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Identification
Name Interferon alfacon-1
Accession Number DB00069 (BIOD00062, BTD00062)
Type biotech
Groups approved
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 structure Db00069
Display: 3D Structure
Protein chemical formula C860H1353N227O255S9
Protein average weight 19343.0000
Sequences
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
Salts Not Available
Brand names
Name Company
Advaferon
Infergen InterMune Inc.
Brand mixtures Not Available
Categories
  • Antineoplastic Agents
  • Immunomodulatory Agents
  • Antiviral Agents
CAS number 118390-30-0
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication For the treatment of hairy cell leukemia, malignant melanoma, and AIDS-related Kaposi's sarcoma
Pharmacodynamics Upregulates 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 action Interferon 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.
Absorption Subcutaneous bioavailability averages 99% in golden Syrian hamsters and 83% to 104% in rhesus monkeys.
Volume of distribution Not Available
Protein binding Not Available
Metabolism Not Available
Route of elimination Clearance, averaging 1.99 mL/minute/kg in golden Syrian hamsters and 0.71 to 0.92 mL/minute/kg in rhesus monkeys, was due predominantly to catabolism and excretion by the kidneys.
Half life The terminal half-life following subcutaneous dosing was 1.3 hours in golden Syrian hamsters and 3.4 hours in rhesus monkeys.
Clearance Not Available
Toxicity Reproductive 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
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers
Dosage forms
Form Route Strength
Solution Subcutaneous
Prices
Unit description Cost Unit
Infergen 15 mcg/0.5ml Injectable 0.5ml Vial 134.24 USD vial
Infergen 9 mcg/0.3 ml vial 129.08 USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State liquid
Experimental Properties
Property Value Source
melting point 61 °C Beldarrain, A. et al., Biochemistry 38:7865-7873 (1999)
hydrophobicity -0.336 Not Available
isoelectric point 5.99 Not Available
References
Synthesis Reference Not Available
General Reference
  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
External Links
Resource Link
Genbank J00207 Link_out
PharmGKB PA164749376 Link_out
Drug Product Database 2239832 Link_out
RxList http://www.rxlist.com/cgi/generic2/infergen.htm Link_out
Drugs.com http://www.drugs.com/cdi/interferon-alfacon-1.html Link_out
ATC Codes
  • L03AB09
AHFS Codes
  • 10:00.00
PDB Entries
FDA label show (732 KB)
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Interferon-alpha/beta receptor alpha chain

Pharmacological action: yes
Actions: binder

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

Organism class: human
UniProt ID: P17181 Link_out
Gene: IFNAR1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  3. Yasuda S, Miyata K: [Interferon alfacon-1 (Advaferon): a novel synthetic interferon for the treatment of hepatitis C, its pharmacological and clinical profile] Nippon Yakurigaku Zasshi. 2002 Dec;120(6):421-6. Pubmed
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Interferon-alpha/beta receptor beta chain

Pharmacological action: yes
Actions: binder

Receptor for interferons alpha and beta. Isoform 1 and isoform 3 are directly involved in signal transduction due to their interaction with the TYR kinase, JAK1. Isoform 1 also interacts with the transcriptional factors, STAT1 and STAT2. Both forms are potent inhibitors of type I IFN activity

Organism class: human
UniProt ID: P48551 Link_out
Gene: IFNAR2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  2. Yasuda S, Miyata K: [Interferon alfacon-1 (Advaferon): a novel synthetic interferon for the treatment of hepatitis C, its pharmacological and clinical profile] Nippon Yakurigaku Zasshi. 2002 Dec;120(6):421-6. Pubmed
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on September 29, 2010 14:34