Thymalfasin

Identification

Name
Thymalfasin
Accession Number
DB04900
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Interleukin-based products
Description

Thymalfasin is a chemically synthesized version of thymosin alpha 1 that is identical to human thymosin alpha 1. Thymosin alpha 1 is an acetylated polypeptide. Thymosin alpha 1 is now approved in 35 developing countries for the treatment of Hepatitis B and C. It is also used to boost the immune response in the treatment of other diseases.

Protein structure
Db04900
Protein chemical formula
C129H215N33O55
Protein average weight
3108.2755 Da
Sequences
>Thymalfasin
SDAAVDTSSEITTKDLKEKKEVVEEAEN
Download FASTA Format
Synonyms
  • Thymosin alpha1 (human)
International/Other Brands
Zadaxin
Categories
UNII
W0B22ISQ1C
CAS number
62304-98-7

Pharmacology

Indication

Indicated as an adjuvant for influenza vaccine in elderly patients and as an adjuvant for both influenza and hepatitis B vaccines in chronic hemodialysis patients who failed to achieve adequate antibody titers from previous immunization.

Structured Indications
Not Available
Pharmacodynamics

Thymalfasin is a 28-amino acid polypeptide produced synthetically but originally isolated from thymosin fraction 5, a bovine thymus extract containing a number of immunologically active peptides. In vitro studies have shown that Thymalfasin can influence T-cell production and maturation, stimulate production of Th1 cytokines such as interferon-gamma and interleukin-2, and activate natural killer cell-mediated cytotoxicity.

Mechanism of action

The mechanism of action of thymalfasin is not completely understood but is thought to be related to its immunomodulating activities, centered primarily around augmentation of T-cell function. In various in vitro assays, thymosin alpha 1 has been shown to promote T-cell differentiation and maturation; for example, CD4+, CD8+, and CD3+ cells have all been shown to be increased. Thymosin alpha 1 has also been shown to increase production of IFN-g, IL-2, IL-3, and expression of IL-2 receptor following activation by mitogens or antigens, increase NK cell activity, increase production of migratory inhibitory factor (MIF), and increase antibody response to T-cell dependent antigens. Thymosin alpha 1 has also been shown to antagonize dexamethasone-induced apoptosis of thymocytes in vitro. In vivo administration of thymosin alpha 1 to animals immunosuppressed by chemotherapy, tumor burden, or irradiation showed that thymosin alpha 1 protects against cytotoxic damage to bone marrow, tumor progression and opportunistic infections, thereby increasing survival time and number of survivors. Many of the in vitro and in vivo effects of thymosin alpha 1 have been interpreted as influences on either differentiation of pluripotent stem cells to thymocytes or activation of thymocytes into activated T-cells. Thymalfasin also has been shown in vitro to upregulate expression of toll like receptors (TLR) including TLR2 and TLR9 in mouse and human dendritic cells, as well as activate NF-kB and JNK/P38/AP1 pathways. Thymalfasin's activation of dendritic cells provides another possible pathway explaining thymalfasin's immunomodulatory and antiviral effects.

Absorption

Rapidly absorbed with peak serum levels achieved at approximately 2 hours.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

Approximately 2 hours. There is no evidence of accumulation following multiple subcutaneous doses.

Clearance
Not Available
Toxicity

There are no reported instances of deliberate or accidental overdosage in humans. Animal toxicology studies have shown no adverse reactions in single doses up to 20 mg/kg and in repeated doses up to 6 mg/kg/day for 13 weeks, which were the highest doses studied. The highest single dose tested in animals represents 800-times the clinical dose.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Thymalfasin.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Thymalfasin.Experimental
BevacizumabBevacizumab may increase the cardiotoxic activities of Thymalfasin.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Thymalfasin.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Thymalfasin.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Thymalfasin.Experimental
DeslanosideDeslanoside may decrease the cardiotoxic activities of Thymalfasin.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Thymalfasin.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Thymalfasin.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Thymalfasin.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Thymalfasin.Approved, Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Thymalfasin.Experimental
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Thymalfasin.Experimental
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Thymalfasin.Experimental
OleandrinOleandrin may decrease the cardiotoxic activities of Thymalfasin.Experimental, Investigational
OuabainOuabain may decrease the cardiotoxic activities of Thymalfasin.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Thymalfasin.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Thymalfasin.Experimental
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Thymalfasin.Experimental
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Thymalfasin.Approved, Investigational
Food Interactions
Not Available

References

Synthesis Reference

Christian Birr, Ulrich Stollenwerk, "Method of preparing thymosin alpha 1 and derivatives thereof." U.S. Patent US4466918, issued April, 1979.

