Identification
Name Interferon alfacon-1
Accession Number DB00069 (BIOD00062, BTD00062)
Type biotech
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.
Structure
Categories (*)
Molecular Weight 19343.0000
Groups approved
Monoisotopic Weight Not Available
Pharmacology
Indication For the treatment of hairy cell leukemia, malignant melanoma, and AIDS-related Kaposi's sarcoma
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.
Protein binding Not Available
Biotransformation 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.
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
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Interferon-alpha/beta receptor alpha chain
Name Interferon-alpha/beta receptor alpha chain
Gene Name IFNAR1
Pharmacological action yes
Actions binder
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
  • 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
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 1.8511
Interferon-alpha/beta receptor beta chain
Name Interferon-alpha/beta receptor beta chain
Gene Name IFNAR2
Pharmacological action yes
Actions binder
References
  • 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
  • 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
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 1.8511