TB-500 Fragment 17-23 Research, Specifications & Scientific Information

The TB-500 17-23 fragment is the seven-residue acetylated peptide Ac-Leu-Lys-Lys-Thr-Glu-Thr-Gln-OH, corresponding to the actin-binding motif at residues 17 to 23 of thymosin beta-4. It is the substance the chemical registers record under the name TB-500. It is not approved by the FDA for any indication.

By Published Updated

Category: Repair and regenerative research peptides

Introduction

This entry exists because a name collided with itself.

The chemical registers define TB-500 as a seven-residue acetylated peptide — Ac-Leu-Lys-Lys-Thr-Glu-Thr-Gln-OH, residues 17 to 23 of the protein thymosin β4 — with its own registry number, its own unique ingredient identifier and a mass of 889.0 g/mol. Much of the material supplied under the name TB-500 is instead the whole 43-residue protein, whose mass is about 5.6 times larger. Those are two substances, not two names, and the TB-500 entry in this library covers the protein. This page covers the fragment.

The fragment has a scientific interest independent of the naming problem, and it is a genuinely unusual one. Mapping work established that thymosin β4's actin-binding site is built from two separate structural pieces, and this fragment is only one of them [2]. In the assay that measures actin sequestration, pieces missing the other half do not work [1]. Yet in endothelial migration and vessel-sprouting assays the isolated seven-residue motif matched the whole protein almost exactly [6]. Whatever the motif is doing in those assays, it is not doing it by sequestering actin.

This page is a reference record. It describes research. It contains no guidance of any kind on handling the material.

What Is TB-500 Fragment 17-23?

A synthetic heptapeptide, acetylated at the N-terminus, with the sequence Ac-LKKTETQ-OH. It corresponds exactly to residues 17 through 23 of thymosin β4, a 43-residue intracellular protein of the β-thymosin family that is the principal G-actin-sequestering molecule in eukaryotic cells [4].

Within the literature the fragment goes by several descriptions that mean the same thing: the actin-binding domain peptide, the actin-binding motif, LKKTETQ, or thymosin β4 (17-23). One review describes it as the central actin-binding domain, residues 17 to 22, plus one additional amino acid — the terminal glutamine [7]. That description is worth keeping in mind, because the mapping literature consistently defines the motif as a hexapeptide at 17-22, and the seventh residue is an addition rather than part of the mapped site.

It is not an approved medicine anywhere. One clinical trial of the fragment as such is registered and recruiting, with no results [10].

TB-500 Fragment 17-23 Specifications

Compound name
TB-500 Fragment 17-23
Full chemical name
N-Acetyl-L-leucyl-L-lysyl-L-lysyl-L-threonyl-L-alpha-glutamyl-L-threonyl-L-glutamine
Aliases
Ac-LKKTETQ-OH, thymosin beta-4 (17-23), actin-binding domain peptide of thymosin beta-4, TB-500 (register definition), LKKTETQ
Development code
Not publicly characterised
CAS number
885340-08-9
PubChem CID
62707662
UNII
QHK6Z47GTG
Compound type
Synthetic N-acetylated heptapeptide
Peptide family
Beta-thymosin family fragment
Amino acid sequence
Ac-Leu-Lys-Lys-Thr-Glu-Thr-Gln-OH
Sequence length
7 residues
Molecular formula
C38H68N10O14
Molecular weight
889.0 g/mol
Primary target
Monomeric (G-)actin, as part of the parent protein's binding site; no receptor has been identified for the isolated fragment
Secondary targets
Cell-surface binding site on endothelial cells implicated in adhesion assays
Receptor family
Not publicly characterised
Agonist / antagonist status
Not established

