# Thymalin

> Thymalin is a thymus-derived peptide complex, a polypeptide extract of thymus tissue described in the literature as regulating immune function. The dipeptides Lys-Glu (KE) and Glu-Trp (EW) are reported as its active components. Thymalin has been studied in cell culture, rat models and clinical reports on aging and severe COVID-19, and it is not approved by the FDA for any use.

Canonical: https://peptideproperties.com/compounds/thymalin/

## Identity

- **Class:** Short Peptide Bioregulators
- **Also known as:** Thymus peptide complex
- **Sequence notes:** Not a single sequence: thymalin is a thymus-derived polypeptide complex. The dipeptides Lys-Glu (KE) and Glu-Trp (EW) are reported as active components.

## Key facts

- Class: thymus-derived peptide complex in the short peptide bioregulator family
- Composition: polypeptide extract of thymus; not a single defined molecule
- Reported active components: dipeptides Lys-Glu (KE) and Glu-Trp (EW)
- Research focus: T-cell maturation, immune aging, COVID-19 and tissue repair models
- Evidence: in vitro, rat and fetal tissue studies plus clinical reports
- No PubChem record; no single formula or molecular weight
- Regulatory status: not approved by the FDA for any use

## What Is Thymalin?

Thymalin is a polypeptide complex isolated from the thymus and described in the literature as regulating functions of the immune system[1]. Researchers characterize it as an immunomodulatory preparation containing a polypeptide extract of thymus, with the dipeptides Lys-Glu (KE) and Glu-Trp (EW) identified as active substances[2].Thymalin is one of several complex peptide preparations manufactured from extracts of different tissues. Among its reported effects, those related to stimulation of immunity are the most prominent, and they have been linked by the originating research group to anticarcinogenic and geroprotective activity[3].Because thymalin is a mixture rather than a single compound, it has no single sequence, formula or molecular weight. It is distinct from thymosin alpha-1 (thymalfasin), which is a defined 28-amino-acid peptide.

## Chemical Structure and Molecular Identity

Thymalin has no single chemical structure: it is a polypeptide extract of thymus tissue[2]. No PubChem compound record was identified for it, so this page lists no formula, molecular weight, CAS number or InChIKey.The originating research program analyzed the amino acid composition of its tissue-derived preparations and used the results to design short synthetic peptides. For the thymus, these were dipeptides that stimulated outgrowth of thymic explants in vitro[3]. A 2023 study names Lys-Glu and Glu-Trp as the active substances of thymalin[2].Reported componentSequenceActivity described in the source abstractKE dipeptideLys-GluStimulates cellular immunity and nonspecific resistance; activates macrophages, blood lymphocytes, thymocytes and neutrophilsEW dipeptideGlu-TrpReduces angiotensin-induced vasoconstriction and preserves endothelium-dependent vascular relaxationThese two dipeptides are also studied individually as synthetic compounds, under the names vilon (Lys-Glu) and thymogen (Glu-Trp). Thymalin itself, however, is the whole extract rather than either dipeptide alone.

## Research History and Development

Thymalin appears in the indexed literature from at least 2002 through 2024, with early work on aging and immunity and later work on COVID-19 and tissue repair. Five of the twelve papers reviewed here list V. Kh. Khavinson as an author; the recent tumor and bone-repair studies come from other groups.In 2002, a review described the technology used to manufacture complex peptide preparations from tissue extracts and summarized thymalin's immune-related effects[3]. The same year, an organotypic culture study compared preparations from the cerebral cortex, pineal gland, liver and thymus, together with synthetic peptides such as cortagen, epitalon, livagen and vilon, on explants from rats of various ages and reported tissue-specific effects[4]. A long-term clinical observation of older adults was also published in 2002[5], and a 2003 study traced thymalin-positive cells in human fetal respiratory organs[6].Later work included a 2010 review of thymus-pineal interactions during aging[7], a 2016 review of radiation cytogenetics after the Chornobyl accident[8], a 2018 rat tumor study[9], COVID-19-related studies from 2020 to 2023[1][10][2], and two 2024 rat studies of jaw bone repair[11][12].

