TB-500 / Thymosin Beta-4

An unapproved fragment of thymosin beta-4

Not FDA-approved · not available for sale or prescription

FDA advisory vote, July 2026 · FDA staff opposed · no FDA action

Stylised model of the real sequence

Overview.

The names TB-500 and thymosin beta-4 cover two related but distinct substances, and neither is an approved drug. 'Thymosin beta-4' (Tβ4) is the natural, N-acetylated 43-amino-acid human protein (UniProt P62328) that sequesters G-actin; it has been tested in human Phase 2 and 3 trials for dry eye, cardiac and dermatologic conditions under the development names RGN-259 and RGN-137, and a Phase 3 dry-eye trial missed its main goals. 'TB-500', as sold by research-peptide vendors and as reviewed by FDA's compounding advisory committee, is a much shorter synthetic 7-amino-acid fragment (Ac-Leu-Lys-Lys-Thr-Glu-Thr-Gln-OH, the actin-binding domain of Tβ4). It is not the same molecule as full-length thymosin beta-4, FDA found no human data for it, and it is the form on FDA's compounding lists and the WADA Prohibited List.

Also known as Thymosin β4 · Tβ4 · TB4 · TB-500

The molecule, decoded.

Sequence: Full-length/mature (43 aa, N-acetylated): Ac-SDKPDMAEIEKFDKSKLKKTETQEKNPLPSKETIEQEKQAGES-OH. Commercial 'TB-500' fragment (7 aa): Ac-LKKTETQ-OH.
Length: 7 residues
Molecular weight: 889 g/mol
Formula: C38H68N10O14 (TB-500, Ac-LKKTETQ-OH); full-length Tβ4: C212H350N56O78S
CAS number: 77591-33-4 (full-length Tβ4); 885340-08-9 (TB-500 fragment)
Half-life: Not established
Routes studied: intravenous (human, AMI trial), topical ophthalmic solution (human, dry-eye trials), subcutaneous (animal), intra-articular injection (human, off-label combination use)
Modifications: Full-length: N-terminal acetylation of Ser1 (initiator Met cleaved from the 44-aa UniProt precursor). Fragment: N-terminal acetylation of Leu, free C-terminal acid.

How it works.

Full-length Tβ4 binds and sequesters monomeric G-actin, regulating cytoskeletal remodeling, cell migration, and angiogenesis; it also has reported anti-inflammatory and anti-apoptotic signaling roles that promote wound and corneal epithelial healing. The 7-mer fragment (Ac-LKKTETQ, marketed as TB-500) contains the actin-binding motif and is proposed to reproduce some cell-migration/angiogenic effects, but has far less direct mechanistic study than the parent protein.

Evidence · Lab and animal studies only

What the research shows

phase 3 RCT2018

In the Phase 3 ARISE-2 trial, RGN-259 eye drops (preservative-free, full-length Tβ4) given for 28 days did not beat placebo on either co-primary endpoint at Day 29 in 601 adults with dry eye: posted changes were +0.07 vs -0.04 for ocular discomfort and +0.07 vs -0.01 for corneal fluorescein staining, with overlapping 95% CIs. Serious adverse events occurred in 3/299 vs 2/302. The trial used full-length Tβ4, not the TB-500 fragment.

601 adults with dry eye syndrome (Phase 3)

Source

phase 2a RCT, no results2021

A Phase 2a trial of intravenous recombinant human thymosin beta-4 (NL005) versus placebo after PCI for acute myocardial infarction finished in November 2021; no results have been posted or published.

62 adults with acute MI after PCI (Phase 2a, Beijing Northland Biotech)

Source

retrospective chart review2021

In a retrospective chart review at one clinic with no control group, 3 of the 4 patients given knee injections of BPC-157 combined with thymosin beta-4 reported improvement, vs 11 of 12 given BPC-157 alone.