This substance is the seven-residue N-terminally acetylated peptide Ac-Leu-Lys-Lys-Thr-Glu-Thr-Gln-OH, corresponding to residues 17 to 23 of thymosin beta-4. The FDA/NCATS Global Substance Registration System records it under UNII QHK6Z47GTG, under the name TB-500, with CAS registry number 885340-08-9, a cross-reference to PubChem compound identifier 62707662, and the acetyl group recorded as a structural modification on the leucine at position 1. PubChem carries the same compound with molecular formula C38H68N10O14 and an average mass of 889.0 g/mol. Two cautions follow. First, the register's own calculated mass for this record, 846.98, is computed from the unmodified seven-residue chain and does not include the acetyl group; the 889.0 figure from PubChem is the one that corresponds to the acetylated molecule. Second, the unacetylated free heptapeptide is a separate substance with its own PubChem compound identifier, 10169788, its own registry number, 476014-70-7, and an International Nonproprietary Name, and it differs from this one by 42 daltons. The name TB-500 is also widely applied to the 43-residue protein thymosin beta-4, which is a different substance of roughly 4963 g/mol; the separate entry for TB-500 in this library covers that protein and sets out how to tell the two apart. The certificate of analysis and the mass spectrometry result supplied with a laboratory order are the record of which molecule a given lot contains.

Values that a public register does not carry are shown as not publicly characterised rather than estimated. Identifiers are reference values; the certificate of analysis supplied with a laboratory order is the record for a given lot.

How Does TB-500 Fragment 17-23 Work?

There are two answers in the literature and they do not fit together neatly. This page reports both rather than choosing.

The actin account, which does not support the fragment. Thymosin β4 binds monomeric actin and prevents it polymerising. The binding site was mapped by mutational analysis to two separate structural entities: an N-terminal region spanning residues 1 to 16, which must adopt an α-helix and contacts actin through a hydrophobic patch, and a hexapeptide motif at residues 17 to 22. Electrostatic contacts from lysine 18 in the motif and lysine 14 in the helix both appeared important [2]. A fragment that carries the motif alone carries one contact point out of several, and the sequestration assay confirms the consequence: fragments lacking the N-terminal region failed to inhibit G-actin polymerisation [1].

The cell-activity account, which does. Using naturally occurring protein, proteolytic fragments and synthetic peptides, the seven-residue motif was identified as essential for angiogenic activity, with the isolated motif and the whole protein showing near-identical activity in the same assays [6]. Adhesion to thymosin β4 was blocked by the seven-residue peptide, which identifies the motif as the protein's major cell-binding site.

The reconciliation offered in that work is that the motif's cell-level activity is a binding function rather than a sequestering one — and the observation that soluble actin inhibited adhesion and sprouting suggests the same surface is involved in both [6]. No receptor has been identified. The specification table shows the primary target accordingly.

TB-500 Fragment 17-23 Mechanism of Action

In vitro research

The sequestration assay, and what it excludes

The DNase I inhibition assay reports monomeric G-actin and not filamentous F-actin, which makes it a direct readout of sequestration. In that assay, thymosin β4 sequestered G-actin at a one-to-one ratio and blocked its polymerisation in high-salt solution, and oxidation of the single methionine at position 6 did not abolish the property. Neither thymosin β4 13-43 nor thymosin β4 24-43 inhibited polymerisation at all, and the authors concluded that structural features before position 13 are obligatory for the function [1].

Residue 13 is the relevant boundary, and this fragment begins at residue 17.

The mapping study, and why the site has two halves

Chemically synthesised full-length variants were used with chemical cross-linking, native-gel complex formation, actin-sequestering experiments and circular dichroism. The model that emerged has the N-terminal part folding into an α-helix that contacts actin through a hydrophobic patch at residues 6 to 12, and the 17-22 motif contributing separately, with lysine 18 among the electrostatic contacts. The critical residues are conserved across the β-thymosin family, and a comparable pattern appears in the C-terminal headpieces of villin and dematin [2].

A site built from a helix and a motif is not reproduced by supplying the motif.

The angiogenesis study, and the dissociation it establishes

Endothelial migration assays with human umbilical vein endothelial cells and vessel sprouting assays using chick aortic arches were run against thymosin β4, its proteolytic fragments and synthetic peptides. The protein and the seven-residue actin-binding motif displayed near-identical activity at approximately 50 nM; peptides lacking any portion of the motif were inactive. Adhesion to thymosin β4 was blocked by the seven-residue peptide, and both adhesion and sprouting were inhibited by adding 5 to 50 nM soluble actin [6].

