{{Short description|Protein-coding gene in the species Homo sapiens}} {{cs1 config|name-list-style=vanc}} {{Infobox_gene}} {{Infobox drug | image = Thymalfasin_structure.png | width = 320 <!-- Clinical data --> | tradename = | pregnancy_category = | routes_of_administration = | class = | ATC_prefix = | ATC_suffix = | ATC_supplemental = <!-- Legal status --> | legal_status = <!-- Pharmacokinetic data --> | bioavailability = | protein_bound = | metabolism = | metabolites = | onset = | elimination_half-life = | duration_of_action = | excretion = <!-- Identifiers --> | CAS_number = 62304-98-7 | PubChem = 16130571 | IUPHAR_ligand = | DrugBank = | ChemSpiderID = | UNII = | KEGG = | ChEBI = | ChEMBL = | NIAID_ChemDB = | PDB_ligand = <!-- Chemical and physical data --> | IUPAC_name = <nowiki>(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</nowiki> | C = 129 | H = 215 | N = 33 | O = 55 | StdInChI = 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 | StdInChIKey = NZVYCXVTEHPMHE-ZSUJOUNUSA-N | SMILES = 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 }} '''Thymosin α<sub>1</sub>''' is a peptide fragment derived from '''prothymosin alpha''', a protein that in humans is encoded by the ''PTMA'' gene.<ref name="pmid1612591">{{cite journal |vauthors=Manrow RE, Leone A, Krug MS, Eschenfeldt WH, Berger SL | title = The human prothymosin alpha gene family contains several processed pseudogenes lacking deleterious lesions | journal = Genomics | volume = 13 | issue = 2 | pages = 319–31 |date=Jul 1992 | pmid = 1612591 | doi =10.1016/0888-7543(92)90248-Q | url = https://zenodo.org/record/1258589 }}</ref>
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 α<sub>1</sub> 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.<ref name="pmid17567941">{{cite journal | author = Garaci E | title = Thymosin alpha1: a historical overview | journal = Ann. N. Y. Acad. Sci. | volume = 1112 | pages = 14–20 |date=September 2007 | pmid = 17567941 | doi = 10.1196/annals.1415.039 | s2cid = 222082988 }}</ref>
== Function == Thymosin α<sub>1</sub> 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.<ref name="pmid33362999" />
Thymosin α<sub>1</sub> 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.<ref>{{cite journal |vauthors=Wara DW, Goldstein AL, Doyle NE, Ammann AJ |title=Thymosin activity in patients with cellular immunodeficiency |journal=N. Engl. J. Med. |volume=292 |issue=2 |pages=70–4 |date=January 1975 |pmid=1078552 |doi= 10.1056/NEJM197501092920204}}</ref>
== Therapeutic application == Thymosin α<sub>1</sub> 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.<ref>{{cite journal |vauthors=Garaci E, Favalli C, Pica F, etal |title=Thymosin alpha 1: from bench to bedside |journal=Ann. N. Y. Acad. Sci. |volume=1112 |pages=225–34 |date=September 2007 |issue=1 |pmid=17600290 |doi=10.1196/annals.1415.044 |bibcode=2007NYASA1112..225G |s2cid=28283520 }}</ref><ref name=Goldstein2009>{{cite journal |vauthors=Goldstein AL, Goldstein AL |title=From lab to bedside: emerging clinical applications of thymosin alpha 1 |journal=Expert Opin Biol Ther |volume=9 |issue=5 |pages=593–608 |date=May 2009 |pmid=19392576 |doi=10.1517/14712590902911412 |s2cid=71893579 }}</ref> The synthetic version of Thymosin α<sub>1</sub> is known as '''Thymalfasin''' and is sold under the brand name '''Zadaxin'''.<ref>{{cite journal | title=Therapeutic applications of thymosin peptides: A patent landscape 2018-present | journal=Expert Opinion on Therapeutic Patents | date=2023 | volume=33 | issue=12 | pages=865–873 | doi=10.1080/13543776.2023.2298833 | pmid=38131310 | vauthors = Quagliata M, Papini AM, Rovero P }}</ref>
