TB-500 (Thymosin β4 fragment, LKKTETQ)

TB-500 is a synthetic seven-amino-acid peptide fragment (Leu-Lys-Lys-Thr-Glu-Thr-Gln; positions 17–23) of the full-length thymosin β4 protein (tmsb4x, 43 aa). It regulates G-actin sequestration, cell migration, and angiogenesis through binding to unpolymerized actin monomers. All published efficacy evidence derives from in vitro or animal models; no peer-reviewed human clinical trials of the LKKTETQ fragment have been reported as of 2026-05-09. Before the FDA’s 2023 action removing it from 503A bulk drug substance lists, it was widely prescribed off-label in regenerative-medicine telehealth settings, typically alongside bpc-157, for musculoskeletal injuries.

Fragment vs full protein — critical distinction

This is the most important precision point on this page. The marketing name “TB-500” is applied inconsistently in product labelling, literature, and clinical reports.

Three related but distinct entities circulate under the “TB-500” umbrella:

Entity	Sequence	Length	Status
Full thymosin β4 (Tβ4)	Full 43-aa sequence	43 aa	Well-studied; endogenous protein; some human evidence for wound indications
Ac-LKKTETQ	N-terminally acetylated 17–23 fragment	7 aa	Most common synthetic form; detected by mass spec in marketed TB-500 products ¹
LKKTETQ (unacetylated)	Unmodified 17–23 fragment	7 aa	PubChem CID 10169788; present in some products; less studied than Ac-form

Esposito et al. (2012), who characterised a commercial TB-500 vial seized by Belgian Customs during a routine control, found it contained the acetylated N-terminal fragment Ac-LKKTETQ (theoretical MW 888.49 Da; measured 888.49 Da by HRMS), not the full Tβ4 or the unacetylated LKKTETQ ¹. The N-terminal acetyl group is present on the native Tβ4 protein as well. Note: this study characterised a single product; product composition may vary across vendors.

Consequence for literature interpretation: The overwhelming majority of published basic-science data on “thymosin β4” pertains to the full 43-aa protein. Claims derived from full-Tβ4 studies (e.g., Philp et al. 2004 ²) should not be directly attributed to the LKKTETQ fragment without explicit confirmation that the fragment was used.

The actin-binding WH2 domain of Tβ4 maps precisely to residues 17–23 (LKKTETQ), so the fragment does retain the canonical actin-sequestration function of the parent protein. However, Tβ4 also exerts effects through other domains (e.g., the Ac-SDKP N-terminal tetrapeptide is immunomodulatory and acts on ACE; the C-terminal domain contributes to nuclear localisation) — these activities are absent from the fragment.

Metabolite complexity: A 2024 PK study found that TB-500 (Ac-LKKTETQ) is metabolised in biological systems; a key metabolite identified was Ac-LKKTE, which reportedly showed wound-healing activity in NIH 3T3 fibroblast scratch assays while the parent fragment was less active ³. This introduces an additional layer of uncertainty: the observed biological activities of TB-500 may be mediated by metabolites rather than the administered peptide. Note: Rahaman 2024 is closed-access and was not verified against the full PDF — these claims are as reported by the seeder and should be treated as unconfirmed. no-fulltext-access

Identity and canonical IDs

PubChem CID: 10169788 (LKKTETQ unacetylated form; confirmed via PubChem REST API)
Molecular formula: C36H66N10O13 (unacetylated LKKTETQ; confirmed via PubChem)
Molecular weight: 847.0 Da (unacetylated LKKTETQ; confirmed via PubChem); Ac-LKKTETQ MW = 888.49 Da (measured 888.4910 by Esposito 2012 HRMS ¹)
ChEMBL ID: null — not indexed; needs-canonical-id
DrugBank ID: null — not indexed; needs-canonical-id
WHO INN: none assigned
Sequence: Leu-Lys-Lys-Thr-Glu-Thr-Gln (one-letter: LKKTETQ)
Positions in parent protein: aa 17–23 of tmsb4x (human thymosin β4; UniProt P62328)
CAS (Ac-LKKTETQ): Not confirmed in archive — needs-canonical-id
WADA status: Prohibited in sport under S2 (Peptide Hormones, Growth Factors, and Related Substances); full Tβ4 and fragments are both prohibited. Esposito 2012 developed analytical detection methods to enable anti-doping enforcement against this substance ¹
FDA regulatory status: Removed from 503A bulk drug substance list (2023); compounding of TB-500 for human use by 503A pharmacies is no longer permitted in the US

