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
- Protein chemical formula
- C860H1353N227O255S9
- Protein average weight
- 19343.0 Da
- Sequences
> Interferon alfacon-1 MCDLPQTHSLGNRRALILLAQMRRISPFSCLKDRHDFGFPQEEFDGNQFQKAQAISVLHE MIQQTFNLFSTKDSSAAWDESLLEKFYTELYQQLNDLEACVIQEVGVEETPLMNVDSILA VKKYFQRITLYLTEKKYSPCAWEVVRAEIMRSFSLSTNLQERLRRKE
Download FASTA Format- Synonyms
- IFN Alfacon-1
- IFN-Con1
- Interferon alfacon-1
- Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Infergen Injection 0.03 mg/1mL Subcutaneous Valeant Pharmaceuticals, Inc. 1997-10-01 2017-12-31 US Infergen Injection 0.03 mg/1mL Subcutaneous Kadmon Pharmaceuticals 1997-10-06 2014-03-31 US Infergen Injection 0.03 mg/1mL Subcutaneous Kadmon Pharmaceuticals 1997-10-06 2014-03-31 US Infergen Solution 0.03 mg Subcutaneous Three Rivers Pharmaceuticals Llc 1999-07-12 2012-10-31 Canada - International/Other Brands
- Advaferon / Infergen
- Categories
- Adjuvants, Immunologic
- Alfa Interferons
- Amino Acids, Peptides, and Proteins
- Anti-Infective Agents
- Antineoplastic and Immunomodulating Agents
- Antiviral Agents
- Biological Factors
- Cytokines
- Immunosuppressive Agents
- Intercellular Signaling Peptides and Proteins
- Interferon alpha
- Interferon Type I
- Interferons
- Myelosuppressive Agents
- Peptides
- Proteins
- UNII
- 56588OP40D
- CAS number
- 118390-30-0
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. 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.
Target Actions Organism AInterferon alpha/beta receptor 1 binderHumans AInterferon alpha/beta receptor 2 binderHumans - 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
Drug Interaction (R)-warfarin The risk or severity of bleeding can be increased when (R)-warfarin is combined with Interferon alfacon-1. (S)-Warfarin The risk or severity of bleeding can be increased when (S)-Warfarin is combined with Interferon alfacon-1. 2-Methoxyethanol The risk or severity of adverse effects can be increased when Interferon alfacon-1 is combined with 2-Methoxyethanol. 3-isobutyl-1-methyl-7H-xanthine The metabolism of 3-isobutyl-1-methyl-7H-xanthine can be decreased when combined with Interferon alfacon-1. 4-hydroxycoumarin The risk or severity of bleeding can be increased when 4-hydroxycoumarin is combined with Interferon alfacon-1. 6-O-benzylguanine The metabolism of 6-O-benzylguanine can be decreased when combined with Interferon alfacon-1. 7-Deazaguanine The metabolism of 7-Deazaguanine can be decreased when combined with Interferon alfacon-1. 7,9-Dimethylguanine The metabolism of 7,9-Dimethylguanine can be decreased when combined with Interferon alfacon-1. 8-azaguanine The metabolism of 8-azaguanine can be decreased when combined with Interferon alfacon-1. 8-chlorotheophylline The metabolism of 8-chlorotheophylline can be decreased when combined with Interferon alfacon-1. - 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
- 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]
- 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
- Wikipedia
- Interferon_alfacon-1
- ATC Codes
- L03AB09 — Interferon alfacon-1
- FDA label
- Download (732 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 1, 2 Unknown Status Treatment Flu caused by Influenza 1 3 Completed Treatment Chronic Hepatitis C Virus (HCV) Infection 1 3 Completed Treatment Hepatitis C Viral Infection 1 4 Completed Treatment Hepatitis C Viral Infection 2 4 Terminated Treatment Hepatitis C Viral Infection 1 Not Available Withdrawn Not Available Hepatitis C Viral Infection 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Amgen Inc.
- InterMune Inc.
- Three Rivers Pharmaceuticals LLC
- Valeant Ltd.
- Dosage forms
Form Route Strength Injection Subcutaneous 0.03 mg/1mL Solution Subcutaneous 0.03 mg - Prices
Unit description Cost Unit Infergen 15 mcg/0.5ml Injectable 0.5ml Vial 134.24USD vial Infergen 9 mcg/0.3 ml vial 129.08USD vial DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
Property Value Source melting point (°C) 61 °C Beldarrain, A. et al., Biochemistry 38:7865-7873 (1999) hydrophobicity -0.336 Not Available isoelectric point 5.99 Not 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
- Humans
- 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
- 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]
- 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]
- 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]
- 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
- Humans
- 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
- 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]
- 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]
- 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 January 02, 2019 21:22