What it is
Thymosin beta-4 is the endogenous 43-amino-acid protein encoded by the gene TMSB4X, one of a family of beta-thymosins whose core job in the cell is binding monomeric actin. In its natural form it carries an acetylated N-terminal serine, molecular formula C212H350N56O78S, molecular weight 4921 g/mol. Its WHO-recommended international nonproprietary name is timbetasin. FDA’s Global Substance Registration System assigns it UNII 549LM7U24W, and lists its CAS number as 77642-24-1, though chemical-supplier reference standards widely give a different CAS, 77591-33-4; both numbers circulate and neither has been reconciled in the public record.
A related, nearly identical protein, TMSB4Y, sits on the Y chromosome and differs from TMSB4X’s product at only two residues. It is a distinct gene product and is not covered by this entry.
This is not the same molecule as “TB-500,” and that distinction is the reason this entry exists
Material sold online as “TB-500” is not full-length thymosin beta-4. Chemists who analysed marketed TB-500 formulations by HPLC and high-resolution mass spectrometry identified the contents as Ac-LKKTETQ, a synthetic, N-terminally acetylated seven-amino-acid fragment corresponding to residues 17 through 23 of the 43-residue parent protein, about 18 percent of it by length. A racing-laboratory analysis reached the same identification independently, describing the veterinary preparation as containing “the peptide LKKTETQ with artificial acetylation of the N-terminus.”
FDA’s own characterisation of the substance, published in a briefing document dated 15 May 2026 prepared for a Pharmacy Compounding Advisory Committee meeting, gives TB-500 a separate CAS number (885340-08-9), a separate molecular formula (C38H68N10O14), a molecular weight of 889.01 g/mol, and a UNII entirely distinct from thymosin beta-4’s own: QHK6Z47GTG rather than 549LM7U24W. Two different UNII codes is FDA’s registry saying, in the plainest terms a substance database can say it, that these are two different substances.
FDA’s document goes further than simply cataloguing the difference. It states that acetylation of a peptide “irreversibly alters” its charge, hydrophobicity and size, and concludes that the pharmacological profile of the non-acetylated seven-amino-acid fragment cannot be directly extrapolated to the N-acetylated version sold as TB-500. The same logic runs in the other direction: if a seven-residue fragment’s behaviour cannot be assumed from another seven-residue fragment that differs only by one acetyl group, it certainly cannot be assumed from the 43-residue parent protein this entry covers.
The structural literature on the parent protein supports treating the fragment as functionally separate rather than as a smaller dose of the same thing. Work mapping thymosin beta-4’s actin-binding domain found that the LKKTET motif forms the contact site with actin, but that the activity which actually sequesters actin and blocks its polymerisation requires a separate, non-conserved segment upstream of that motif, a segment the seven-residue fragment does not contain. Separately, domain-mapping work in mice and pigs localised thymosin beta-4’s cardiac-repair benefit not to residues 17-23 but to the four residues at the opposite end of the protein, the C-terminal AGES sequence at positions 40-43. Attaching a cardiac claim to TB-500 attaches it to the wrong end of the molecule.
This site maintains a separate entry for TB-500 itself, covering its own chemistry, its own animal and regulatory record, and the grey-market dosing pattern sold under that name; readers who arrived here looking for that material should look there instead. The conflation between the two runs in both directions in real vendor and even peer-reviewed writing: some sellers list the seven-residue fragment as “Thymosin Beta-4 Synthetic Molecule,” others sell material advertised as “TB-500” while describing the contents as “Full-Length 43 AA,” and at least one 2026 review in a peer-reviewed journal invented a nonexistent “thymosin beta-500” as though the product number were a naming convention for a distinct peptide length.
