Thymalfasin
[CAS# 69440-99-9]

Identification

• Classification: Biochemical >> Peptide
• Name: Thymalfasin
• Synonyms: Ac-DL-Ser-DL-Asp-DL-Ala-DL-Ala-DL-Val-DL-Asp-DL-xiThr-DL-Ser-DL-Ser-DL-Glu-DL-xiIle-DL-xiThr-DL-xiThr-DL-Lys-DL-Asp-DL-Leu-DL-Lys-DL-Glu-DL-Lys-DL-Lys-DL-Glu-DL-Val-DL-Val-DL-Glu-DL-Glu-DL-Ala-DL-Glu-DL-Asn-OH; 4-[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[2-[2-[[2-[(2-acetamido-3-hydroxypropanoyl)amino]-3-carboxypropanoyl]amino]propanoylamino]propanoylamino]-3-methylbutanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-4-carboxybutanoyl]amino]-3-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxybutanoyl]amino]-6-aminohexanoyl]amino]-3-carboxypropanoyl]amino]-4-methylpentanoyl]amino]-6-aminohexanoyl]amino]-4-carboxybutanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-4-carboxybutanoyl]amino]-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-4-carboxybutanoyl]amino]-4-carboxybutanoyl]amino]propanoylamino]-5-[(3-amino-1-carboxy-3-oxopropyl)amino]-5-oxopentanoic acid
• Protein Sequence: SDAAVDXSSEXXXKDLKEKKEVVEEAEN
• Molecular Formula: C₁₂₉H₂₁₅N₃₃O₅₅
• Molecular Weight: 3108.28
• CAS Registry Number: 69440-99-9
• SMILES: CCC(C)C(C(=O)NC(C(C)O)C(=O)NC(C(C)O)C(=O)NC(CCCCN)C(=O)NC(CC(=O)O)C(=O)NC(CC(C)C)C(=O)NC(CCCCN)C(=O)NC(CCC(=O)O)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCC(=O)O)C(=O)NC(C(C)C)C(=O)NC(C(C)C)C(=O)NC(CCC(=O)O)C(=O)NC(CCC(=O)O)C(=O)NC(C)C(=O)NC(CCC(=O)O)C(=O)NC(CC(=O)N)C(=O)O)NC(=O)C(CCC(=O)O)NC(=O)C(CO)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C(CC(=O)O)NC(=O)C(C(C)C)NC(=O)C(C)NC(=O)C(C)NC(=O)C(CC(=O)O)NC(=O)C(CO)NC(=O)C

Properties

• Density: 1.4±0.1 g/cm³ Calc.^*
• Boiling point: 2899.7±65.0 ºC 760 mmHg (Calc.)^*
• Flash point: 1707.5±34.3 ºC (Calc.)^*
• Index of refraction: 1.563 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Discovory and Applicatios

Thymalfasin is a synthetic peptide that corresponds to a naturally occurring thymic hormone fragment involved in immune regulation. It is chemically identical to thymosin α1, a 28–amino acid peptide originally isolated from thymus tissue during investigations into thymic factors that influence T-cell development and function. The discovery of thymosin peptides dates back to the 1960s and 1970s, when researchers sought to understand how the thymus contributes to immune competence. Through fractionation of thymic extracts, a group of small peptides was identified, among which thymosin α1 emerged as a well-defined component with reproducible biological activity. Thymalfasin was later produced by chemical synthesis to provide a consistent and purified form suitable for experimental and clinical use.

The identification of thymosin α1 as an immunologically active peptide marked an important step in thymus research. Early studies demonstrated that this peptide could influence the maturation and differentiation of T lymphocytes, enhance lymphocyte responses to antigens, and modulate cytokine production. Because extraction from animal thymus tissue yielded heterogeneous mixtures, synthetic production became essential. Thymalfasin was developed as a synthetic equivalent that maintained the same amino acid sequence and biological properties as the naturally occurring peptide, allowing systematic investigation and standardized application.

In experimental immunology, thymalfasin has been used extensively as a tool to study immune system regulation. Research has shown that it can enhance T-cell function, promote the activity of natural killer cells, and influence the balance of cytokines involved in innate and adaptive immune responses. These properties led to interest in its potential therapeutic applications, particularly in conditions characterized by impaired or dysregulated immunity. Thymalfasin has been investigated in the context of viral infections, immune deficiencies, and as an adjunct in cancer therapy, where immune modulation plays a critical role.

One of the most significant applications of thymalfasin has been in the treatment of chronic viral infections. Clinical studies have examined its use in chronic hepatitis B and hepatitis C, where it has been administered to support immune-mediated viral clearance, either alone or in combination with antiviral agents. In these settings, thymalfasin has been reported to enhance host immune responses rather than acting directly on the virus. This immunomodulatory mechanism distinguishes it from conventional antiviral drugs and has contributed to its evaluation as an adjunctive therapy.

Thymalfasin has also been explored in oncology as an immune adjuvant. By promoting T-cell activity and improving immune surveillance, it has been studied as a supportive treatment alongside chemotherapy or radiotherapy. The rationale for this application is based on observations that cancer and cytotoxic treatments can suppress immune function, and that restoring immune responsiveness may improve patient outcomes. Beyond oncology and virology, thymalfasin has been investigated in vaccine responses, where it has been evaluated for its ability to enhance immunogenicity, particularly in populations with weaker immune responses.

From a pharmaceutical perspective, thymalfasin is valued for its defined structure, reproducible synthesis, and relatively favorable safety profile. Its peptide nature means it is metabolized into amino acids, reducing concerns associated with long-term accumulation. As a result, it has been approved or used clinically in several countries for specific indications related to immune modulation, while continuing to be studied in broader immunological research.

Overall, thymalfasin represents a successful example of translating a naturally occurring thymic peptide into a synthetic immunomodulatory agent. Its discovery stemmed from fundamental research into thymus biology, and its applications have expanded into clinical and experimental fields focused on enhancing and regulating immune function.

References

Goldstein G, Scheid MP, Hammerling U, Boyse EA (1975) Isolation of a polypeptide thymic hormone. Proceedings of the National Academy of Sciences of the United States of America 72 1 11–15 DOI: 10.1073/pnas.72.1.11