Thymic peptides: one gland, three very different things

Thymosin fraction 5

Review A history written by a member of the group says the work began in the early 1960s, and that a 1966 paper gave the thymus-derived factors the name “thymosins”.⁵ During the 1970s the group prepared and tested thymosin fraction 5, a partly purified calf thymus preparation that could be made at scale.⁵ In 1974 it became the first thymic hormone preparation cleared by the FDA for a clinical study, a phase 1 study in children with primary immunodeficiency.⁵ Fraction 5 was a family of at least 40 mostly small, acidic polypeptides with molecular weights from 1,000 to 15,000 daltons.⁵

Review Single peptides were then isolated from the mixture, and a naming scheme for them was proposed in 1977.¹² A 2007 review concluded that none of the isolated peptides were really thymic hormones, though all were biologically important.² One of them, polypeptide beta-1, turned out to be ubiquitin with two residues missing.²

Thymosin alpha-1

Chemistry study Thymosin alpha-1 was sequenced in 1977 from calf thymus as a heat-stable, highly acidic peptide of 28 residues.¹ The chemically produced form is named thymalfasin and has the same sequence; the first residue carries an acetyl group.¹⁴¹⁹

Cell study In 1984 its sequence was found at the start of a larger protein of about 112 residues, named prothymosin alpha.⁶ In rat thymus extracts that protein was the main form detected and the 28-residue peptide was not found, so the authors suggested the peptide arose during the preparation of fraction 5.⁶

Cell study A 2003 study reported that legumain, an enzyme of the lysosome, cuts prothymosin alpha to release thymosin alpha-1, and that the peptide is naturally present in diverse mammalian tissues.⁷

Animal study A 2004 study reported that thymosin alpha-1 made dendritic cells, a type of immune cell, mature through Toll-like receptor signalling.²⁰ In the same study the synthetic peptide protected mice that had received blood stem cell transplants from the fungal infection aspergillosis.²⁰

Thymosin beta-4

Cell study Thymosin beta-4 was sequenced in 1981 as a 43-residue polypeptide from calf thymus, and was described then as a thymic hormone acting on developing T cells.¹³ Ten years later, a peptide that keeps actin in its unassembled form in human platelets proved to have the same sequence and to bind actin one-to-one.⁸

Review A 2007 review describes beta-thymosins as the main actin-sequestering peptides inside most vertebrate cells, and says very little is known about how the effects attributed to them outside cells come about.² The FDA uses the name TB-500 for a seven-residue fragment of thymosin beta-4, and the TB-500 overview sets out which studies belong to which molecule.²¹

Thymalin

Chemistry study A 1997 paper by Morozov and Khavinson describes thymalin as a pharmaceutical containing natural peptides isolated from calf thymus by mild acid extraction.³ From it one dipeptide, glutamic acid-tryptophan, was separated by HPLC, and a synthetic product, Thymogen, was built on that dipeptide.³

Cell study A 2023 paper from the same institute calls thymalin a polypeptide extract of thymus and names two dipeptides as its active substances.⁴ In blood cells from four donors, stimulated in culture, thymalin and both dipeptides lowered the levels of three inflammatory signalling proteins.⁴

A mixture has no single sequence, formula or molecular weight to check a sample against; the guide to analytical methods for peptides explains how such checks work for a defined peptide. The name is also ambiguous: PubChem lists “Thymalin” as a synonym of nonathymulin, a nine-residue peptide and not an extract.²²

Human evidence

• Human study Thymosin alpha-1 in sepsis. A double-blind phase 3 trial at 22 centres in China randomized 1,106 adults to thymosin alpha-1 or placebo, with support declared from the company whose product is Zadaxin.⁹¹⁹ Death from any cause within 28 days occurred in 23.4% and 24.1%, and the authors found no clear evidence of lower mortality.⁹
• Review Thymosin alpha-1 in hepatitis B. A 2026 Cochrane review pooled 10 randomized trials with 1,349 participants.¹⁶ Pooled estimates leaned towards fewer deaths and adverse events with thymosin alpha-1, but the reviewers rated the certainty low for serious adverse events and very low for every other outcome, and wrote that they were not sure whether it reduces mortality.¹⁶
• Thymosin alpha-1, FDA review. FDA staff who assessed 12 proposed uses in 2024 found a lack of evidence of effectiveness and a possible risk of unwanted immune responses, and noted that most clinical studies had not linked the peptide to significant adverse events.¹⁹
• Human study Thymosin beta-4. In a placebo-controlled phase 2 trial of an eye solution in 72 people with dry eye, neither primary endpoint differed from placebo, while some secondary measures did.¹⁷ ClinicalTrials.gov lists other studies of thymosin beta-4 that are not reviewed here.²³
• Human study Thymalin. A report by the authors of the 1997 paper followed 266 older people for six to eight years, some given thymalin, some a pineal preparation and some both, and described lower mortality in those groups than in a control group.¹⁸ Its abstract does not say how participants were allocated or whether assessment was blinded.¹⁸ ClinicalTrials.gov returned no registered study of thymalin.²⁴

Regulatory status

Statements were checked against each authority’s own page on 8 October 2026.

• Thymosin alpha-1 (thymalfasin). Italy’s medicines agency lists Zadaxin as authorized since 1996, and its summary of product characteristics gives one indication: an adjuvant to influenza vaccination in immunocompromised people.¹⁰²⁵ FDA staff stated in 2024 that it is not approved in the United States, Japan or Europe apart from Italy, and that they could not independently verify the company’s reports of approval in countries of the Asia-Pacific region, Latin America, Eastern Europe and the Middle East.¹⁹ An FDA record shows an orphan-drug designation dated 8 January 1998 for DiGeorge anomaly with immune defects, with no approval for that use.²⁶ The FDA’s approved-drug data and Health Canada’s Drug Product Database returned no product.¹¹¹²
• Thymosin beta-4. Searches of Health Canada’s database and the FDA’s approved-drug data for thymosin and for timbetasin, its nonproprietary name, returned no product.¹¹¹²¹⁵ A Health Canada advisory of 9 April 2026 names TB-500 among unauthorized peptide drugs it had seized, and says that a “For Research Use Only” label does not exempt a product from regulatory requirements.²⁷
• Thymalin. The same searches returned no product, and the EMA’s table of centrally authorized medicines has none.¹¹¹²²⁸ The 1997 paper describes it as a pharmaceutical that had been put into practice, and we found no national register we could open to confirm where it is licensed.³

An authorization covers one manufactured medicine in one country, not the same molecule supplied as a research material, which Horizon sells for laboratory research use only. The guide to evidence levels in peptide research sets out how to weigh cell, animal and human findings.