Thymosin α<sub>1</sub> is usually administered by subcutaneous injection.<ref name="pmid33362999">{{cite journal | vauthors = Dominari A, Hathaway D, Baralt D | title = Thymosin alpha 1: A comprehensive review of the literature | journal = World Journal of Virology | volume = 9 | issue=5 | pages = 67–78| date = 2020 | doi = 10.5501/wjv.v9.i5.67 | doi-access = free | pmc = 7747025 | pmid = 33362999 }}</ref>
===Clinical studies=== Clinical trials suggest thymosin α<sub>1</sub> may be useful in cystic fibrosis, septic shock,<ref>{{cite journal | title=Efficacy of thymosin α1 for sepsis: A systematic review and meta-analysis of randomized controlled trials | journal=Frontiers in Cellular and Infection Microbiology | date=2025 | volume=15 | article-number=1673959 | doi=10.3389/fcimb.2025.1673959 | doi-access=free | pmid=40969554 | vauthors = Gu B, Zhou Y, Nie Y, Wang L, Liang L, Liao Z, Wen J, Guan X, Chen M, Wu J, Pei F | pmc=12440967 }}</ref> acute respiratory distress syndrome, peritonitis, pancreatitis,<ref>{{cite journal | title=Thymosin alpha 1 alleviates inflammation and prevents infection in patients with severe acute pancreatitis through immune regulation: A systematic review and meta-analysis | journal=Frontiers in Immunology | date=2025 | volume=16 | article-number=1571456 | doi=10.3389/fimmu.2025.1571456 | doi-access=free | pmid=40599771 | pmc=12208829 | vauthors = Tian Y, Yao J, Ma Y, Zhang P, Zhou X, Xie W, Tang W }}</ref> acute cytomegalovirus infection, TB, severe acute respiratory syndrome, and lung infections in critically ill patients.,<ref name=Goldstein2009/><ref>{{cite journal | title=Thymosin Alpha 1 Plus Routine Treatment for the Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis | journal=Journal of the College of Physicians and Surgeons Pakistan | date=2024 | volume=34 | issue=12 | pages=1497–1507 | doi=10.29271/jcpsp.2024.12.1497 | pmid=39648386 | vauthors = Cao A, Feng F, Zhou X | doi-access=free }}</ref> and for chronic hepatitis B.<ref name=Wu2015>{{cite journal|doi=10.1517/14712598.2015.1007948 | volume=15 | title=Thymosin alpha-1 treatment in chronic hepatitis B | year=2015 | journal=Expert Opinion on Biological Therapy | pages=129–132 | vauthors=Wu X, Jia J, You H| pmid=25640173 | doi-access= | s2cid=41148652 }}</ref><ref>{{cite journal | title=Comprehensive Review of the Safety and Efficacy of Thymosin Alpha 1 in Human Clinical Trials | journal=Alternative Therapies in Health and Medicine | date=2024 | volume=30 | issue=1 | pages=6–12 | pmid=38308608 | vauthors = Dinetz E, Lee E }}</ref><ref>{{cite journal | title=Aging and Thymosin Alpha-1 | journal=International Journal of Molecular Sciences | date=2025 | volume=26 | issue=23 | article-number=11470 | doi=10.3390/ijms262311470 | doi-access=free | pmid=41373628 | pmc=12692621 | vauthors = Simonova MA, Ivanov I, Shoshina NS, Komyakova AM, Makarov DA, Baranovskii DS, Klabukov ID, Telepenina KP, Atiakshin DA, Shegay PV, Kaprin AD, Stepanenko VN }}</ref>
