DrugBank: Interferon beta-1a (DB00060)

targets (2)

Identification

Name

Interferon beta-1a

Accession Number

DB00060 (BIOD00093, BTD00093)

Type

biotech

Groups

approved

Description

Human interferon beta (166 residues), glycosylated, MW=22.5kD. It is produced by mammalian cells (Chinese Hamster Ovary cells) into which the human interferon beta gene has been introduced. The amino acid sequence of Avonex is identical to that of natural human interferon beta.

Protein structure

Display: 3D Structure

Protein chemical formula

C₉₀₈H₁₄₀₈N₂₄₆O₂₅₂S₇

Protein average weight

20027.0000

Sequences

>DB00060 sequence
MSYNLLGFLQRSSNFQCQKLLWQLNGRLEYCLKDRMNFDIPEEIKQLQQFQKEDAALTIY
EMLQNIFAIFRQDSSSTGWNETIVENLLANVYHQINHLKTVLEEKLEKEDFTRGKLMSSL
HLKRYYGRILHYLKAKEYSHCAWTIVRVEILRNFYFINRLTGYLRN

FASTA

Synonyms

Fibroblast interferon
IFN-beta
Interferon beta precursor

Brand names

Avonex
Avonex (Biogen Inc)
Belerofon

Brand name mixtures

Not Available

Categories

Immunomodulatory Agents
Antiviral Agents

CAS number

145258-61-3

Taxonomy

Kingdom

Not Available

Classes

Not Available

Substructures

Not Available

Pharmacology

Indication

For treatment of relapsing/remitting multiple sclerosis, also for condyloma acuminatum

Pharmacodynamics

Interferon beta 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. Type I interferons also induce the synthesis of several key antiviral mediators including 2'-5' oligoadenylate synthetase (2'-5' A synthetase), beta-2 microglobulin and neopterin.

Mechanism of action

Interferon beta 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 beta binds more stably to type I interferon receptors than interferon alpha.

Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Route of elimination

Not Available

Half life

10 hrs

Clearance

33-55 L/hour [Healthy SC injection of 60 mcg]

Toxicity

Not Available

Affected organisms

Not Available

Pathways

Not Available

Pharmacoeconomics

Manufacturers

Biogen Idec

Packagers

Dosage forms

Form	Route	Strength
Liquid	Subcutaneous
Solution	Intramuscular

Prices

Unit description	Cost	Unit
Avonex 4 30 mcg/vial Kit 1 Box = 4 Vials ( 0.5ml Per Vial)	3252.29 USD	box
Avonex Prefilled (1 Box = 1 Kit = Four 30 mcg/0.5ml Syringes) Box	3252.29 USD	box
Avonex admin pack 30 mcg vial	781.8 USD	vial
Rebif 22 mcg/0.5 ml syringe	247.79 USD	syringe
Rebif 44 mcg/0.5 ml syringe	247.79 USD	syringe

Patents

Country	Patent Number	Approved	Expires
Canada	1341604	2010-05-04	2027-05-04

Properties

State

liquid

Melting point

Not Available

Experimental Properties

Property	Value	Source
hydrophobicity	-0.427	PhysProp
isoelectric point	8.93	Various sources

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
UniProt	P01574
Genbank	V00534
PharmGKB	PA10351
Drug Product Database	2237319
RxList	http://www.rxlist.com/cgi/generic3/rebif.htm
Drugs.com	http://www.drugs.com/cdi/interferon-beta-1a.html
Wikipedia	http://en.wikipedia.org/wiki/Interferon_beta-1a

ATC Codes

L04AA23
L03AB07

AHFS Codes

92:00.00

PDB Entries

1AU1

FDA label

show (63 KB)

