Interferon alfacon-1

ID Pharmacology Interactions References Trials Economics Properties Taxonomy

Targets (2)

Targets (2)Biointeractions (2)

Identification

Name

Interferon alfacon-1

Accession Number

DB00069 (BTD00062, BIOD00062)

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

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

External IDs

Not Available

Product Ingredients

Not Available

Approved Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Infergen	Solution	0.03 mg	Subcutaneous	Three Rivers Pharmaceuticals Llc	1999-07-12	2012-10-31	Canada

Approved Generic Prescription Products

Not Available

Approved Over the Counter Products

Not Available

Unapproved/Other Products

Not Available

International Brands

Name	Company
Advaferon	Not Available

Brand mixtures

Not Available

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.

Target	Kind	Pharmacological action	Actions	Organism	UniProt ID
Interferon alpha/beta receptor 1	Protein	yes	binder	Human	P17181	details
Interferon alpha/beta receptor 2	Protein	yes	binder	Human	P48551	details

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	Drug group
Aldesleukin	The risk or severity of adverse effects can be increased when Interferon alfacon-1 is combined with Aldesleukin.	Approved
Ambroxol acefyllinate	The metabolism of Ambroxol acefyllinate can be decreased when combined with Interferon alfacon-1.	Experimental
Aminophylline	The metabolism of Aminophylline can be decreased when combined with Interferon alfacon-1.	Approved
Clozapine	The risk or severity of adverse effects can be increased when Interferon alfacon-1 is combined with Clozapine.	Approved
Dyphylline	The metabolism of Dyphylline can be decreased when combined with Interferon alfacon-1.	Approved
Metamizole	The risk or severity of adverse effects can be increased when Metamizole is combined with Interferon alfacon-1.	Withdrawn
Methadone	The serum concentration of Methadone can be increased when it is combined with Interferon alfacon-1.	Approved
Ribavirin	The risk or severity of adverse effects can be increased when Interferon alfacon-1 is combined with Ribavirin.	Approved
Theophylline	The metabolism of Theophylline can be decreased when combined with Interferon alfacon-1.	Approved
Zidovudine	The 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

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

Resource	Link
Genbank	J00207
PharmGKB	PA164749376
Drug Product Database	11856
RxList	http://www.rxlist.com/cgi/generic2/infergen.htm
Drugs.com	http://www.drugs.com/cdi/interferon-alfacon-1.html

ATC Codes

L03AB09

AHFS Codes

10:00.00

PDB Entries

1ITF

FDA label

Download (732 KB)

MSDS

Not Available

Clinical Trials

Phase	Status	Purpose	Conditions	Count
1, 2	Unknown Status	Treatment	Flu caused by Influenza	1
3	Completed	Treatment	Chronic Hepatitis C Infection	1
3	Completed	Treatment	Chronic Hepatitis C Virus (HCV) Infection	1
4	Completed	Treatment	Chronic Hepatitis C Infection	2
4	Terminated	Treatment	Chronic Hepatitis C Infection	1
Not Available	Withdrawn	Not Available	Chronic Hepatitis C Infection	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Dosage forms

Form	Route	Strength
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

Details

1. Interferon alpha/beta receptor 1

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 JAKs, TYK2, STAT proteins and IFNR alpha- and beta-subunits themselves. Can also transduce IFNB signals without the help of IFNAR2, and not activating the Jak-STAT pathway.
Gene Name:: IFNAR1
Uniprot ID:: P17181
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 ]

Details

2. Interferon alpha/beta receptor 2

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 directly involved in signal transduction due to their association with the TYR kinase, JAK1. Isoform 3 is a potent inhibitor of type I IFN receptor activity.
Gene Name:: IFNAR2
Uniprot ID:: P48551
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 August 17, 2016 12:23

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Targets

References

References