Two things follow. The motif is necessary and, in these assays, sufficient. And the same experiments that establish that show the motif has an actin-related surface, since free actin competes it away.

Where the fragment outperformed the other fragment

Human hepatic stellate cells activated by PDGF-BB were treated with two peptides derived from thymosin β4: the N-terminal Ac-SDKPDMAEIEKFDKS (residues 1-15) and this actin-binding LKKTETQ (residues 17-23). The 17-23 peptide, but not the 1-15 peptide, inhibited PDGF-BB-dependent upregulation of the PDGFβ receptor, α-smooth muscle actin and collagen 1, and blunted Akt phosphorylation at both Thr308 and Ser473, with downstream effects on PRAS40 phosphorylation and on proliferation and migration. The 1-15 peptide blocked Akt phosphorylation at Ser473 only, through mTOR, and had no effect on proliferation or migration. The authors concluded that the anti-fibrogenic actions of the parent protein are exerted via residues 17-23 [8].

This is a head-to-head comparison of two fragments of the same protein in the same assay, which is the most informative design available for a question of this kind.

What Is TB-500 Fragment 17-23 Being Researched For?

Mostly, it is used to answer questions about the protein it came from.

  • Structure-activity mapping within thymosin β4 — which part accounts for which property [1, 2, 7, 8].
  • Endothelial migration and vessel sprouting — the assays in which the isolated motif matched the parent protein [6].
  • Dermal repair in rodents — one comparison against the parent protein in aged animals [5].
  • Cardiovascular biomarkers — one registered human trial, recruiting, no results [10].

The clinical literature in this field — the ophthalmic trials, the dermatology trials, the cardiac work — used the full-length protein, and it belongs to the thymosin β4 entry rather than to this one [3, 9].

Human Research on TB-500 Fragment 17-23

Human clinical research

Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.

There is one trial, and it has produced nothing yet.

A phase 1/2 study registered in 2026 names the thymosin β4 17-23 fragment in its own registry title, carries a planned enrolment of 80, has cardiovascular biomarker endpoints in stable atherosclerotic cardiovascular disease, and is listed as recruiting [10]. No results are posted.

A registered trial is a statement of intent, not evidence. It establishes that a sponsor considers the question worth asking and that a protocol passed review. It establishes nothing about outcomes, and a page that treated a recruiting registration as a finding would be misreading the registry.

Everything else described as human research in this field used the 43-residue protein. Human cells in culture — the endothelial cells and hepatic stellate cells above — are in vitro work, tiered as such on this page.

Preclinical Research on TB-500 Fragment 17-23

Animal research

The in vivo record for the isolated fragment is one endpoint, in one model, in one paper.

Full-thickness dermal wounds were studied in db/db diabetic mice and in 26-month-old aged mice, in which repair is delayed. Thymosin β4 in saline or in a hydrogel increased wound contracture and collagen deposition in the diabetic animals; in the aged animals it increased keratinocyte migration as well. The relevant comparison for this page came last: the actin-binding domain, supplied as the seven-amino-acid synthetic peptide LKKTETQ, promoted repair in the aged animals comparably to the parent molecule [5].

The chick aortic arch sprouting assay described in the mechanism section is an ex vivo tissue preparation rather than a whole-animal study, and it belongs with the in vitro work.

That is the whole animal record for this fragment. It should be read for exactly what it reports — one model, one species, one age group, one tissue — and not extended.

Findings described in this section were observed in animals, and nothing in them establishes anything about humans.

