the measured mass.