US4466918
General References
  1. Chien RN, Liaw YF: Thymalfasin for the treatment of chronic hepatitis B. Expert Rev Anti Infect Ther. 2004 Feb;2(1):9-16. [PubMed:15482167]
  2. Sjogren MH: Thymalfasin: an immune system enhancer for the treatment of liver disease. J Gastroenterol Hepatol. 2004 Dec;19 Suppl 6:S69-72. [PubMed:15546253]
  3. Liaw YF: Thymalfasin (thymosin-alpha 1) therapy in patients with chronic hepatitis B. J Gastroenterol Hepatol. 2004 Dec;19 Suppl 6:S73-5. [PubMed:15546254]
  4. Sjogren MH: Thymalfasin: an immune system enhancer for the treatment of liver disease. J Gastroenterol Hepatol. 2004 Dec;19(12):S69-72. [PubMed:15641207]
  5. Liaw YF: Thymalfasin (thymosin-alpha 1) therapy in patients with chronic hepatitis B. J Gastroenterol Hepatol. 2004 Dec;19(12):S73-5. [PubMed:15641208]
  6. Vemuri S: Comparison of assays for determination of peptide content for lyophilized thymalfasin. J Pept Res. 2005 Apr;65(4):433-9. [PubMed:15813890]
  7. Rustgi VK: Thymalfasin for the treatment of chronic hepatitis C infection. Expert Rev Anti Infect Ther. 2005 Dec;3(6):885-92. [PubMed:16307501]
  8. Rustgi VK: Thymalfasin for the treatment of chronic hepatitis C infection. Ann N Y Acad Sci. 2007 Sep;1112:357-67. Epub 2007 Jun 28. [PubMed:17600289]
  9. Gramenzi A, Cursaro C, Andreone P, Bernardi M: Thymalfasin: clinical pharmacology and antiviral applications. BioDrugs. 1998 Jun;9(6):477-86. [PubMed:18020580]
  10. Pierluigi B, D'Angelo C, Fallarino F, Moretti S, Zelante T, Bozza S, De Luca A, Bistoni F, Garaci E, Romani L: Thymosin alpha1: the regulator of regulators? Ann N Y Acad Sci. 2010 Apr;1194:1-5. doi: 10.1111/j.1749-6632.2010.05465.x. [PubMed:20536444]
External Links
PubChem Substance
46504578
ChEMBL
CHEMBL2103979
PharmGKB
PA164748387
RxList
RxList Drug Page

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Not Yet RecruitingPreventionPancreatitis,Acute Necrotizing1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
1, 2CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection1
1, 2CompletedTreatmentHepatitis B,Chronic1
1, 2Not Yet RecruitingTreatmentEGFR Mutation Positive Non Small Cell Lung Cancer1
1, 2Unknown StatusTreatmentHaematological Malignancies1
2CompletedSupportive CareEnd Stage Renal Disease (ESRD)1
2CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection2
2CompletedTreatmentHepatocellular,Carcinoma1
2CompletedTreatmentMalignant Melanoma1
2Not Yet RecruitingTreatmentColorectal Cancers / Metastatic Colorectal Cancers / Thymalfasin1
2Not Yet RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2Not Yet RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Metastatic Non-Small Cell Lung Cancer / Radiotherapy / Thymalfasin1
2Not Yet RecruitingTreatmentLung Cancer Small Cell Lung Cancer (SCLC) / Radiotherapy / Thymalfasin1
2RecruitingTreatmentAdenocarcinoma of the Lung1
2RecruitingTreatmentEsophageal Cancers / Metastatic Esophageal Cancer / Stereotactic Body Radiation Therapy / Thymalfasin1
3CompletedTreatmentChronic Hepatitis C Infection / Hepatitis C, Chronic1
3CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection1
3RecruitingTreatmentSepsis1
4Not Yet RecruitingTreatmentCurable Hepatitis B Virus-Related Hepatocellular Carcinoma1
4RecruitingTreatmentLiver Cirrhosis2
4RecruitingTreatmentSepsis1
Not AvailableCompletedTreatmentSevere Sepsis1
Not AvailableNot Yet RecruitingTreatmentHepatic Failure1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Drug created on October 21, 2007 16:23 / Updated on November 06, 2017 06:45