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Identification
NameInterferon alfacon-1
Accession NumberDB00069  (BTD00062, BIOD00062)
TypeBiotech
GroupsApproved
Description

Interferon alfacon-1 is a recombinant non-naturally occurring type-I interferon. The 166-amino acid sequence of Interferon alfacon-1 was derived by scanning the sequences of several natural interferon alpha subtypes and assigning the most frequently observed amino acid in each corresponding position. Four additional amino acid changes were made to facilitate the molecular construction, and a corresponding synthetic DNA sequence was constructed using chemical synthesis methodology. Interferon alfacon-1 differs from interferon alfa-2b at 20/166 amino acids (88% homology), and comparison with interferon-beta shows identity at over 30% of the amino acid positions. Interferon alfacon-1 is produced in Escherichia coli (E. coli) cells that have been genetically altered by insertion of a synthetically constructed sequence that codes for Interferon alfacon-1. Prior to final purification, Interferon alfacon-1 is allowed to oxidize to its native state, and its final purity is achieved by sequential passage over a series of chromatography columns. This protein has a molecular weight of 19,434 daltons.

Protein structureDb00069
Related Articles
Protein chemical formulaC860H1353N227O255S9
Protein average weight19343.0 Da
Sequences
> Interferon alfacon-1
MCDLPQTHSLGNRRALILLAQMRRISPFSCLKDRHDFGFPQEEFDGNQFQKAQAISVLHE
MIQQTFNLFSTKDSSAAWDESLLEKFYTELYQQLNDLEACVIQEVGVEETPLMNVDSILA
VKKYFQRITLYLTEKKYSPCAWEVVRAEIMRSFSLSTNLQERLRRKE
Download FASTA Format
Synonyms
CIFN
consensus interferon
IFN Alfacon-1
Interferon Consensus, Methionyl
methionyl interferon consensus
methionyl-interferon-consensus
rCon-IFN
Recombinant Consensus Interferon
Recombinant methionyl human consensus interferon
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Infergensolution0.03 mgsubcutaneousThree Rivers Pharmaceuticals Llc1999-07-122012-10-31Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AdvaferonNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII56588OP40D
CAS number118390-30-0
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 the 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. The resulting actions include gene transcription, inhibition of cellular growth, alteration of the state of cellular differentiation, interference with oncogene expression, alteration of cell surface antigen expression, increasing phagocytic activity of macrophages, and augmentation of the cytotoxicity of lymphocytes for target cells.
Related Articles
AbsorptionSubcutaneous bioavailability averages 99% in golden Syrian hamsters and 83% to 104% in rhesus monkeys.
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationDue predominantly to catabolism and excretion by the kidneys.
Half lifeThe terminal half-life following subcutaneous dosing was 1.3 hours in golden Syrian hamsters and 3.4 hours in rhesus monkeys.
Clearance

Clearance, averaging 1.99 mL/minute/kg in golden Syrian hamsters and 0.71 to 0.92 mL/minute/kg in rhesus monkeys

ToxicityReproductive toxicity studies in pregnant rhesus monkeys and golden Syrian hamsters demonstrated an increase in fetal loss in hamsters treated with Interferon alfacon-1 at doses of > 150 mcg/kg/day, and in rhesus monkeys at doses of 3 and 10 mcg/kg/day. The Interferon alfacon-1 toxicity profile described is consistent with the known toxicity profile of other alpha interferons.
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
Solutionsubcutaneous0.03 mg
Prices
Unit descriptionCostUnit
Infergen 15 mcg/0.5ml Injectable 0.5ml Vial134.24USD vial
Infergen 9 mcg/0.3 ml vial129.08USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateLiquid
Experimental Properties
PropertyValueSource
melting point61 °CBeldarrain, A. et al., Biochemistry 38:7865-7873 (1999)
hydrophobicity-0.336Not Available
isoelectric point5.99Not Available
References
Synthesis Reference

Lin Wang, " NEW TYPE OF CONSENSUS INTERFERON AND PREPARATION METHOD THEREOF." U.S. Patent US20100266536, issued October 21, 2010.

US20100266536
General References
  1. Blatt LM, Davis JM, Klein SB, Taylor MW: The biologic activity and molecular characterization of a novel synthetic interferon-alpha species, consensus interferon. J Interferon Cytokine Res. 1996 Jul;16(7):489-99. [PubMed:8836913 ]
  2. Link [Link]
External Links
ATC CodesL03AB09
AHFS Codes
  • 10:00.00
PDB Entries
FDA labelDownload (732 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AldesleukinThe risk or severity of adverse effects can be increased when Interferon alfacon-1 is combined with Aldesleukin.
ClozapineThe risk or severity of adverse effects can be increased when Interferon alfacon-1 is combined with Clozapine.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Interferon alfacon-1.
MethadoneThe serum concentration of Methadone can be increased when it is combined with Interferon alfacon-1.
RibavirinThe risk or severity of adverse effects can be increased when Interferon alfacon-1 is combined with Ribavirin.
TheophyllineThe metabolism of Theophylline can be decreased when combined with Interferon alfacon-1.
ZidovudineThe risk or severity of adverse effects can be increased when Interferon alfacon-1 is combined with Zidovudine.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
binder
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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Yasuda S, Miyata K: [Interferon alfacon-1 (Advaferon): a novel synthetic interferon for the treatment of hepatitis C, its pharmacological and clinical profile]. Nihon Yakurigaku Zasshi. 2002 Dec;120(6):421-6. [PubMed:12528473 ]
  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
binder
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. Blatt LM, Davis JM, Klein SB, Taylor MW: The biologic activity and molecular characterization of a novel synthetic interferon-alpha species, consensus interferon. J Interferon Cytokine Res. 1996 Jul;16(7):489-99. [PubMed:8836913 ]
  2. Yasuda S, Miyata K: [Interferon alfacon-1 (Advaferon): a novel synthetic interferon for the treatment of hepatitis C, its pharmacological and clinical profile]. Nihon Yakurigaku Zasshi. 2002 Dec;120(6):421-6. [PubMed:12528473 ]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23