Identification

Name
Interferon alfa-n3
Accession Number
DB00018  (BTD00023, BIOD00023)
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Interferons
Description

Purified, natural (n is for natural) human interferon alpha proteins (consists of 3 forms or polymorphisms including 2a, 2b and 2c). 166 residues, some are glycosylated (MW range from 16 kD to 27 kD).

Protein structure
Db00018
Protein chemical formula
Not Available
Protein average weight
Not Available
Sequences
>DB00018 sequence (alpha-2A)
CDLPQTHSLGSRRTLMLLAQMRKISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMI
QQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVR
KYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE
>DB00018 sequence (alpha-2B)
CDLPQTHSLGSRRTLMLLAQMRRISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMI
QQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMNEDSILAVR
KYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE
>DB00018 sequence (alpha-2C)
CDLPQTHSLGSRRTLMLLAQMRRISLFSCLKDRRDFGFPQEEFGNQFQKAETIPVLHEMI
QQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMNEDSILAVR
KYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE
Download FASTA Format
Synonyms
Not Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AlferonInjection5000000 [arb'U]/mLSubcutaneousHemispherx Biopharma1989-10-10Not applicableUs
International/Other Brands
Alferon (Interferon Sciences Inc.) / Alferon LDO / Alferon N Injection
Categories
UNII
47BPR3V3MP
CAS number
Not Available

Pharmacology

Indication

For the intralesional treatment of refractory or recurring external condylomata acuminata.

Structured Indications
Pharmacodynamics

Interferon alfa-n3 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), beta-2 microglobulin, neopterin 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.

TargetActionsOrganism
AInterferon alpha/beta receptor 1
agonist
Human
AInterferon alpha/beta receptor 2
agonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
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 alfa-n3 is combined with Aldesleukin.Approved
Ambroxol acefyllinateThe metabolism of Ambroxol acefyllinate can be decreased when combined with Interferon alfa-n3.Experimental
AminophyllineThe metabolism of Aminophylline can be decreased when combined with Interferon alfa-n3.Approved
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Interferon alfa-n3.Investigational
ClozapineThe risk or severity of adverse effects can be increased when Interferon alfa-n3 is combined with Clozapine.Approved
DyphyllineThe metabolism of Dyphylline can be decreased when combined with Interferon alfa-n3.Approved
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Interferon alfa-n3.Withdrawn
MethadoneThe serum concentration of Methadone can be increased when it is combined with Interferon alfa-n3.Approved
RibavirinThe risk or severity of adverse effects can be increased when Interferon alfa-n3 is combined with Ribavirin.Approved
TheophyllineThe metabolism of Theophylline can be decreased when combined with Interferon alfa-n3.Approved
ZidovudineThe risk or severity of adverse effects can be increased when Interferon alfa-n3 is combined with Zidovudine.Approved
Food Interactions
Not Available

References

General References
  1. Sturgill MG, Rashidbaigi A, Liao MJ, Zhao XX, Hua J, Trout R, Knill JR, Grasing KW: Extravascular administration of interferon alfa-N3 increases serum exposure and 2-5(A) synthetase activity. J Clin Pharmacol. 2000 Jun;40(6):606-15. [PubMed:10868311]
External Links
ChEMBL
CHEMBL2109047
Therapeutic Targets Database
DAP001281
PharmGKB
PA164746228
Drugs.com
Drugs.com Drug Page

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentSevere Acute Respiratory Syndrome1
2TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections3

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Dosage forms
FormRouteStrength
InjectionSubcutaneous5000000 [arb'U]/mL
Prices
Unit descriptionCostUnit
Alferon n 5 million unit vial412.87USD ml
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)
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
Agonist
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. Dhalluin C, Ross A, Huber W, Gerber P, Brugger D, Gsell B, Senn H: Structural, kinetic, and thermodynamic analysis of the binding of the 40 kDa PEG-interferon-alpha2a and its individual positional isomers to the extracellular domain of the receptor IFNAR2. Bioconjug Chem. 2005 May-Jun;16(3):518-27. [PubMed:15898717]
  4. Ishii K, Shinohara M, Sawa M, Kogame M, Higami K, Sano M, Morita T, Sumino Y: Interferon alpha receptor 2 expression by peripheral blood monocytes in patients with a high viral load of hepatitis C virus genotype 1 showing substitution of amino Acid 70 in the core region. Intervirology. 2010;53(2):105-10. doi: 10.1159/000264200. Epub 2009 Dec 3. [PubMed:19955815]
  5. 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
Agonist
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. 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. Dhalluin C, Ross A, Huber W, Gerber P, Brugger D, Gsell B, Senn H: Structural, kinetic, and thermodynamic analysis of the binding of the 40 kDa PEG-interferon-alpha2a and its individual positional isomers to the extracellular domain of the receptor IFNAR2. Bioconjug Chem. 2005 May-Jun;16(3):518-27. [PubMed:15898717]
  4. Ishii K, Shinohara M, Sawa M, Kogame M, Higami K, Sano M, Morita T, Sumino Y: Interferon alpha receptor 2 expression by peripheral blood monocytes in patients with a high viral load of hepatitis C virus genotype 1 showing substitution of amino Acid 70 in the core region. Intervirology. 2010;53(2):105-10. doi: 10.1159/000264200. Epub 2009 Dec 3. [PubMed:19955815]
  5. Yano H, Ogasawara S, Momosaki S, Akiba J, Kojiro S, Fukahori S, Ishizaki H, Kuratomi K, Basaki Y, Oie S, Kuwano M, Kojiro M: Growth inhibitory effects of pegylated IFN alpha-2b on human liver cancer cells in vitro and in vivo. Liver Int. 2006 Oct;26(8):964-75. [PubMed:16953837]
  6. 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