TB-500

TB-500 (CAS 77591-33-4) is a synthetic heptapeptide with sequence LKKTETQ (Leu-Lys-Lys-Thr-Glu-Thr-Gln), corresponding to residues 17-23 of human Thymosin β-4 (Tβ4), a small 43-amino-acid protein (4960 Da) highly conserved in the animal kingdom. While native Tβ4 plays a pivotal role as G-actin sequestering agent in the cytoskeleton, the isolated LKKTETQ fragment retains significant bioactivity on cell migration, angiogenesis and matrix remodelling.

Molecular mechanisms. TB-500 is studied for its capacity to modulate actin polymerisation via the actin-binding motif identified by Huff et al. (2004), activate ILK/PINCH/parvin and NF-κB pathways, induce miR-146a (anti-inflammatory) and miR-124 (neuroprotection), and stimulate VEGF-A and bFGF release by endothelial cells. Full-length Tβ4 (and by extension its fragments) has also been described to generate Ac-SDKP (acetyl-Serine-Aspartate-Lysine-Proline), an anti-fibrotic and pro-regenerative tetrapeptide via TGF-β1/SMAD inhibition.

Preclinical models. Referenced publications (Bock-Marquette 2004 Nature on infarcted myocardium, MCAO ischaemic stroke studies, mdx Duchenne muscular dystrophy model, bleomycin pulmonary fibrosis, dermal and corneal healing) have explored TB-500 and full Tβ4 use in cardiac, neurological, ocular and musculoskeletal regeneration research. The molecule has also undergone phase II clinical trials in ophthalmology (dry eye syndrome, neurotrophic keratopathy) under the name RGN-259 (RegeneRx Biopharmaceuticals).

Regulatory status. TB-500 is classified RUO (Research Use Only) — no marketing authorisation in Europe or the United States for human use outside clinical protocols. It is also listed on the WADA Prohibited List (World Anti-Doping Agency, section S2.5) for sports competition. Lab Peptides France offers it as lyophilisate in 5mg or 10mg multi-dose vial; the certificate of analysis is published on the 10mg page.