Ac-SDKP is a third, separate molecule
A further fragment sometimes pulled into this same confusion is Ac-SDKP, N-acetyl-seryl-aspartyl-lysyl-proline, INN goralatide. It is the N-terminal four residues of thymosin beta-4, positions 1 through 4, a different and shorter sequence from the seven-residue 17-23 region that is TB-500. Ac-SDKP has its own independent anti-fibrotic literature: in cultured human lung fibroblasts and in a bleomycin mouse model of lung fibrosis, Ac-SDKP inhibited markers of myofibroblast differentiation and, in that model, showed greater anti-fibrotic effect than the intact parent protein, which the study found did not hold back fibrosis by 14 to 21 days despite protecting against it at seven days. At least one retail listing has been observed selling material labelled “TB-500 Thymosin Beta-4 Fragment 1-4,” a name that, if the 1-4 numbering describes the actual contents, identifies Ac-SDKP rather than TB-500 sold under the wrong name. Three molecules, three sequences, one recurring source of confusion.
Mechanism, and where the animal-to-human line actually sits
Beta-thymosins including thymosin beta-4 bind monomeric G-actin in a one-to-one complex, buffering the cell’s free actin pool and holding a reserve of monomer available for rapid cytoskeletal remodelling; the binding affinity for this complex has been characterised at roughly one micromolar in cell-free biochemical systems. A widely cited active-site map assigns the N-terminal Ac-SDKP region to anti-inflammatory and anti-fibrotic activity, and the LKKTETQ region within the intact protein to promotion of angiogenesis, cell migration and wound healing; because this map is so often quoted in support of TB-500 specifically, it is worth restating that it describes activity of the intact protein and of the non-acetylated fragment, not of the acetylated product sold as TB-500.
In cultured cardiomyocytes and in mice after coronary artery ligation, thymosin beta-4 formed a complex with the proteins PINCH and integrin-linked kinase, activating Akt signalling associated with improved early myocyte survival and cardiac function; domain-mapping work, described above, localised this specific benefit to the C-terminal AGES tetrapeptide rather than to the 17-23 region. In a human biomarker sub-study nested inside an unrelated stem-cell trial for chronic ischaemic heart failure, in which no thymosin beta-4 was administered at all, plasma thymosin beta-4 rose significantly 24 hours after intracardiac stem-cell injection, and that rise correlated with improvement in heart-failure functional class. That finding shows endogenous thymosin beta-4 mobilisation tracking with cardiac repair in humans; it is not evidence that giving the peptide produces the same effect, because no one in that study received it.
Every specific molecular mechanism attributed to thymosin beta-4, from G-actin sequestration kinetics through the PINCH/integrin-linked-kinase/Akt cardiac pathway to the anti-fibrotic activity of Ac-SDKP, has been characterised in cell culture and in rodent (and in the cardiac work, porcine) models. No human study located directly measured thymosin beta-4’s actin-sequestering activity, cardiac progenitor mobilisation or angiogenic signalling as a pharmacodynamic endpoint; the human trials described below measured downstream tissue outcomes such as corneal staining and wound closure, not the molecular mechanism itself. One further mechanism is worth naming for balance rather than benefit: peptides spanning thymosin beta-4’s 17-23 region, tested in murine and human mast cells, triggered histamine and tryptase release at a level equal to or higher than the intact protein, a mediator-release pathway rather than a repair pathway, and one that receives far less attention than the repair claims built on the same region.
What the human trials of full-length thymosin beta-4 actually found
RegeneRx Biopharmaceuticals and its ophthalmic joint venture ReGenTree have run a genuine, multi-decade clinical development program on full-length thymosin beta-4 under the development codes RGN-352 (intravenous), RGN-259 (ophthalmic, 0.1% solution) and RGN-137 (topical gel), and a separate Chinese developer, Beijing Northland Biotech, has run its own recombinant human thymosin beta-4 program under the code NL005. None of these programs has reached approval.
RGN-352’s Phase 1 trial gave 40 healthy volunteers intravenous thymosin beta-4 as a single dose and then daily for 14 days, across four absolute dose levels from 42 to 1260 milligrams; adverse events were infrequent and mild to moderate, with no dose-limiting toxicity and dose-proportional pharmacokinetics. A planned Phase 2 trial in acute myocardial infarction was placed on an FDA clinical hold in 2011 over a contract manufacturer’s manufacturing-compliance issue, a hold that was never resolved in the public record, and the registered Phase 2 STEMI study is recorded as withdrawn with zero enrollment. RGN-352 has never completed a Phase 2 trial.