## Mechanisms Studied in Research

Research attributes thymalin's activity mainly to effects on T-lymphocyte maturation and immune cell activity, with proposed gene-regulatory actions of its dipeptide components. Most mechanistic data are in vitro or computational.
### T-cell differentiation
In cultures of human hematopoietic stem cells, thymalin reduced expression of CD44, a stem cell marker, and CD117, a marker of an intermediate differentiation stage, by two- to threefold, and increased expression of CD28, a marker of mature T lymphocytes, by 6.8-fold[1]. The authors interpreted this as indirect evidence that thymalin stimulates differentiation of CD117-positive cells into mature CD28-positive T cells.
### Dipeptide components and DNA
A 2023 study used molecular modeling and docking to examine interactions between the KE and EW dipeptides and double-stranded DNA, and bioinformatics searches of promoter sequences and pathway databases to identify genes linked to COVID-19 that the dipeptides might influence[2]. The available abstract describes this approach but not specific conclusions.
### Thymus-pineal interactions
A 2010 review concluded that pineal peptides had a stronger geroprotective effect on thymic involution than thymic peptides such as thymalin and thymogen had on pineal involution, and proposed immunoendocrine cooperation through transcriptional activation as the key mechanism[7].
### Radiation-induced chromosome damage
A review of Chornobyl-related research reported that thymalin could modify radiation-induced cytogenetic effects in peripheral blood lymphocytes from healthy individuals, with either protective or sensitizing action depending on concentration, cell radiosensitivity, radiation dose and the relative biological effectiveness of the radiation[8].

## Key Findings From Published Studies

Reported findings include T-cell maturation in vitro, antitumor and bone-repair effects in rats, and immune and survival outcomes in clinical reports. The clinical abstracts do not describe randomized, blinded designs.
### Animal studies
In outbred rats with transplanted sarcoma 45, thymalin given under an activation-therapy regimen was followed by tumor growth arrest and regression in more than half of the animals and 78% growth suppression in the rest, alongside increased lymphoproliferative activity in the thymus[9].In 48 WAG rats with a surgically created defect in the lower jaw, divided into four groups of 12, filling the defect with a hydroxyapatite-containing bone graft material and injecting thymalin into the surrounding soft tissue activated reparative bone formation, with faster clearance of necrotic tissue and fewer neutrophils[11]. A companion study found increased T-lymphocyte counts in the healing tissue from day 3 through day 28[12].
### Fetal tissue
An immunohistochemical study of early human fetal respiratory organs found thymalin-positive cells in young airway epithelial cells and diffusely in the alveolar region, along with mature CD3, CD4 and CD8 T cells in the lungs before a thymic microenvironment was present[6]. The authors proposed that these immune elements help protect the fetus locally from maternal cells and infectious agents.
### Clinical reports
In a 6- to 8-year observation of 266 older adults, the authors reported a 2.0- to 2.1-fold lower mortality among thymalin-treated participants than in controls, and a 2.5-fold lower mortality when thymalin was combined with a pineal peptide preparation, along with a lower incidence of acute respiratory disease[5].In middle-aged and elderly patients with severe COVID-19, hospital mortality was 40.9% with basic therapy, 28.4% with added tocilizumab and 20.6% with added thymalin. In the thymalin group, lymphocyte and monocyte counts doubled, the neutrophil-to-lymphocyte ratio halved, and fibrinogen, lactate dehydrogenase and D-dimer fell[10]. The abstract does not report group sizes or how patients were assigned.Because thymalin is a tissue-derived mixture rather than a single molecule, researchers typically review certificates of analysis for peptide profile, purity and identity testing.

## Regulatory and Research Status

Thymalin is not approved by the U.S. Food and Drug Administration for any medical use. In the cited literature, authors describe it as a drug used in therapy of acute respiratory distress syndrome, chronic obstructive lung disease and other immune conditions[1][2].Statements in the source abstracts, such as thymalin being an immunoprotective peptide drug for COVID-19 prevention[1] or having high geroprotective efficacy[5], are the authors' conclusions. They come from studies whose abstracts do not describe randomized, controlled designs.Open research questions include the standardized composition of the extract, the contribution of individual components beyond the KE and EW dipeptides, and confirmation of the clinical findings in randomized trials.

## FAQ

**What is thymalin?**
Thymalin is a peptide complex extracted from the thymus and described in the literature as an immunomodulatory preparation that regulates immune function. It is a mixture rather than a single molecule, and the dipeptides Lys-Glu (KE) and Glu-Trp (EW) are reported as its active components. It has been studied in cell culture, rat models and clinical reports.

**Is thymalin the same as thymosin alpha-1?**
No. Thymalin is a polypeptide extract of thymus tissue, a mixture with no single sequence or molecular weight. Thymosin alpha-1 (thymalfasin) is a single defined peptide of 28 amino acids. Both are associated with the thymus and immune research, but they are different materials and should not be treated as interchangeable.