Mechanism of action

Canonical: G-actin sequestration

Thymosin β4 and its 17–23 fragment bind globular (G) actin monomers with high affinity (~0.5 µM Kd for full Tβ4), sequestering them from incorporation into filamentous (F) actin ⁴. This shifts the G-actin/F-actin equilibrium and modulates:

Cell migration — reduces lamellipodia formation via altered actin pool dynamics; counterintuitively, Tβ4-treated cells show increased migration in many wound assay contexts, attributed to complex reorganisation of actin nucleation complexes
Angiogenesis — endothelial cell migration requires dynamic actin remodelling; Tβ4 promotes angiogenic sprouting in corneal and wound models in rodents (full-protein data) ²
Wound healing — keratinocyte and fibroblast migration accelerated in vitro and in rodent excisional wound models (full-protein data) ²

The LKKTETQ fragment contains the WH2 (WASP Homology 2) domain core motif, which is sufficient for G-actin binding. This is mechanistically validated.

Anti-inflammatory activity

Full Tβ4 protein inhibits NF-κB signaling, reduces expression of IL-6, IL-8, and TNFα, and promotes M2 macrophage polarisation in rodent wound models. Whether the LKKTETQ fragment alone drives these effects is not established — much of the anti-inflammatory activity of Tβ4 is attributed to the Ac-SDKP N-terminal tetrapeptide (generated by ACE cleavage), which is absent from the 17–23 fragment. The inclusion of anti-inflammatory in mechanisms: above is extrapolated from full-protein data and should be treated as uncertain for the fragment specifically. no-mechanism

Actin-independent effects

Some wound-healing and neuroprotective effects of Tβ4-derived peptides appear to occur independently of actin binding ⁵, mediated instead through RACK-1 upregulation and downstream PI3K/Akt signalling. Whether LKKTETQ specifically drives these effects is not established.

Pharmacokinetics

No published human PK data for the LKKTETQ fragment. Rat PK from the Rahaman 2024 metabolite study:

Route of administration used in practice: subcutaneous injection (compounded)
Typical marketing dose: 2–5 mg 2–3× per week (no clinical basis)
Primary metabolite in rat serum/urine: Ac-LK (short-term), Ac-LKK (long-term) ³ — unverified; Rahaman 2024 is closed-access no-fulltext-access
Wound-healing-active metabolite: Ac-LKKTE ³ — the clinically relevant species may be metabolic rather than the parent compound — unverified; Rahaman 2024 is closed-access no-fulltext-access

dose-response-unclear — No human dose-response data exists. Rat exposure data is insufficient to establish human-equivalent dosing. The metabolite question (Ac-LKKTE as active species) further complicates any dose extrapolation.

Evidence in aging-relevant contexts

Wound healing and tissue repair

Study	Organism	Form used	Key finding	Quality
Philp et al. 2004 ²	Mouse	Full Tβ4 protein	Accelerated excisional wound closure, increased angiogenesis, hair follicle development	In vivo; full protein, NOT the fragment
Rahaman et al. 2024 ³	In vitro (fibroblasts) + rat urine	Ac-LKKTETQ and metabolites	Ac-LKKTE metabolite reportedly shows wound-healing activity in scratch assay; parent fragment reportedly less active	In vitro + PK; closest direct evidence for marketed form; closed-access — not verified against full PDF no-fulltext-access

Key interpretation note: Philp 2004 is widely cited in TB-500 marketing as evidence of wound-healing efficacy, but it used full thymosin β4 (confirmed by Esposito 2012 ¹ which references Philp et al. for Ac-Tβ4(17-23) biological activities). The only study using the specific commercial fragment form (Ac-LKKTETQ) reportedly found that wound-healing activity resided primarily in a metabolite (Ac-LKKTE) rather than the parent peptide ³ — this claim is unverified (closed-access). needs-replication no-fulltext-access

Neuroprotection / Alzheimer’s disease (adjacent evidence)

Ou et al. (2025) tested Tβ4-derived peptides (including a fragment described as “TB500”) in 5×FAD Alzheimer’s mouse model and reported reduced neuroinflammation and improved neurite density, though hippocampal amyloid burden was unchanged ⁶. The exact fragment form tested was unclear from the abstract. This is highly preliminary.