Current Research Status

Regulatory status (United States)
Not approved. This peptide has not been approved by the U.S. Food and Drug Administration for any indication.
Investigational status
One clinical trial of the fragment as such has been identified: a phase 1/2 study registered in 2026 with cardiovascular biomarker endpoints and a planned enrolment of 80, recruiting, with no results posted. The published research record is otherwise in vitro and animal work, most of it conducted to determine which part of thymosin beta-4 accounts for a given activity rather than to develop the fragment as a candidate in its own right.
Highest research phase reached
Phase 1/2 registered in 2026 (recruiting, no results posted); otherwise in vitro and animal research only
Approved uses
None
Approval is compound-specific
No

Status as of . This block is rendered from maintained fields, not from prose, so it cannot go stale in one place and stay current in another.

Chemical & Molecular Characteristics

The register record is specific. UNII QHK6Z47GTG in the FDA/NCATS Global Substance Registration System, named TB-500, with CAS registry number 885340-08-9 and a cross-reference to PubChem compound identifier 62707662. The record stores the seven-residue chain LKKTETQ and records the acetyl group separately, as a modification at the leucine in position 1.

The register's calculated mass is the wrong number to quote. That record carries a calculated average mass of 846.98, which is computed from the bare chain and does not include the acetyl group. The correct figure for the acetylated molecule is the PubChem value, 889.0 g/mol, with molecular formula C38H68N10O14. The 42-dalton gap between them is the acetyl. This is a general property of sequence-derived mass calculations in that register and is worth checking on any modified peptide.

Three substances circulate under closely related names. The acetylated heptapeptide recorded here (889.0 g/mol). The free heptapeptide, PubChem compound identifier 10169788, registry number 476014-70-7, roughly 847 g/mol. And the 43-residue protein thymosin β4, CAS 77591-33-4, 4963.4 g/mol. Any of the three may arrive labelled TB-500.

The mass spectrometry result settles it. The differences are large and unambiguous: 42 daltons between the acetylated and free heptapeptides, and roughly 4,074 daltons between either heptapeptide and the protein. The protein also contains one methionine and therefore one sulfur atom, which neither heptapeptide has, so the molecular formula distinguishes them as well. The certificate of analysis supplied with a laboratory order is the record for a given lot.

Frequently Asked Questions

What is the TB-500 17-23 fragment?
A synthetic seven-residue peptide, Ac-Leu-Lys-Lys-Thr-Glu-Thr-Gln-OH, corresponding to residues 17 to 23 of the 43-residue protein thymosin beta-4. It is the substance the FDA/NCATS register carries under the name TB-500, with UNII QHK6Z47GTG and CAS registry number 885340-08-9. In the literature it is usually written LKKTETQ and described as the actin-binding domain or actin-binding motif of the parent protein.
Why do two different substances both get called TB-500?
Because the registers and the supply trade do not agree. The chemical registers define TB-500 as this heptapeptide. Much of the material sold under that name is the full 43-residue protein thymosin beta-4, which has its own registry number, its own International Nonproprietary Name and a mass about 5.6 times larger. The TB-500 entry in this library covers the protein and sets out how to tell the two apart on paper; the shortest test is the mass, 889.0 g/mol against 4963.4 g/mol.
Does the fragment sequester actin?
The biochemical evidence says it should not do so on its own. Mutational mapping of the actin binding site of thymosin beta-4 found two separate structural entities: an N-terminal region spanning residues 1 to 16, which has to adopt an alpha-helix and contacts actin through a hydrophobic patch, and a hexapeptide motif at residues 17 to 22 [2]. Separately, in the DNase I inhibition assay that measures actin sequestration, fragments lacking the N-terminal region did not inhibit polymerisation of G-actin at all [1]. This fragment carries the motif and not the helix.
Then why is it studied at all?
Because several of the parent protein's cell-level activities track the motif rather than the actin sequestration. Using naturally occurring protein, proteolytic fragments and synthetic peptides, the seven-residue motif was found to be essential for angiogenic activity: in endothelial migration assays and in chick aortic arch sprouting assays, the protein and the motif showed near-identical activity at around 50 nM, while peptides lacking any part of the motif were inactive [6]. That is a dissociation between two properties of the same protein, and it is the reason the fragment has a literature of its own.
Is the fragment FDA approved?
No. It has not been approved by the U.S. Food and Drug Administration for any indication.
Has the fragment been studied in humans?
One trial of the fragment as such has been identified: a phase 1/2 study registered in 2026, described in its registry record as concerning the thymosin beta-4 17-23 fragment, with cardiovascular biomarker endpoints and a planned enrolment of 80. It is recruiting and has no results [10]. Every completed human trial in this field used the full-length protein, and those results belong to the thymosin beta-4 record.
What animal evidence exists for the fragment specifically?
One endpoint in one model. In 26-month-old aged mice with full-thickness dermal wounds, the actin-binding domain supplied as the seven-amino-acid synthetic peptide promoted repair comparably to the parent molecule [5]. That is the extent of the in vivo record for the isolated fragment, and it should be read for what it says rather than extended to other tissues, other species or other endpoints.
What identifiers are published for the fragment?
UNII QHK6Z47GTG, CAS registry number 885340-08-9 and PubChem compound identifier 62707662, with molecular formula C38H68N10O14 and an average mass of 889.0 g/mol. One caution: the register's own calculated mass for the record, 846.98, is computed from the bare seven-residue chain and omits the N-terminal acetyl group it separately records as a modification. The unacetylated free heptapeptide is a different substance, with PubChem compound identifier 10169788 and registry number 476014-70-7.