**Is thymalin FDA approved?**
No. Thymalin is not approved by the U.S. Food and Drug Administration for any medical use. Authors of the published studies describe it as a drug used in therapy of respiratory and immune conditions, but the clinical abstracts available do not describe randomized, blinded trials, and it has no U.S. regulatory approval.

**What are the active components of thymalin?**
A 2023 study names the dipeptides Lys-Glu (KE) and Glu-Trp (EW) as active substances of thymalin. According to that abstract, KE stimulates cellular immunity and activates macrophages, lymphocytes, thymocytes and neutrophils, while EW reduces angiotensin-induced vasoconstriction. Thymalin itself is a broader polypeptide extract of thymus tissue.

**How is thymalin different from thymogen?**
Thymogen is a synthetic dipeptide, Glu-Trp, with a single defined structure. Thymalin is a thymus-derived polypeptide extract in which Glu-Trp is reported as one of two active dipeptides, the other being Lys-Glu. Both have been studied as thymic peptides in the same research program, including a review of their effects on pineal involution.

**What does the research on thymalin show?**
In vitro, thymalin increased markers of mature T cells in human hematopoietic stem cell cultures. In rats it was associated with tumor regression in a sarcoma model and faster jaw bone repair. Clinical reports describe lower mortality in older adults and in severe COVID-19, but these abstracts do not describe randomized, blinded designs.

## References

1. Khavinson VK, Linkova NS, Kvetnoy IM, et al. Thymalin: Activation of Differentiation of Human Hematopoietic Stem Cells. Bulletin of experimental biology and medicine 2020. PMID: 33237528
2. Linkova N, Khavinson V, Diatlova A, et al. The Influence of KE and EW Dipeptides in the Composition of the Thymalin Drug on Gene Expression and Protein Synthesis Involved in the Pathogenesis of COVID-19. International journal of molecular sciences 2023. PMID: 37686182
3. Khavinson VKh. Peptides and Ageing. Neuro endocrinology letters 2002. PMID: 12374906
4. Khavinson VKh, Malinin VV, Chalisova NI, et al. [Tissue-specific action of peptides in tissue culture of rats of various ages]. Advances in gerontology = Uspekhi gerontologii 2002. PMID: 12096446
5. Khavinson VKh, Morozov VG. [Geroprotective effect of thymalin and [pineal peptide extract]]. Advances in gerontology = Uspekhi gerontologii 2002. PMID: 12577695
6. Khlystova ZS, Kalinina II, Shmeleva SP. Thymalin in developing respiratory organs of human fetus. Bulletin of experimental biology and medicine 2003. PMID: 12937685
7. Lin'kova NS, Poliakova VO, Trofimov AV, et al. [Influence of peptides from pineal gland on thymus function at aging]. Advances in gerontology = Uspekhi gerontologii 2010. PMID: 21510076
8. Domina EA. Chornobyl catastrophe: cytogenetic effects of low dose ionizing radiation and their modification. Experimental oncology 2016. PMID: 28230819
9. Zhukova GV, Schikhlyarova AI, Barteneva TA, et al. Effect of Thymalin on the Tumor and Thymus under Conditions of Activation Therapy In Vivo. Bulletin of experimental biology and medicine 2018. PMID: 29797130
10. Kuznik BI, Shapovalov KG, Smolyakov YN, et al. [Morphological compound and indicators of the blood clotting system in severe COVID-19 patients of middle aged and elderly during treatment of Tocilizumab and Thymalin.]. Advances in gerontology = Uspekhi gerontologii 2022. PMID: 36169363
11. Boiko AA, Malanchuk VA, Myroshnychenko MS. Reparative osteogenesis in mandible in cases of filling a bone defect with hydroxyapatite-containing osteotropic material and injecting the surrounding soft tissues with thymalin: experimental and morphological study. Wiadomosci lekarskie (Warsaw, Poland : 1960) 2024. PMID: 38431810
12. Boiko AA, Malanchuk VA, Myroshnychenko MS, et al. Expression features of T-lymphocytes, B-lymphocytes and macrophages in the post-traumatic regenerate of the mandible rats under conditions of filling a bone defect with hydroxyapatite-containing osteotropic material and thymalin injecting the surrounding soft tissues. Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego 2024. PMID: 38642352