Interferon alfacon-1

Identification

Name
Interferon alfacon-1
Accession Number
DB00069  (BTD00062, BIOD00062)
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Interferons
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
Protein chemical formula
C860H1353N227O255S9
Protein average weight
19343.0 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
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
InfergenSolution0.03 mgSubcutaneousThree Rivers Pharmaceuticals Llc1999-07-122012-10-31Canada
International/Other Brands
Advaferon
Categories
UNII
56588OP40D
CAS number
118390-30-0

Pharmacology

Indication

For the treatment of hairy cell leukemia, malignant melanoma, and AIDS-related Kaposi's sarcoma

Structured Indications
Not Available
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. 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.

TargetActionsOrganism
AInterferon alpha/beta receptor 1
binder
Human
AInterferon alpha/beta receptor 2
binder
Human
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

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

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

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
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AldesleukinThe risk or severity of adverse effects can be increased when Interferon alfacon-1 is combined with Aldesleukin.Approved
Ambroxol acefyllinateThe metabolism of Ambroxol acefyllinate can be decreased when combined with Interferon alfacon-1.Experimental, Investigational
AminophyllineThe metabolism of Aminophylline can be decreased when combined with Interferon alfacon-1.Approved
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Interferon alfacon-1.Investigational
ClozapineThe risk or severity of adverse effects can be increased when Interferon alfacon-1 is combined with Clozapine.Approved
DyphyllineThe metabolism of Dyphylline can be decreased when combined with Interferon alfacon-1.Approved
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Interferon alfacon-1.Investigational, Withdrawn
MethadoneThe serum concentration of Methadone can be increased when it is combined with Interferon alfacon-1.Approved
RibavirinThe risk or severity of adverse effects can be increased when Interferon alfacon-1 is combined with Ribavirin.Approved
TheophyllineThe metabolism of Theophylline can be decreased when combined with Interferon alfacon-1.Approved
ZidovudineThe risk or severity of adverse effects can be increased when Interferon alfacon-1 is combined with Zidovudine.Approved
Food Interactions
Not 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
Genbank
J00207
PubChem Substance
46505985
ChEMBL
CHEMBL1201557
Therapeutic Targets Database
DAP001284
PharmGKB
PA164749376
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
ATC Codes
L03AB09 — Interferon alfacon-1
FDA label
Download (732 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2Unknown StatusTreatmentFlu caused by Influenza1
3CompletedTreatmentChronic Hepatitis C Infection1
3CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection1
4CompletedTreatmentChronic Hepatitis C Infection2
4TerminatedTreatmentChronic Hepatitis C Infection1
Not AvailableWithdrawnNot AvailableChronic Hepatitis C Infection1

Pharmacoeconomics

Manufacturers
Not 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.
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)61 °CBeldarrain, A. et al., Biochemistry 38:7865-7873 (1999)
hydrophobicity-0.336Not Available
isoelectric point5.99Not Available

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not 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 JA...
Gene Name
IFNAR1
Uniprot ID
P17181
Uniprot Name
Interferon alpha/beta receptor 1
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 direc...
Gene Name
IFNAR2
Uniprot ID
P48551
Uniprot Name
Interferon alpha/beta receptor 2
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]

Drug created on June 13, 2005 07:24 / Updated on November 06, 2017 06:43