You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NamePeginterferon alfa-2a
Accession NumberDB00008  (BTD00043, BIOD00043)
TypeBiotech
GroupsApproved, Investigational
Description

Human interferon 2a, is a covalent conjugate of recombinant alfa-2a interferon with a single branched bis-monomethoxy polyethylene glycol (PEG) chain. The PEG moiety is linked at a single site to the interferon alfa moiety via a stable amide bond to lysine. Peginterferon alfa-2a has an approximate molecular weight of 60,000 daltons. Interferon alfa-2a is produced using recombinant DNA technology in which a cloned human leukocyte interferon gene is inserted into and expressed in Escherichia coli. The resultant protein is 165 amino acids. The PEG strand protects the molecule in vivo from proteolytic breakdown, substantially increases its in vivo half-life, and reduces immunogenicity by wrapping around and physically hindering access to the protein portion of the molecule.

Protein structureDb00008
Related Articles
Protein chemical formulaNot Available
Protein average weight60000.0 Da
Sequences
>Peginterferon alfa-2a sequence
CDLPQTHSLGSRRTLMLLAQMRRISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMI
QQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVR
KYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE
Download FASTA Format
SynonymsNot Available
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Pegasysinjection, solution180 ug/mLsubcutaneousGenentech, Inc.2002-10-16Not applicableUs
Pegasyssolution180 mcgsubcutaneousHoffmann La Roche Limited2003-08-14Not applicableCanada
Pegasyssolution180 mcgsubcutaneousHoffmann La Roche Limited2003-08-14Not applicableCanada
Pegasysinjection, solution180 ug/.5mLsubcutaneousGenentech, Inc.2011-11-01Not applicableUs
Pegasysinjection, solution135 ug/.5mLsubcutaneousGenentech, Inc.2011-11-01Not applicableUs
Pegasysinjection, solution180 ug/.5mLsubcutaneousGenentech, Inc.2011-03-29Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixtures
NameLabellerIngredients
Pegasys RbvHoffmann La Roche Limited
SaltsNot Available
Categories
UNIIQ46947FE7K
CAS number198153-51-4
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available
Pharmacology
IndicationFor treatment of hairy cell leukemia, malignant melanoma, and AIDS-related Kaposi's sarcoma.
PharmacodynamicsUpregulates the expression of MHC I proteins, allowing for increased presentation of peptides derived from viral antigens. This enhances the activation of CD8+ T cells that are the precursors for cytotoxic T lymphocytes (CTLs) and makes the macrophage a better target for CTL-mediated killing. Interferon alpha also induce the synthesis of several key antiviral mediators, including 2'-5' oligoadenylate synthetase (2'-5' A synthetase) and protein kinase R.
Mechanism of actionInterferon alpha binds to type I interferon receptors (IFNAR1 and IFNAR2c) which, upon dimerization, activate two Jak (Janus kinase) tyrosine kinases (Jak1 and Tyk2). These transphosphorylate themselves and phosphorylate the receptors. The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of transcription) which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins. Interferon alpha binds less stably to type I interferon receptors than interferon beta.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeTerminal half life is 80 hours (range 50 to 140 hours).
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Injection, solutionsubcutaneous135 ug/.5mL
Injection, solutionsubcutaneous180 ug/mL
Injection, solutionsubcutaneous180 ug/.5mL
Solutionsubcutaneous180 mcg
Solution; tabletoral; subcutaneous
Prices
Unit descriptionCostUnit
Pegasys (1 Kit = Four 180 mcg/ml Vials Prefilled Syringes) Box2634.53USD box
Pegasys 180 mcg/0.5 ml conv.pk2533.2USD each
Pegasys 180 mcg/ml vial642.64USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2172664 No2000-10-032016-03-26Canada
CA2203480 No2009-06-302017-04-23Canada
Properties
StateLiquid
Experimental Properties
PropertyValueSource
melting point61 °CBeldarrain, A. et al., Biochemistry 38:7865-7873 (1999)
isoelectric point5.99Not Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesL03AB61L03AB11
AHFS Codes
  • 08:18.20
PDB Entries
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AldesleukinThe risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Aldesleukin.
AminophyllineThe metabolism of Aminophylline can be decreased when combined with Peginterferon alfa-2a.
ClozapineThe risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Clozapine.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Peginterferon alfa-2a.
MethadoneThe serum concentration of Methadone can be increased when it is combined with Peginterferon alfa-2a.
PegloticaseThe therapeutic efficacy of Peginterferon alfa-2a can be decreased when used in combination with Pegloticase.
RibavirinThe risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Ribavirin.
TelbivudineThe risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Telbivudine.
TheophyllineThe metabolism of Theophylline can be decreased when combined with Peginterferon alfa-2a.
TizanidineThe serum concentration of Tizanidine can be increased when it is combined with Peginterferon alfa-2a.
ZidovudineThe risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Zidovudine.
Food Interactions
  • Recommended adequate hydration.

