Interferon alfa-n1

Identification

Name

Interferon alfa-n1

Accession Number

DB00011

Description

Interferon alfa-n1 consists of purified, natural (n is for natural) alpha interferon subtypes, at least two of which are glycosylated. This differs from recombinant alpha interferons, which are individual non-glycosylated proteins produced from individual alpha interferon genes.

Type

Biotech

Groups

Approved, Investigational

Biologic Classification

Protein Based Therapies
Interferons

Protein Structure

Protein Chemical Formula: C₈₆₀H₁₃₅₃N₂₂₇O₂₅₅S₉
Protein Average Weight: 19241.1 Da

Sequences

>DB00011 sequence
CDLPQTHSLGSRRTLMLLAQMRKISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMI
QQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVR
KYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE

Download FASTA Format

Synonyms

Interferon alfa-n1
Interferon alpha-n1 (INS)

Pharmacology

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Drug Discovery

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Indication

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

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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.

Target	Actions	Organism
AInterferon alpha/beta receptor 1	agonist	Humans
AInterferon alpha/beta receptor 2	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

Adverse Effects

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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.

Drug	Interaction
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Abatacept	The risk or severity of adverse effects can be increased when Interferon alfa-n1 is combined with Abatacept.
Abciximab	The risk or severity of bleeding can be increased when Abciximab is combined with Interferon alfa-n1.
Acenocoumarol	The metabolism of Acenocoumarol can be decreased when combined with Interferon alfa-n1.
Acetaminophen	The metabolism of Acetaminophen can be decreased when combined with Interferon alfa-n1.
Acetylsalicylic acid	The risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Interferon alfa-n1.
Acyclovir	The metabolism of Acyclovir can be decreased when combined with Interferon alfa-n1.
Adalimumab	The risk or severity of adverse effects can be increased when Interferon alfa-n1 is combined with Adalimumab.
Adenovirus type 7 vaccine live	The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Interferon alfa-n1.
Agomelatine	The metabolism of Agomelatine can be decreased when combined with Interferon alfa-n1.
Albendazole	The metabolism of Albendazole can be decreased when combined with Interferon alfa-n1.

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Food Interactions

Avoid alcohol.

Products

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International/Other Brands

Wellferon (GlaxoSmithKline)

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Wellferon Inj 10 000 000unit/ml	Liquid		Intramuscular; Subcutaneous	The Wellcome Foundation Ltd.	1992-12-31	2000-08-01
Wellferon Inj 3000000unit/ml	Liquid		Intramuscular; Subcutaneous	The Wellcome Foundation Ltd.	1992-12-31	2000-08-01

Chemical Identifiers

UNII: 41697D4Z5C
CAS number: 74899-72-2

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
RxNav: 202912
ChEMBL: CHEMBL2108509
Therapeutic Targets Database: DAP001280
PharmGKB: PA164746538

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
2	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections	1
1	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections / Kaposi’s sarcoma	2
Not Available	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections	2

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Liquid	Intramuscular; Subcutaneous
Solution	Subcutaneous

Prices

Not Available

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

Targets

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Details1. Interferon alpha/beta receptor 1

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

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]
Krown SE: Interferon treatment of renal cell carcinoma. Current status and future prospects. Cancer. 1987 Feb 1;59(3 Suppl):647-51. [PubMed:10822464]
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]
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Details2. Interferon alpha/beta receptor 2

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

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]
Krown SE: Interferon treatment of renal cell carcinoma. Current status and future prospects. Cancer. 1987 Feb 1;59(3 Suppl):647-51. [PubMed:10822464]
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]
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Enzymes

Details1. Cytochrome P450 1A2

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

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 13:24 / Updated on February 21, 2021 18:50

Interferon alfa-n1

Identification

Pharmacology

Interactions

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Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

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References

Enzymes

References