Musculoskeletal and sports medicine

Mendias and Awan (2026) reviewed peptide therapies for musculoskeletal injuries and concluded that TB-500 “demonstrate[s] favorable tissue repair outcomes in animal models, but rigorous human safety data are scarce” ⁷. Mayfield et al. (2026) similarly reported that both full TB-4 and TB-500 “promoted angiogenesis and tissue repair in preclinical models, but human orthopaedic data are lacking” ⁸. No peer-reviewed randomised controlled trials in humans were identified.

Dimension	Status
Pathway conserved in humans?	yes (G-actin sequestration mechanism is conserved)
Phenotype conserved in humans?	unknown (wound-healing acceleration from rodent data only)
Replicated in humans?	no

Human evidence and clinical trials

As of 2026-05-09: zero completed peer-reviewed human clinical trials of the LKKTETQ fragment. The sole active registered trial is:

NCT07487363 — “TB-500 (Thymosin Beta 4 17-23 Fragment) for Cardiovascular Biomarkers in Stable ASCVD” — Phase 1/2, randomised, double-blind, placebo-controlled; n=80 estimated; sponsor: Hudson Biotech; location: Peking University Shenzhen Hospital, China; status: RECRUITING as of 2026-05-09.

This trial represents the first registered human study specifically of the fragment for any indication. Primary endpoints focused on cardiovascular biomarkers, not aging hallmarks directly.

needs-human-replication — All wound-healing, angiogenesis, and anti-inflammatory claims derive from rodent models using full Tβ4 protein. Fragment-specific data are limited to one in vitro/PK study.

Regulatory and safety context

WADA prohibited: Yes — S2 (both full Tβ4 and fragments). Esposito 2012 developed and validated SRM detection methods for Ac-LKKTETQ in human plasma and urine (spiked at 500 pg/mL) to support anti-doping enforcement ¹
FDA 503A status: Removed from bulk substance list (2023 PCAC review). Pre-ban use in US compounding pharmacies was primarily as subcutaneous injection for musculoskeletal injury, often co-prescribed with bpc-157
Long-term safety: Unknown. No long-term human safety data. Oncological risk from angiogenesis promotion is a theoretical concern — peptide promotes tumour angiogenesis in model systems (parallel concern exists for full Tβ4 in cancer contexts) ⁵
Co-administration with BPC-157: Common in regenerative-medicine telehealth; no interaction studies exist; mechanistically distinct (BPC-157 acts via growth hormone receptor axis; TB-500 via actin). long-term-unknown

Gaps and limitations

#gap/needs-canonical-id — ChEMBL and DrugBank IDs not found for LKKTETQ or Ac-LKKTETQ; CAS not confirmed
#gap/needs-human-replication — all efficacy data from rodents using full Tβ4; one in vitro fragment study (Rahaman 2024, closed-access, unverified) reportedly suggests metabolite (Ac-LKKTE) rather than parent is the active species
#gap/no-fulltext-access — Rahaman 2024 (primary source for Ac-LKKTE metabolite-activity claim) is closed-access with no PMC/OA version; Philp 2004 and Yoon 2021 are also closed-access; Yu 1993 could not be downloaded
#gap/no-mechanism — Anti-inflammatory and neuroprotective effects attributed to TB-500 in marketing are almost certainly derived from full-Tβ4 studies; the fragment-specific mechanism for these effects is unestablished
#gap/dose-response-unclear — No human PK/PD; typical practitioner doses (2–5 mg subcut) have no clinical basis
#gap/long-term-unknown — No chronic safety data; oncological risk from angiogenesis promotion not evaluated
Parent protein page missing: tmsb4x (full thymosin β4, UniProt P62328) does not yet exist in this wiki. It is the canonical protein from which TB-500 is derived and carries the bulk of the mechanistic literature. Recommend seeding as the priority follow-up for this entity cluster.
Literature conflation: The majority of review papers (including the 2026 sports-medicine reviews) treat Tβ4 and TB-500 as interchangeable or cite full-protein studies as evidence for the fragment. This is a pervasive literature-quality problem; claims should be traced to the specific form used before being accepted as fragment evidence.

