Thymosin α1

PTMA
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPTMA, prothymosin, alpha, TMSA, prothymosin alpha
External IDsOMIM: 188390; MGI: 97803; HomoloGene: 136511; GeneCards: PTMA; OMA:PTMA - orthologs
Orthologs
SpeciesHumanMouse
Entrez

5757

19231

Ensembl

ENSG00000187514

ENSMUSG00000026238

UniProt

P06454

P26350

RefSeq (mRNA)

NM_001099285
NM_002823

NM_008972

RefSeq (protein)

NP_001092755
NP_002814

NP_032998
NP_001347759
NP_001347760

Location (UCSC)Chr 2: 231.71 – 231.71 MbChr 1: 86.53 – 86.53 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
Thymosin α1
Identifiers
  • (4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S,3R)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]propanoyl]amino]propanoyl]amino]-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]propanoyl]amino]-5-[[(1S)-3-amino-1-carboxy-3-oxopropyl]amino]-5-oxopentanoic acid
CAS Number
PubChem CID
Chemical and physical data
FormulaC129H215N33O55
Molar mass3108.315 g·mol−1
3D model (JSmol)
  • CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)C
  • InChI=1S/C129H215N33O55/c1-18-59(10)98(159-114(201)76(36-42-91(181)182)146-120(207)83(53-164)154-121(208)84(54-165)155-127(214)99(63(14)166)160-118(205)80(51-94(187)188)152-123(210)95(56(4)5)156-104(191)62(13)135-102(189)60(11)137-115(202)78(49-92(183)184)151-119(206)82(52-163)138-66(17)169)125(212)161-101(65(16)168)128(215)162-100(64(15)167)126(213)147-70(30-22-26-46-133)109(196)150-79(50-93(185)186)117(204)149-77(47-55(2)3)116(203)142-69(29-21-25-45-132)108(195)144-73(33-39-88(175)176)110(197)141-67(27-19-23-43-130)106(193)140-68(28-20-24-44-131)107(194)145-75(35-41-90(179)180)113(200)157-97(58(8)9)124(211)158-96(57(6)7)122(209)148-74(34-40-89(177)178)111(198)143-71(31-37-86(171)172)105(192)136-61(12)103(190)139-72(32-38-87(173)174)112(199)153-81(129(216)217)48-85(134)170/h55-65,67-84,95-101,163-168H,18-54,130-133H2,1-17H3,(H2,134,170)(H,135,189)(H,136,192)(H,137,202)(H,138,169)(H,139,190)(H,140,193)(H,141,197)(H,142,203)(H,143,198)(H,144,195)(H,145,194)(H,146,207)(H,147,213)(H,148,209)(H,149,204)(H,150,196)(H,151,206)(H,152,210)(H,153,199)(H,154,208)(H,155,214)(H,156,191)(H,157,200)(H,158,211)(H,159,201)(H,160,205)(H,161,212)(H,162,215)(H,171,172)(H,173,174)(H,175,176)(H,177,178)(H,179,180)(H,181,182)(H,183,184)(H,185,186)(H,187,188)(H,216,217)/t59-,60-,61-,62-,63+,64+,65+,67-,68-,69-,70-,71-,72-,73-,74-,75-,76-,77-,78-,79-,80-,81-,82-,83-,84-,95-,96-,97-,98-,99-,100-,101-/m0/s1
  • Key:NZVYCXVTEHPMHE-ZSUJOUNUSA-N

Thymosin α1 is a peptide fragment derived from prothymosin alpha, a protein that in humans is encoded by the PTMA gene.[5]

It was the first of the peptides from Thymosin Fraction 5 to be completely sequenced and synthesized. Unlike β thymosins, to which it is genetically and chemically unrelated, thymosin α1 is produced as a 28-amino acid fragment having the sequence Ac-SDAAVDTSSEITTKDLKEKKEVEEEAEN, which is made from cleavage of a longer, 113-amino acid precursor, prothymosin α.[6]

Function

Thymosin α1 is an agonist for toll-like receptor 2 and toll-like receptor 9 on both myeloid and dendritic antigen-presenting cells, thereby stimulating the adaptive immune response.[7]

Thymosin α1 is believed to be a major component of Thymosin Fraction 5 responsible for the activity of that preparation in restoring immune function in animals lacking thymus glands. It has been found to enhance cell-mediated immunity in humans as well as experimental animals.[8]

Therapeutic application

Thymosin α1 is approved in some countries for the treatment of Hepatitis B and C, and it is also used to boost the immune response in the treatment of other diseases.[9][10] The synthetic version of Thymosin α1 is known as Thymalfasin and is sold under the brand name Zadaxin.[11]

Thymosin α1 is usually administered by subcutaneous injection.[7]

Clinical studies

Clinical trials suggest thymosin α1 may be useful in cystic fibrosis, septic shock,[12] acute respiratory distress syndrome, peritonitis, pancreatitis,[13] acute cytomegalovirus infection, TB, severe acute respiratory syndrome, and lung infections in critically ill patients.,[10][14] and for chronic hepatitis B.[15][16][17]

For hospitalized COVID-19 patients, thymosin α1 is not generally thought to reduce mortality or length of hospitalization,[18] though studies have shown conflicting results.[19]