For hospitalized COVID-19 patients, a 2023 review concluded thymosin α<sub>1</sub> was not effective in reducing mortality or length of hospitalization.<ref name="pmid36527881">{{cite journal | vauthors = Shang W, Zhang B, Li Y | title = Thymosin alpha1 use in adult COVID-19 patients: A systematic review and meta-analysis on clinical outcomes | journal = International Immunopharmacology | volume = 114 | article-number = 109584 | date = 2023 | doi = 10.1016/j.intimp.2022.109584 | doi-access = free | pmc = 9754924| pmid = 36527881 }}</ref> A subsequent 2023 review contradicted this, showing a reduction in mortality but not length of stay.<ref>{{cite journal | title=The efficacy of thymosin alpha-1 therapy in moderate to critical COVID-19 patients: A systematic review, meta-analysis, and meta-regression | journal=Inflammopharmacology | date=2023 | volume=31 | issue=6 | pages=3317–3325 | doi=10.1007/s10787-023-01354-2 | pmid=37845598 | vauthors = Soeroto AY, Suryadinata H, Yanto TA, Hariyanto TI }}</ref>
It has been studied for possible use in treating cancer (e.g. with chemotherapy).<ref name=Garaci2000>{{cite journal| pmid=11137613 | volume=22 | title=Thymosin alpha 1 in the treatment of cancer: from basic research to clinical application | year=2000 | journal=Int J Immunopharmacol | pages=1067–76 | vauthors=Garaci E, Pica F, Rasi G, Favalli C| issue=12 | doi=10.1016/s0192-0561(00)00075-8 }}</ref>
==See also== * Humanin * MOTS-c * Thymosins * TB-500
==References== {{reflist}}
==Further reading== {{refbegin | 2}} *{{cite journal |vauthors=Martini PG, Katzenellenbogen BS |title=Modulation of estrogen receptor activity by selective coregulators. |journal=J. Steroid Biochem. Mol. Biol. |volume=85 |issue= 2–5 |pages= 117–22 |year= 2003 |pmid= 12943695 |doi=10.1016/S0960-0760(03)00207-3 |s2cid=32374864 }} *{{cite journal |vauthors=Barcia MG, Castro JM, Jullien CD, etal |title=Prothymosin alpha is phosphorylated by casein kinase-2. |journal=FEBS Lett. |volume=312 |issue= 2–3 |pages= 152–6 |year= 1992 |pmid= 1426245 |doi=10.1016/0014-5793(92)80924-6 |s2cid=84760219 |doi-access=free |bibcode=1992FEBSL.312..152B }} *{{cite journal |vauthors=Baxevanis CN, Thanos D, Reclos GJ, etal |title=Prothymosin alpha enhances human and murine MHC class II surface antigen expression and messenger RNA accumulation. |journal=J. Immunol. |volume=148 |issue= 7 |pages= 1979–84 |year= 1992 |doi=10.4049/jimmunol.148.7.1979 |pmid= 1545115 |s2cid=36407216 |doi-access=free }} *{{cite journal |vauthors=Gallego R, Rosón E, García-Caballero T, etal |title=Prothymosin alpha expression in lymph nodes and tonsils: an optical and ultrastructural study. |journal=Acta Anat (Basel) |volume=143 |issue= 3 |pages= 219–22 |year= 1992 |pmid= 1632187 |doi=10.1159/000147251 }} *{{cite journal |vauthors=Cordero OJ, Sarandeses CS, López JL, etal |title=Prothymosin alpha enhances interleukin 2 receptor expression in normal human T-lymphocytes. |journal=Int. J. Immunopharmacol. |volume=13 |issue= 8 |pages= 1059–65 |year= 1992 |pmid= 1814846 |doi=10.1016/0192-0561(91)90156-2 }} *{{cite journal |vauthors=Watts JD, Cary PD, Sautiere P, Crane-Robinson C |title=Thymosins: both nuclear and cytoplasmic proteins. |journal=Eur. J. Biochem. |volume=192 |issue= 3 |pages= 643–51 |year= 1990 |pmid= 2209614 |doi=10.1111/j.1432-1033.1990.tb19271.x |doi-access=free }} *{{cite journal |vauthors=Eschenfeldt WH, Manrow RE, Krug MS, Berger SL |title=Isolation and partial sequencing of the human prothymosin alpha gene family. Evidence against export of the gene products. |journal=J. Biol. Chem. |volume=264 |issue= 13 |pages= 7546–55 |year= 1989 |doi=10.1016/S0021-9258(18)83269-0 |pmid= 2708378 |doi-access=free }} *{{cite journal |vauthors=Gómez-Márquez J, Segade F, Dosil M, etal |title=The expression of prothymosin alpha gene in T lymphocytes and leukemic lymphoid cells is tied to lymphocyte proliferation. |journal=J. Biol. Chem. |volume=264 |issue= 15 |pages= 8451–4 |year= 1989 |doi=10.1016/S0021-9258(18)81807-5 |pmid= 2785990 |doi-access=free }} *{{cite journal |vauthors=Goodall GJ, Dominguez F, Horecker BL |title=Molecular cloning of cDNA for human prothymosin alpha. