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Statements

Subject Item
n2:DB00069
rdf:type
n5:Drug
n5: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.
n5:generalReferences
# 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":http://www.ncbi.nlm.nih.gov/pubmed/8836913 # http://www.google.com/patents/EP0422697A1?cl=en # Lexicomp Online (2014). Interferon Alfacon-1. Available at: http://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/7093#f_pharmacology-and-pharmacokinetics [Accessed 12 Nov. 2014].
n5:group
approved
n5:halfLife
The terminal half-life following subcutaneous dosing was 1.3 hours in golden Syrian hamsters and 3.4 hours in rhesus monkeys.
n5:indication
For the treatment of hairy cell leukemia, malignant melanoma, and AIDS-related Kaposi's sarcoma
owl:sameAs
n16:DB00069 n22:DB00069
dcterms:title
Interferon alfacon-1
adms:identifier
n12:PA164749376 n14:DB00069 n20:0187-2007-06 n21:J00207
n5:mechanismOfAction
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. 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.
n5:packager
n6:271B4336-363D-11E5-9242-09173F13E4C5 n6:271B4334-363D-11E5-9242-09173F13E4C5 n6:271B4335-363D-11E5-9242-09173F13E4C5 n6:271B4333-363D-11E5-9242-09173F13E4C5
n5:routeOfElimination
Due predominantly to catabolism and excretion by the kidneys.
n5:synonym
methionyl interferon consensus methionyl-interferon-consensus Recombinant Consensus Interferon IFN Alfacon-1 CIFN Recombinant methionyl human consensus interferon rCon-IFN Interferon Consensus, Methionyl consensus interferon
n5: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.
n3:hasAHFSCode
n4:10-00-00
n5:synthesisReference
Lin Wang, " NEW TYPE OF CONSENSUS INTERFERON AND PREPARATION METHOD THEREOF." U.S. Patent US20100266536, issued October 21, 2010.
n7:hasConcept
n8:M0144715
foaf:page
n10:infergen.htm n18:interferon-alfacon-1.html
n5:Molecular-Formula
n13:271B433D-363D-11E5-9242-09173F13E4C5
n5:Molecular-Weight
n13:271B433C-363D-11E5-9242-09173F13E4C5
n3:hasATCCode
n23:L03AB09
n5:absorption
Subcutaneous bioavailability averages 99% in golden Syrian hamsters and 83% to 104% in rhesus monkeys.
n5:affectedOrganism
Humans and other mammals
n5:casRegistryNumber
118390-30-0
n5:category
n5:clearance
Clearance, averaging 1.99 mL/minute/kg in golden Syrian hamsters and 0.71 to 0.92 mL/minute/kg in rhesus monkeys
n5:containedIn
n17:271B4338-363D-11E5-9242-09173F13E4C5 n17:271B4337-363D-11E5-9242-09173F13E4C5
n5:Hydrophobicity
n13:271B433A-363D-11E5-9242-09173F13E4C5
n5:Isoelectric-Point
n13:271B433B-363D-11E5-9242-09173F13E4C5
n5:Melting-Point
n13:271B4339-363D-11E5-9242-09173F13E4C5