It has been studied for possible use in treating cancer (e.g. with chemotherapy).[20]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000187514 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026238 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Manrow RE, Leone A, Krug MS, Eschenfeldt WH, Berger SL (Jul 1992). "The human prothymosin alpha gene family contains several processed pseudogenes lacking deleterious lesions". Genomics. 13 (2): 319–31. doi:10.1016/0888-7543(92)90248-Q. PMID 1612591.
  6. ^ Garaci E (September 2007). "Thymosin alpha1: a historical overview". Ann. N. Y. Acad. Sci. 1112: 14–20. doi:10.1196/annals.1415.039. PMID 17567941. S2CID 222082988.
  7. ^ a b Dominari A, Hathaway D, Baralt D (2020). "Thymosin alpha 1: A comprehensive review of the literature". World Journal of Virology. 9 (5): 67–78. doi:10.5501/wjv.v9.i5.67. PMC 7747025. PMID 33362999.
  8. ^ Wara DW, Goldstein AL, Doyle NE, Ammann AJ (January 1975). "Thymosin activity in patients with cellular immunodeficiency". N. Engl. J. Med. 292 (2): 70–4. doi:10.1056/NEJM197501092920204. PMID 1078552.
  9. ^ Garaci E, Favalli C, Pica F, et al. (September 2007). "Thymosin alpha 1: from bench to bedside". Ann. N. Y. Acad. Sci. 1112 (1): 225–34. Bibcode:2007NYASA1112..225G. doi:10.1196/annals.1415.044. PMID 17600290. S2CID 28283520.
  10. ^ a b Goldstein AL, Goldstein AL (May 2009). "From lab to bedside: emerging clinical applications of thymosin alpha 1". Expert Opin Biol Ther. 9 (5): 593–608. doi:10.1517/14712590902911412. PMID 19392576. S2CID 71893579.
  11. ^ Quagliata M, Papini AM, Rovero P (2023). "Therapeutic applications of thymosin peptides: A patent landscape 2018-present". Expert Opinion on Therapeutic Patents. 33 (12): 865–873. doi:10.1080/13543776.2023.2298833. PMID 38131310.
  12. ^ Gu B, Zhou Y, Nie Y, Wang L, Liang L, Liao Z, Wen J, Guan X, Chen M, Wu J, Pei F (2025). "Efficacy of thymosin α1 for sepsis: A systematic review and meta-analysis of randomized controlled trials". Frontiers in Cellular and Infection Microbiology. 15 1673959. doi:10.3389/fcimb.2025.1673959. PMC 12440967. PMID 40969554.
  13. ^ Tian Y, Yao J, Ma Y, Zhang P, Zhou X, Xie W, Tang W (2025). "Thymosin alpha 1 alleviates inflammation and prevents infection in patients with severe acute pancreatitis through immune regulation: A systematic review and meta-analysis". Frontiers in Immunology. 16 1571456. doi:10.3389/fimmu.2025.1571456. PMC 12208829. PMID 40599771.
  14. ^ Cao A, Feng F, Zhou X (2024). "Thymosin Alpha 1 Plus Routine Treatment for the Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis". Journal of the College of Physicians and Surgeons Pakistan. 34 (12): 1497–1507. doi:10.29271/jcpsp.2024.12.1497. PMID 39648386.
  15. ^ Wu X, Jia J, You H (2015). "Thymosin alpha-1 treatment in chronic hepatitis B". Expert Opinion on Biological Therapy. 15: 129–132. doi:10.1517/14712598.2015.1007948. PMID 25640173. S2CID 41148652.
  16. ^ Dinetz E, Lee E (2024). "Comprehensive Review of the Safety and Efficacy of Thymosin Alpha 1 in Human Clinical Trials". Alternative Therapies in Health and Medicine. 30 (1): 6–12. PMID 38308608.
  17. ^ Simonova MA, Ivanov I, Shoshina NS, Komyakova AM, Makarov DA, Baranovskii DS, Klabukov ID, Telepenina KP, Atiakshin DA, Shegay PV, Kaprin AD, Stepanenko VN (2025). "Aging and Thymosin Alpha-1". International Journal of Molecular Sciences. 26 (23) 11470. doi:10.3390/ijms262311470. PMC 12692621. PMID 41373628.
  18. ^ Shang W, Zhang B, Li Y (2023). "Thymosin alpha1 use in adult COVID-19 patients: A systematic review and meta-analysis on clinical outcomes". International Immunopharmacology. 114 109584. doi:10.1016/j.intimp.2022.109584. PMC 9754924. PMID 36527881.
  19. ^ Soeroto AY, Suryadinata H, Yanto TA, Hariyanto TI (2023). "The efficacy of thymosin alpha-1 therapy in moderate to critical COVID-19 patients: A systematic review, meta-analysis, and meta-regression". Inflammopharmacology. 31 (6): 3317–3325. doi:10.1007/s10787-023-01354-2. PMID 37845598.
  20. ^ Garaci E, Pica F, Rasi G, Favalli C (2000). "Thymosin alpha 1 in the treatment of cancer: from basic research to clinical application". Int J Immunopharmacol. 22 (12): 1067–76. doi:10.1016/s0192-0561(00)00075-8. PMID 11137613.

Further reading

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