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Type i interferon receptor activity
Specific Function:
Associates with IFNAR1 to form the type I interferon receptor. Receptor for interferons alpha and beta. Involved in IFN-mediated STAT1, STAT2 and STAT3 activation. Isoform 1 and isoform 2 are directly involved in signal transduction due to their association with the TYR kinase, JAK1. Isoform 3 is a potent inhibitor of type I IFN receptor activity.
Gene Name:
IFNAR2
Uniprot ID:
P48551
Molecular Weight:
57758.24 Da
References
  1. Dhalluin C, Ross A, Huber W, Gerber P, Brugger D, Gsell B, Senn H: Structural, kinetic, and thermodynamic analysis of the binding of the 40 kDa PEG-interferon-alpha2a and its individual positional isomers to the extracellular domain of the receptor IFNAR2. Bioconjug Chem. 2005 May-Jun;16(3):518-27. [PubMed:15898717 ]
  2. Yano H, Ogasawara S, Momosaki S, Akiba J, Kojiro S, Fukahori S, Ishizaki H, Kuratomi K, Basaki Y, Oie S, Kuwano M, Kojiro M: Growth inhibitory effects of pegylated IFN alpha-2b on human liver cancer cells in vitro and in vivo. Liver Int. 2006 Oct;26(8):964-75. [PubMed:16953837 ]
  3. Ishii K, Shinohara M, Sawa M, Kogame M, Higami K, Sano M, Morita T, Sumino Y: Interferon alpha receptor 2 expression by peripheral blood monocytes in patients with a high viral load of hepatitis C virus genotype 1 showing substitution of amino Acid 70 in the core region. Intervirology. 2010;53(2):105-10. doi: 10.1159/000264200. Epub 2009 Dec 3. [PubMed:19955815 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Type i interferon receptor activity
Specific Function:
Associates with IFNAR2 to form the type I interferon receptor. Receptor for interferons alpha and beta. Binding to type I IFNs triggers tyrosine phosphorylation of a number of proteins including JAKs, TYK2, STAT proteins and IFNR alpha- and beta-subunits themselves. Can also transduce IFNB signals without the help of IFNAR2, and not activating the Jak-STAT pathway.
Gene Name:
IFNAR1
Uniprot ID:
P17181
Molecular Weight:
63524.81 Da
References
  1. Dhalluin C, Ross A, Huber W, Gerber P, Brugger D, Gsell B, Senn H: Structural, kinetic, and thermodynamic analysis of the binding of the 40 kDa PEG-interferon-alpha2a and its individual positional isomers to the extracellular domain of the receptor IFNAR2. Bioconjug Chem. 2005 May-Jun;16(3):518-27. [PubMed:15898717 ]
  2. Yano H, Ogasawara S, Momosaki S, Akiba J, Kojiro S, Fukahori S, Ishizaki H, Kuratomi K, Basaki Y, Oie S, Kuwano M, Kojiro M: Growth inhibitory effects of pegylated IFN alpha-2b on human liver cancer cells in vitro and in vivo. Liver Int. 2006 Oct;26(8):964-75. [PubMed:16953837 ]
  3. Ishii K, Shinohara M, Sawa M, Kogame M, Higami K, Sano M, Morita T, Sumino Y: Interferon alpha receptor 2 expression by peripheral blood monocytes in patients with a high viral load of hepatitis C virus genotype 1 showing substitution of amino Acid 70 in the core region. Intervirology. 2010;53(2):105-10. doi: 10.1159/000264200. Epub 2009 Dec 3. [PubMed:19955815 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23