TB500

Classification

Synthetic 7-residue fragment of thymosin beta-4 — not the same molecule as Tβ4

Structure and chemistry

TB-500 is the acetylated heptapeptide Ac-Leu-Lys-Lys-Thr-Glu-Thr-Gln (Ac-LKKTETQ), roughly 889 daltons. It corresponds to residues 17 to 23 of thymosin beta-4, the actin-binding motif. Thymosin beta-4 itself is a 43-residue protein of about 4,963 daltons (CAS 77591-33-4) with the sequence Ac-SDKPDMAEIEKFDKSKLKKTETQEKNPLPSKETIEQEKQAGES. These are two different molecules with different masses, different pharmacokinetics and different regulatory histories, and the distinction is the single most important thing to understand about this product.

What the published research shows

Here is the part that matters. Essentially all human clinical trial data attributed to “TB-500” was generated using full-length thymosin beta-4, not the fragment. RegeneRx Biopharmaceuticals ran clinical programs — including Phase 2 work in dry eye disease and studies in wound healing and cardiac repair — using the intact 43-residue protein. No pharmaceutical company has pursued the TB-500 fragment as a drug candidate for any indication, and the fragment itself has no published human clinical trials. Animal wound-healing data exists for both the full protein and short actin-binding fragments.

Mechanism of action

Thymosin beta-4 is the body’s principal G-actin sequestering molecule, present at roughly 300 to 500 micromolar in the cytoplasm of nearly all mammalian non-muscle cells and binding G-actin in a 1:1 ratio, sequestering an estimated 40 to 50 percent of the total G-actin pool. It also promotes angiogenesis through VEGF upregulation, modulates inflammation via NF-kB, and reduces fibrosis by inhibiting TGF-beta-driven collagen deposition. The LKKTETQ fragment reproduces the actin-binding motif, but crystallographic work shows essentially the entire thymosin beta-4 sequence participates in actin interaction, and the full protein carries functional domains the fragment simply does not have.

Development history

Thymosin beta-4 was isolated from bovine thymus in 1981 by Teresa L.K. Low and Allan L. Goldstein — the same NIH-funded thymosin program that produced thymosin alpha-1, also in this catalog. Hynda Kleinman’s group at the National Institute of Dental and Craniofacial Research established much of the core actin and wound-healing biology through the following decade. TB-500 as a distinct commercial fragment emerged later and was first characterized in the analytical literature in 2012.

Current regulatory status

Neither TB-500 nor thymosin beta-4 is FDA-approved for any indication. The thymosin beta-4 fragment (LKKTETQ) was nominated to FDA’s bulk drug substances list for pharmacy compounding; the nomination was withdrawn. A 2024 study reported that TB-500 is rapidly metabolized to Ac-LKKTE, raising the possibility that observed activity comes from the metabolite rather than the parent peptide.

Analytical testing

This is the catalog item where a COA most needs reading carefully. Confirm which molecule you actually have: the 7-residue fragment and the 43-residue protein differ by roughly 4,000 daltons, so mass spectrometry settles it immediately. Check that the reported molecular weight and CAS number correspond to the material being sold rather than to full-length thymosin beta-4. The N-terminal acetylation should also be confirmed, since the free-amine heptapeptide is a different compound.

Ordering from Great Falls

MontanaPep, also known as Montana Peptides, is an independently owned supplier based at 715 13th Ave S, Great Falls, Montana. Local pickup is available by arrangement, and we ship to research addresses across Montana including Billings, Missoula, Bozeman, Helena, Butte, Kalispell and Havre. Call (406) 799-0812 or email customerservice@montanapep.com.

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