MSDS

Not Available

Interactions

Drug Interactions

Drug	Interaction

Food Interactions

Not Available

Targets
1. Interferon-alpha/beta receptor alpha chain Pharmacological action: yes Actions: agonist 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 Organism class: human UniProt ID: P17181 Gene: IFNAR1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Russell-Harde D, Wagner TC, Perez HD, Croze E: Formation of a uniquely stable type I interferon receptor complex by interferon beta is dependent upon particular interactions between interferon beta and its receptor and independent of tyrosine phosphorylation. Biochem Biophys Res Commun. 1999 Feb 16;255(2):539-44. Pubmed van Koetsveld PM, Vitale G, de Herder WW, Feelders RA, van der Wansem K, Waaijers M, van Eijck CH, Speel EJ, Croze E, van der Lely AJ, Lamberts SW, Hofland LJ: Potent inhibitory effects of type I interferons on human adrenocortical carcinoma cell growth. J Clin Endocrinol Metab. 2006 Nov;91(11):4537-43. Epub 2006 Aug 15. Pubmed Dupont SA, Goelz S, Goyal J, Green M: Mechanisms for regulation of cellular responsiveness to human IFN-beta1a. J Interferon Cytokine Res. 2002 Apr;22(4):491-501. Pubmed Runkel L, De Dios C, Karpusas M, Baker D, Li Z, Zafari M, Betzenhauser M, Muldowney C, Miller S, Redlich PN, Grossberg SE, Whitty A, Hochman PS: Mapping of IFN-beta epitopes important for receptor binding and biologic activation: comparison of results achieved using antibody-based methods and alanine substitution mutagenesis. J Interferon Cytokine Res. 2001 Nov;21(11):931-41. Pubmed 2. Interferon-alpha/beta receptor beta chain Pharmacological action: yes Receptor for interferons alpha and beta. Isoform 1 and isoform 3 are directly involved in signal transduction due to their interaction with the TYR kinase, JAK1. Isoform 1 also interacts with the transcriptional factors, STAT1 and STAT2. Both forms are potent inhibitors of type I IFN activity Organism class: human UniProt ID: P48551 Gene: IFNAR2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: van Koetsveld PM, Vitale G, de Herder WW, Feelders RA, van der Wansem K, Waaijers M, van Eijck CH, Speel EJ, Croze E, van der Lely AJ, Lamberts SW, Hofland LJ: Potent inhibitory effects of type I interferons on human adrenocortical carcinoma cell growth. J Clin Endocrinol Metab. 2006 Nov;91(11):4537-43. Epub 2006 Aug 15. Pubmed Runkel L, De Dios C, Karpusas M, Baker D, Li Z, Zafari M, Betzenhauser M, Muldowney C, Miller S, Redlich PN, Grossberg SE, Whitty A, Hochman PS: Mapping of IFN-beta epitopes important for receptor binding and biologic activation: comparison of results achieved using antibody-based methods and alanine substitution mutagenesis. J Interferon Cytokine Res. 2001 Nov;21(11):931-41. Pubmed

Targets

1. Interferon-alpha/beta receptor alpha chain

Pharmacological action: yes
Actions: agonist

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

Organism class: human
UniProt ID: P17181 Link_out

Gene: IFNAR1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Russell-Harde D, Wagner TC, Perez HD, Croze E: Formation of a uniquely stable type I interferon receptor complex by interferon beta is dependent upon particular interactions between interferon beta and its receptor and independent of tyrosine phosphorylation. Biochem Biophys Res Commun. 1999 Feb 16;255(2):539-44. Pubmed
van Koetsveld PM, Vitale G, de Herder WW, Feelders RA, van der Wansem K, Waaijers M, van Eijck CH, Speel EJ, Croze E, van der Lely AJ, Lamberts SW, Hofland LJ: Potent inhibitory effects of type I interferons on human adrenocortical carcinoma cell growth. J Clin Endocrinol Metab. 2006 Nov;91(11):4537-43. Epub 2006 Aug 15. Pubmed
Dupont SA, Goelz S, Goyal J, Green M: Mechanisms for regulation of cellular responsiveness to human IFN-beta1a. J Interferon Cytokine Res. 2002 Apr;22(4):491-501. Pubmed
Runkel L, De Dios C, Karpusas M, Baker D, Li Z, Zafari M, Betzenhauser M, Muldowney C, Miller S, Redlich PN, Grossberg SE, Whitty A, Hochman PS: Mapping of IFN-beta epitopes important for receptor binding and biologic activation: comparison of results achieved using antibody-based methods and alanine substitution mutagenesis. J Interferon Cytokine Res. 2001 Nov;21(11):931-41. Pubmed

2. Interferon-alpha/beta receptor beta chain

Pharmacological action: yes

Receptor for interferons alpha and beta. Isoform 1 and isoform 3 are directly involved in signal transduction due to their interaction with the TYR kinase, JAK1. Isoform 1 also interacts with the transcriptional factors, STAT1 and STAT2. Both forms are potent inhibitors of type I IFN activity

Organism class: human
UniProt ID: P48551 Link_out

Gene: IFNAR2 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

van Koetsveld PM, Vitale G, de Herder WW, Feelders RA, van der Wansem K, Waaijers M, van Eijck CH, Speel EJ, Croze E, van der Lely AJ, Lamberts SW, Hofland LJ: Potent inhibitory effects of type I interferons on human adrenocortical carcinoma cell growth. J Clin Endocrinol Metab. 2006 Nov;91(11):4537-43. Epub 2006 Aug 15. Pubmed
Runkel L, De Dios C, Karpusas M, Baker D, Li Z, Zafari M, Betzenhauser M, Muldowney C, Miller S, Redlich PN, Grossberg SE, Whitty A, Hochman PS: Mapping of IFN-beta epitopes important for receptor binding and biologic activation: comparison of results achieved using antibody-based methods and alanine substitution mutagenesis. J Interferon Cytokine Res. 2001 Nov;21(11):931-41. Pubmed

Comments

Drug created on June 13, 2005 07:24 / Updated on December 22, 2010 08:48

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.