Scientific References

  1. Hannappel E, Wartenberg F. Actin-sequestering ability of thymosin beta 4, thymosin beta 4 fragments, and thymosin beta 4-like peptides as assessed by the DNase I inhibition assay Biological chemistry Hoppe-Seyler; 1993. PMID 8471179
  2. Van Troys M, Dewitte D, Goethals M, et al.. The actin binding site of thymosin beta 4 mapped by mutational analysis The EMBO journal; 1996. PMID 8617195
  3. Malinda KM, Sidhu GS, Mani H, et al.. Thymosin beta4 accelerates wound healing The Journal of investigative dermatology; 1999. PMID 10469335
  4. Huff T, Müller CS, Otto AM, et al.. beta-Thymosins, small acidic peptides with multiple functions The international journal of biochemistry & cell biology; 2001. PMID 11311852 doi:10.1016/s1357-2725(00)00087-x
  5. Philp D, Badamchian M, Scheremeta B, et al.. 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 and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society; 2003. PMID 12581423 doi:10.1046/j.1524-475x.2003.11105.x
  6. Philp D, Huff T, Gho YS, et al.. The actin binding site on thymosin beta4 promotes angiogenesis FASEB journal : official publication of the Federation of American Societies for Experimental Biology; 2003. PMID 14500546 doi:10.1096/fj.03-0121fje
  7. Sosne G, Qiu P, Goldstein AL, et al.. Biological activities of thymosin beta4 defined by active sites in short peptide sequences FASEB journal : official publication of the Federation of American Societies for Experimental Biology; 2010. PMID 20179146 doi:10.1096/fj.09-142307
  8. 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 opinion on biological therapy; 2018. PMID 30063851 doi:10.1080/14712598.2018.1478961
  9. Ying Y, Lin C, Tao N, et al.. Thymosin β4 and Actin: Binding Modes, Biological Functions and Clinical Applications Current protein & peptide science; 2023. PMID 36464872 doi:10.2174/1389203724666221201093500
  10. TB-500 (Thymosin Beta 4 17-23 Fragment) for Cardiovascular Biomarkers in Stable ASCVD 2026. NCT07487363

Every identifier above is resolved against PubMed, Crossref or ClinicalTrials.gov at build time, and the title returned by the register is compared with the title stored here. A page does not publish if a reference fails to resolve.

Research-Use Information

For in vitro research use only. This material is a laboratory reagent. It is not a drug, food, dietary supplement, or cosmetic and is not for human or veterinary use, including ingestion, injection, or any other administration. No information on this page describes or implies any effect in humans or animals. Sold only to researchers under our Terms of Sale.