RGN-259’s ophthalmic program tested a 0.1% thymosin beta-4 solution in dry eye disease. In a small Phase 2 trial of nine patients with severe or graft-versus-host-disease-associated dry eye, ocular discomfort fell 35.1 percent and total corneal fluorescein staining fell 59.1 percent relative to vehicle at day 56. In a larger, 72-patient Phase 2 trial using a controlled adverse environment model, both co-primary endpoints were missed, though several secondary measures reached significance. The program went on to run three Phase 3 dry-eye trials under the name ARISE, enrolling 317, 601 and 700 patients respectively; the third and largest, per the sponsor’s own 2021 release, did not meet its primary outcome measures, although one pre-specified secondary measure, ocular grittiness, was significant at several timepoints. A separate RGN-259 program for neurotrophic keratopathy has one Phase 3 trial terminated after enrolling only 18 of a larger planned cohort, and a second still recruiting.
Beijing Northland’s NL005 program tested recombinant human thymosin beta-4 by intravenous dose in healthy Chinese volunteers, first as a single ascending dose (54 participants, 0.05 to 25 micrograms per kilogram) and then as repeat daily dosing over 10 days (30 participants, 0.5 to 5.0 micrograms per kilogram per day). Both trials reported the compound well tolerated, with no dose-limiting toxicity and no evidence of drug accumulation with repeat dosing. That same developer has gone on to run completed Phase 2a and 2b trials in acute myocardial infarction, with a Phase 2c trial not yet recruiting as of this writing; no peer-reviewed publication of the Phase 2 results was located.
A blunt fact belongs beside all of this: no human study of any kind has ever administered TB-500, the acetylated seven-residue fragment, to a person. FDA states this directly in its briefing document, and an independent literature search for the term returned no human interventional trial. The one registry record that appears under the name “TB-500” states in its own summary that it is a fictional example record and must not be read as evidence of a trial. Every milligram figure that has ever been measured in a human being for this molecular family was measured for full-length thymosin beta-4 or its recombinant equivalent, using intravenous or ophthalmic routes in a monitored clinical setting, not for the fragment sold online, and not by self-administered subcutaneous injection.
Safety
Across the trials above, adverse events for full-length thymosin beta-4 and its recombinant equivalent were consistently described as infrequent and mild to moderate, with no dose-limiting toxicity reported in either the RegeneRx intravenous Phase 1 (40 participants) or the Beijing Northland NL005 Phase 1a/1b program (54 and 30 participants). The ARISE-3 dry-eye trial (700 participants) reported no serious adverse events, with mild ocular pain on instillation as the most common event, at 6.6 percent on active treatment against 4.6 percent on placebo.
What is not established is longer-term safety. The longest published intravenous dosing period for full-length thymosin beta-4 located in the record is 14 days. No comparative long-term, multi-year safety cohort for the peptide has been completed and published; a company claim of exposure across roughly 1,700 patients is a corporate statement rather than a peer-reviewed finding and should not be treated as an established safety record. Immunogenicity assessment for full-length thymosin beta-4 specifically was not located in any of the trials reviewed here, an open question FDA raises far more pointedly about the injectable TB-500 fragment, for which it states that no clinical immunogenicity studies exist at all.
Regulatory status
Full-length thymosin beta-4 is not FDA-approved for any indication in any population; no source located establishes an approval anywhere for the peptide. It does not appear on any FDA bulk drug substances list reviewed in this research pass. Its entire US regulatory footprint is the IND-stage clinical development described above, run by RegeneRx, ReGenTree and Beijing Northland, none of which has yet reached a marketing application.
The World Anti-Doping Agency’s Prohibited List names “Thymosin-β4 and its derivatives e.g. TB-500” under section S2.3, Growth Factors and Growth Factor Modulators, a non-specified category prohibited at all times, in and out of competition. By naming the parent molecule and explicitly extending the prohibition to its derivatives, WADA’s drafting sidesteps the identity question this entry exists to explain: the fragment is caught by the rule whether or not it is chemically identical to the protein it is named after.