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=83 |issue= 23 |pages= 8926–8 |year= 1987 |pmid= 3466166 |doi=10.1073/pnas.83.23.8926 | pmc=387046 |doi-access=free }} *{{cite journal |vauthors=Eschenfeldt WH, Berger SL |title=The human prothymosin alpha gene is polymorphic and induced upon growth stimulation: evidence using a cloned cDNA. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=83 |issue= 24 |pages= 9403–7 |year= 1987 |pmid= 3467312 |doi=10.1073/pnas.83.24.9403 | pmc=387146 |doi-access=free }} *{{cite journal |vauthors=Panneerselvam C, Haritos AA, Caldarella J, Horecker BL |title=Prothymosin alpha in human blood. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=84 |issue= 13 |pages= 4465–9 |year= 1987 |pmid= 3474615 |doi=10.1073/pnas.84.13.4465 | pmc=305110 |bibcode=1987PNAS...84.4465P |doi-access=free }} *{{cite journal |vauthors=Pan LX, Haritos AA, Wideman J, etal |title=Human prothymosin alpha: amino acid sequence and immunologic properties. |journal=Arch. Biochem. Biophys. |volume=250 |issue= 1 |pages= 197–201 |year= 1986 |pmid= 3532956 |doi=10.1016/0003-9861(86)90717-4 }} *{{cite journal |vauthors=Kubota S, Adachi Y, Copeland TD, Oroszlan S |title=Binding of human prothymosin alpha to the leucine-motif/activation domains of HTLV-I Rex and HIV-1 Rev. |journal=Eur. J. Biochem. |volume=233 |issue= 1 |pages= 48–54 |year= 1995 |pmid= 7588773 |doi=10.1111/j.1432-1033.1995.048_1.x |doi-access=free }} *{{cite journal |vauthors=Garcia-Caballero T, Dominguez F, Roson E, etal |title=Distribution of prothymosin alpha in rat and human adrenal cortex. |journal=Anat. Rec. |volume=239 |issue= 1 |pages= 88–94 |year= 1994 |pmid= 7913591 |doi= 10.1002/ar.1092390110 |s2cid=38666222 }} *{{cite journal |vauthors=Szabo P, Panneerselvam C, Clinton M, etal |title=Prothymosin alpha gene in humans: organization of its promoter region and localization to chromosome 2. |journal=Hum. Genet. |volume=90 |issue= 6 |pages= 629–34 |year= 1993 |pmid= 7916742 |doi=10.1007/BF00202480 |s2cid=6902846 }} *{{cite journal |vauthors=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1–2 |pages= 171–4 |year= 1994 |pmid= 8125298 |doi=10.1016/0378-1119(94)90802-8 }} *{{cite journal |vauthors=Tsitsiloni OE, Stiakakis J, Koutselinis A, etal |title=Expression of alpha-thymosins in human tissues in normal and abnormal growth. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=90 |issue= 20 |pages= 9504–7 |year= 1993 |pmid= 8415730 |doi=10.1073/pnas.90.20.9504 | pmc=47597 |bibcode=1993PNAS...90.9504T |doi-access=free }} *{{cite journal |vauthors=Sburlati AR, De La Rosa A, Batey DW, etal |title=Phosphorylation of human and bovine prothymosin alpha in vivo. |journal=Biochemistry |volume=32 |issue= 17 |pages= 4587–96 |year= 1993 |pmid= 8485135 |doi=10.1021/bi00068a015 }} *{{cite journal |author1=Rubtsov IuP |author2=Vartapetian AB |title=[New intronless members of human prothymosin alpha genes] |journal=Mol. Biol. (Mosk.) |volume=29 |issue= 6 |pages= 1320–5 |year= 1996 |pmid= 8592501 }} {{refend}}
{{Hormones}}
{{DEFAULTSORT:Thymosin alpha1}} Category:Hormones of the thymus gland Category:Peptides