4 of 16 total patients received the combination (Orlando, FL)

Source

cell study2024

In lab work on human adipose-derived stem cells, thymosin beta-4 (100-1000 ng/mL) increased cell proliferation and resistance to cell death and upregulated angiogenesis- and Hippo-pathway-related genes, which the authors proposed may explain effects on fat-graft survival.

human adipose-derived stem cells from liposuction donors

Source

What to know first.

Based on: human trials of full-length thymosin beta-4 (RGN-259, RGN-137); only lab and animal studies and anecdotal reports for the TB-500 fragment.

Reported side effects

Full-length Tβ4 eye drops (RGN-259) in the Phase 3 ARISE-2 trial: serious adverse events 3/299 vs 2/302 on placebo and other adverse events 19/299 vs 21/302 (posted results); no results have been posted for the Phase 2a IV cardiac trial (NCT05485818)
FDA found no clinical studies or human exposure data for the TB-500 fragment, so its human safety risks are unknown; one FAERS report described diffuse hyperpigmentation and gingival darkening, recurring on rechallenge, with a 'research purposes only' product combining BPC-157 and TB-500

Cautions

Consumers and clinicians frequently conflate the well-studied full-length protein with the little-studied fragment sold under the same commercial name
Unregulated research-vendor product with no independent check of purity or identity

Checked 2026-09

Where it stands.

Not FDA-approved · not available for sale or prescription. TB-500 / Thymosin Beta-4 is not FDA-approved and is not available for sale or prescription. In July 2026, FDA staff recommended against adding it to the list of substances pharmacies may compound; FDA’s advisory committee voted 8–6, with 1 abstention, to recommend it anyway. The vote is advisory, and FDA has not acted on it.

FDA: Not approved as a drug under either name. Full-length Tβ4 has been tested in humans: RGN-259 eye drops (RegeneRx/ReGenTree) completed Phase 3 dry-eye trials, and ARISE-2 missed both co-primary endpoints; RGN-137 gel completed a Phase 2 venous stasis ulcer trial (NCT00832091); RegeneRx's injectable cardiac trial (RGN-352, NCT01311518) was withdrawn before enrolling anyone; a separate Phase 2a IV trial by Beijing Northland Biotech (NL005, NCT05485818) finished in 2021 with no results posted. The 7-aa fragment sold as 'TB-500' (Ac-LKKTETQ; FDA found no human data) was reviewed at the PCAC on 23 Jul 2026 for wound healing: FDA proposed NOT adding TB-500 free base or acetate, and the committee voted 8 yes, 6 no, 1 abstain on each form to recommend inclusion (non-binding). No proposed or final rule as of 26 Sep 2026.
Compounding: Nominated for the 503A Bulks List by Wells Pharmacy Network as 'Thymosin Beta-4, Fragment (LKKTETQ) of TB500' (received 29 Aug 2022, FDA-2015-N-3534-0304). It was held in 503A Category 2; Wells withdrew on 14 Apr 2026 (FDA-2015-N-3534-0484), and FDA's Category 2 page (updated 22 Apr 2026) now lists 'Thymosin beta-4, fragment (LKKTETQ), also known as TB-500' under 'nominated but withdrawn'. LDT Health Solutions separately withdrew a 'Thymosin B4' nomination on 20 Apr 2026. FDA evaluated TB-500 free base and acetate on its own initiative and proposed NOT adding them; on 23 Jul 2026 the PCAC voted 8-6-1 on each form to recommend inclusion (non-binding). As of 26 Sep 2026 FDA has published no proposed or final rule: the substance is not on the 503A bulks list (21 CFR 216.23, unchanged since 2019) and is not in 503A Category 1.
Sport (WADA): Thymosin-β4 and its derivatives, explicitly naming 'TB-500', are prohibited at all times under S2.3 (Growth Factors and Growth Factor Modulators) of the WADA 2026 Prohibited List ('Thymosin-β4 and its derivatives e.g. TB-500').

References (6)

TB-500 / Thymosin Beta-4

Overview.

The molecule, decoded.

How it works.

What the research shows

What to know first.

Reported side effects

Cautions

Where it stands.

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