Peptides›Healing›Thymosin Beta-4 (TB-4)

Thymosin Beta-4 (TB-4)

/ Endogenous 43-residue actin-sequestering peptide; expressed by gene TMSB4X

TIER 2 · TranslationalN = 0 · TESTING PENDINGMW 4963.40 g·mol⁻¹

ALIAS · Tβ4 · TMSB4 · Full-length thymosin beta-4 · RGN-259 (ophthalmic formulation, RegeneRx)

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Research use onlyAny dose figures below describe what specific cited studies used, reported factually. Nothing on this page is guidance for human use.READ FIRST →

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§ A · Identity

Primary sequenceSDKPDMAEIEKFDKSKLKKTETQEKNPLPSKETIEQEKQAGES

MW · 4963.40CLASS · Endogenous 43-residue actin-sequestering peptide; expressed by gene TMSB4XCATEGORY · Healing

Tier 2. Full-length 43-residue thymosin beta-4 has multiple Phase 2 studies (cardiac, neuro, ophthalmic indications) and a failed Phase 3 in dry-eye disease (RGN-259, ARISE-3, 2018). The parent molecule of vendor-sold TB-500 (which is a synthetic actin-binding fragment marketed as 'thymosin beta-4 fragment').

§ B · Mechanism of action

TB-4 binds monomeric G-actin in a 1:1 complex, sequestering it from polymerisation into F-actin filaments. Beyond actin sequestration, TB-4 has multiple non-canonical activities: binding to PINCH/ILK in the integrin-linked kinase complex, modulating cytokine production, supporting angiogenesis (FGF and VEGF expression), and recruiting endogenous progenitor cells in cardiac and dermal injury models.

§ C · Human clinical evidence

Tier 2. Phase 2 trials in acute myocardial infarction (RegeneRx-sponsored), pressure ulcer healing, and corneal disease produced mixed results. The Phase 3 ARISE-3 trial of RGN-259 ophthalmic in dry-eye disease did not meet primary endpoint (2018); RegeneRx subsequently restructured.

§ D · Primary literature

PubMed16099219Goldstein AL et al. — Thymosin β4: actin-sequestering protein moonlights to repair injured tissues · Trends in Molecular Medicine · reviewFoundational review of TB-4's tissue-repair mechanisms beyond G-actin sequestration: angiogenesis, anti-inflammatory cytokine modulation, stem-cell recruitment in dermal and corneal models.Limitations: Review by inventors of the molecule; written before the failed Phase 3 corneal trial of RGN-259.2005

PubMed15565145Bock-Marquette I et al. — Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair · Nature · rodentTB4 activated integrin-linked kinase, promoted epicardial cell migration, and improved cardiomyocyte survival after myocardial infarction in mice.Limitations: Murine MI model; mechanistic — clinical translation has not been established.2004

PubMed11950239Sosne G et al. — Thymosin beta 4 promotes corneal wound healing and decreases inflammation in vivo following alkali injury · Experimental Eye Research · rodentTopical TB4 accelerated re-epithelialisation and reduced inflammatory infiltrate in a murine alkali-burn corneal wound model.Limitations: Rodent acute-injury model; clinical translation to humans assessed in later trials.2002

PubMed22074294Goldstein AL et al. — Thymosin beta4: a multi-functional regenerative peptide. Basic properties and clinical applications · Expert Opinion on Biological Therapy · reviewReviewed TB4 biology, actin-sequestering function, and the spectrum of preclinical and early-phase clinical applications across cardiac, neural, and corneal repair.Limitations: Narrative review by the molecule's lead investigator; coverage of negative trials limited.2012

§ F · Safety signal

In published Phase 2 data well tolerated by intravenous, subcutaneous, and ophthalmic routes; long-term safety database limited. Class concern about pro-angiogenic effects in patients with active malignancy is theoretical but warrants caution.

§ H · Regulatory status

Regulatory status

FDA status:: Not FDA-approved

§ I · Notable gaps and controversies

Vendor-sold 'TB-500' is a 17-residue synthetic actin-binding fragment of TB-4, not the full-length molecule. Marketing that conflates TB-500 with TB-4 evidence overstates the case — the fragment retains some but not all of the parent's activities.