Identification

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Name
Interferon alfa-n1
Accession Number
DB00011  (BTD00096, BIOD00096, DB00084)
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Interferons
Description

Purified, natural (n is for natural) glycosylated human interferon alpha proteins 166 residues

Protein structure
Db00011
Protein chemical formula
C860H1353N227O255S9
Protein average weight
19241.1 Da
Sequences
>DB00011 sequence
CDLPQTHSLGSRRTLMLLAQMRKISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMI
QQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVR
KYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE
Download FASTA Format
Synonyms
  • Interferon alpha-n1 (INS)
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Wellferon Inj 10 000 000unit/mlLiquidIntramuscular; SubcutaneousThe Wellcome Foundation Ltd.1992-12-312000-08-01Canada
Wellferon Inj 3000000unit/mlLiquidIntramuscular; SubcutaneousThe Wellcome Foundation Ltd.1992-12-312000-08-01Canada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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International/Other Brands
Wellferon (GlaxoSmithKline)
Categories
UNII
41697D4Z5C
CAS number
74899-72-2

Pharmacology

Indication

For treatment of venereal or genital warts caused by the Human Papiloma Virus

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.

TargetActionsOrganism
AInterferon alpha/beta receptor 2
agonist
Humans
AInterferon alpha/beta receptor 1
agonist
Humans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

1.2 hours (mammalian reticulocytes, in vitro); >20 hours (yeast, in vivo); >10 hours (Escherichia coli, in vivo).

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Interferon alfa-n1.
(S)-WarfarinThe risk or severity of bleeding can be increased when (S)-Warfarin is combined with Interferon alfa-n1.
2-MethoxyethanolThe risk or severity of adverse effects can be increased when Interferon alfa-n1 is combined with 2-Methoxyethanol.
3-isobutyl-1-methyl-7H-xanthineThe metabolism of 3-isobutyl-1-methyl-7H-xanthine can be decreased when combined with Interferon alfa-n1.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when 4-hydroxycoumarin is combined with Interferon alfa-n1.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Interferon alfa-n1.
7-DeazaguanineThe metabolism of 7-Deazaguanine can be decreased when combined with Interferon alfa-n1.
7,9-DimethylguanineThe metabolism of 7,9-Dimethylguanine can be decreased when combined with Interferon alfa-n1.
8-azaguanineThe metabolism of 8-azaguanine can be decreased when combined with Interferon alfa-n1.
8-chlorotheophyllineThe metabolism of 8-chlorotheophylline can be decreased when combined with Interferon alfa-n1.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Avoid alcohol.

References

Synthesis Reference

Vladimir G. Debabov, Jury D. Tsygankov, Andrei J. Chistoserdov, Evgeny D. Sverdlov, Lara S. Izotova, Sergei V. Kostrov, Viktor E. Sterkin, Vladimir P. Kuznetsov, Sergei V. Belyaev, Galina S. Monastyrskaya, Irina S. Salomatina, Grigory M. Dolganov, Sergei G. Arsenian, Sergei A. Tsarev, Jury I. Kozlov, Alexandr Y. Strongin, Vsevolod I. Ogarkov, Jury A. Ovchinnikov, "Method for producing human leukocyte interferon alpha-2." U.S. Patent US4680260, issued January, 1982.

US4680260
General References
Not Available
External Links
UniProt
P01563
Genbank
J00207
PubChem Substance
46506227
ChEMBL
CHEMBL2108509
Therapeutic Targets Database
DAP001280
PharmGKB
PA164746538
ATC Codes
L03AB06 — Interferon alfa-n1

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Kaposi s Sarcoma (KS)2
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
LiquidIntramuscular; Subcutaneous
Prices
Not Available
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
Humans
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. Krown SE: Interferon treatment of renal cell carcinoma. Current status and future prospects. Cancer. 1987 Feb 1;59(3 Suppl):647-51. [PubMed:10822464]
  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
Humans
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. Krown SE: Interferon treatment of renal cell carcinoma. Current status and future prospects. Cancer. 1987 Feb 1;59(3 Suppl):647-51. [PubMed:10822464]
  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]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Delaporte E, Renton KW: Cytochrome P4501A1 and cytochrome P4501A2 are downregulated at both transcriptional and post-transcriptional levels by conditions resulting in interferon-alpha/beta induction. Life Sci. 1997;60(10):787-96. doi: 10.1016/s0024-3205(97)00006-4. [PubMed:9064483]

Drug created on June 13, 2005 07:24 / Updated on December 02, 2019 05:14