TB-500 itself, evaluated by FDA under its own name and its own chemical identity, appears on FDA’s list of bulk drug substances nominated for compounding but withdrawn, with an explicit note that compounded drugs containing it may pose a risk for immunogenicity. FDA’s 15 May 2026 briefing document proposed not adding TB-500 to the compounding list at all, citing inadequate physicochemical characterisation, no history of compounding use, no evidence of effectiveness and unknown human safety risk. That evaluation, and TB-500’s separate warning-letter and horse-racing record, belong to this site’s TB-500 entry rather than to the molecule covered here, but the fact that regulators evaluate the two under entirely separate identities, with separate UNII codes and a separate CAS number, is itself part of the evidence that they are not the same substance.
What circulates, and what it is being measured against
Because “TB-500” is the name people actually search, and because it is what is bought, injected and cycled under a name that borrows this protein’s identity, an honest thymosin beta-4 entry has to show what that market looks like rather than pretend it does not exist. The pattern below is read off the general, aggregate shape of research-peptide vendor material, not independently re-verified this session; no vendor is named, no figure is dated, and none of it should be read as a protocol.
Circulating TB-500 material is described almost universally as self-administered by subcutaneous injection, with a “loading” phase commonly clustering around 2 to 2.5 milligrams given twice weekly (roughly 4 to 5 milligrams per week) for four to six weeks, followed by a “maintenance” phase around 2 to 2.5 milligrams per week, with total cycle lengths commonly described as 8 to 12 weeks. It is frequently sold blended with BPC-157 as the “Wolverine blend,” and as one of four components in “KLOW.”
None of that pattern maps onto anything actually studied in a human being. The two real intravenous thymosin beta-4 programs used absolute and weight-based dosing that differ from each other by roughly four orders of magnitude — RegeneRx’s Phase 1 gave 42 to 1260 milligrams per dose intravenously in a monitored clinical unit, while Beijing Northland’s NL005 program gave 0.05 to 25 micrograms per kilogram, roughly 3.5 micrograms to 1.75 milligrams for a 70-kilogram adult, also intravenously and also monitored. The milligram-scale numbers that circulate for TB-500 sit inside the RegeneRx trial’s absolute mass range, which is very likely why a milligram-scale, self-administered subcutaneous dose feels precedented to someone who has come across that trial — but the molecule is different (43 amino acids and 4921 daltons against 7 amino acids and 889 daltons), the route is different (monitored intravenous infusion against unsupervised subcutaneous injection), and, per the point made above, no dose of TB-500 itself has ever been given to a human being in any published study at all. Per this site’s policy on established dosing, the only accurate statement for TB-500 is that no dose has been established, not an extrapolation from a different molecule’s intravenous trial.
What the record gets wrong, and why it matters
The single most consequential error circulating about this molecule is the assumption that “TB-500” is simply a shorthand or a more potent version of thymosin beta-4 itself. It is not a dosing-strength distinction; it is a different molecule, independently characterised by mass spectrometry, carrying its own separate FDA substance identifier, evaluated by FDA under its own name, and explicitly excluded by FDA from having its pharmacology inferred from either the intact protein or the non-acetylated version of the same seven residues. A regulator writing that a fragment’s effects “cannot be directly extrapolated” from its own close chemical relative is about as plain a warning against conflation as a chemistry document gets.
The second error is treating thymosin beta-4’s own, real clinical record as more settled than it is. A genuine, decades-long, well-funded development program reached Phase 3 in dry eye disease and missed its primary endpoints in the largest of those trials; a Phase 2 epidermolysis bullosa trial and a Phase 3 keratopathy trial each terminated with only a handful of patients enrolled; and the one injectable program with a positive safety signal stalled behind a manufacturing hold more than a decade ago and was never restarted. This is a molecule with a long, honestly documented, and largely unsuccessful path through human trials, not an established therapy waiting to be rediscovered under a different name. No dose of thymosin beta-4, and certainly none of TB-500, has been established as safe or effective for any use outside a completed clinical trial, and no source reviewed here supports treating either molecule as anything other than an unapproved, investigational or unregulated substance.