Cross-references

tmsb4x — parent protein (TMSB4X / thymosin β4; stub needed)
bpc-157 — frequently co-prescribed; stub
peptide-therapeutics — class navigator (stub)
altered-intercellular-communication — plausible hallmark link for paracrine actin-regulatory signalling; not yet established for the fragment
intervention-classes § actin-regulatory-peptide — mechanism class entry

Footnotes

doi:10.1002/dta.1402 · Esposito S, Deventer K, Goeman J, Van der Eycken J, Van Eenoo P · Drug Testing and Analysis 2012 · analytical characterisation (LC-MS/MS + NMR + Fmoc-SPS synthesis) · model: single commercial TB-500 vial (~10 mg, seized by Belgian Customs) characterised by HPLC-HRMS (Exactive Orbitrap) + NMR; confirmed Ac-LKKTETQ (N-terminally acetylated 17-23 fragment, theoretical MW 888.4911 Da) as the entity in the tested TB-500 product; synthesis of Ac-Tβ4(17-23) reference standard performed and confirmed by identical MS/MS and NMR spectra; SRM detection method for plasma and urine developed (LOD: 0.5 ng spiked); WADA anti-doping context discussed · archive: PDF downloaded (OA via Ghent University repository) ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶
doi:10.1016/j.mad.2003.11.005 · Philp D, Goldstein AL, Kleinman HK · Mechanisms of Ageing and Development 2004 · in vivo · model: rodent excisional wound + corneal angiogenesis models; full 43-aa thymosin β4 protein used — NOT the LKKTETQ fragment; reported accelerated wound closure, angiogenesis, hair follicle development; 119 citations · archive: confirmed (doi:10.1016/j.mad.2003.11.005; closed access; not_oa) ↩ ↩² ↩³ ↩⁴
doi:10.1016/j.jchromb.2024.124033 · Rahaman KA, Muresan AR, Min H, Son J, Han HS, Kang MJ, Kwon OS · Journal of Chromatography B 2024 · in vitro + in vivo (rat urine) + fibroblast scratch assay · model: Ac-LKKTETQ incubated in biological matrices; metabolite identification by UHPLC-Q-Exactive Orbitrap MS/MS; wound healing activity of TB-500 and metabolites in NIH 3T3 fibroblast scratch assay; seeder-reported finding: Ac-LKKTE metabolite showed wound healing activity vs parent fragment · archive: closed-access (not_oa); not on PMC or Europe PMC OA · no-fulltext-access — metabolite-activity claims could not be verified against full PDF ↩ ↩² ↩³ ↩⁴ ↩⁵
doi:10.1016/s0021-9258(18)54179-x · Yu FX, Lin SC, Morrison-Bogorad M, Atkinson MA, Yin HL · Journal of Biological Chemistry 1993 · in vitro · model: purified thymosin β4 and β10 proteins; actin sedimentation assay; full 43-aa thymosin β4 protein used; demonstrated G-actin sequestration mechanism · archive: not_oa (no OA URL found); author list verified via Crossref no-fulltext-access ↩
doi:10.1007/s13258-021-01127-7 · Yoon HJ, et al. · Genes and Genomics 2021 · in vitro · model: ovarian cancer cell lines; full Tβ4 and three derived peptide fragments; all fragments stimulated migration/invasion via RACK-1 regardless of actin-binding site presence; suggests actin-independent oncogenic signalling downstream of Tβ4 fragments · archive: not checked ↩ ↩²
doi:10.1016/j.intimp.2025.116097 · Ou H, et al. · International Immunopharmacology 2025 · in vitro + in vivo · model: 5×FAD Alzheimer’s mouse model; Tβ4-derived peptides (including fragment described as TB500); neuroprotective effects on neurite density and neuroinflammation; hippocampal amyloid burden unchanged; fragment form uncertain from abstract · archive: confirmed (doi confirmed; closed access; not_oa) · needs-replication ↩
doi:10.1007/s40279-026-02437-0 · Mendias CL, Awan TM · Sports Medicine 2026 · systematic review/narrative review · no primary data; review of unapproved peptide therapies for musculoskeletal injuries; TB-500 treated as distinct from full Tβ4; conclusion: animal model evidence favorable, human safety data scarce · archive: DOI not found in archive as of 2026-05-09 ↩
doi:10.1177/03635465251357593 · Mayfield CK, Bolia IK, Feingold CL, et al. · The American Journal of Sports Medicine 2026 · narrative review · no primary data; TB-500 and TB-4 discussed as separate entities; both found to promote angiogenesis and tissue repair in preclinical models only; human orthopaedic data described as lacking · archive: confirmed (doi confirmed; closed access; not_oa) ↩

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