Interferon Alfa-2b, Recombinant

ID Pharmacology Interactions References Trials Economics Properties Taxonomy

Targets (2)Enzymes (1)

Targets (2)Enzymes (1)Biointeractions (3)

Identification

Name

Interferon Alfa-2b, Recombinant

Accession Number

DB00105 (BTD00066, BIOD00066, DB05600)

Type

Biotech

Groups

Approved

Description

Interferon alpha 2b (human leukocyte clone hif-sn 206 protein moiety reduced). A type I interferon consisting of 165 amino acid residues with arginine in position 23. This protein is produced by recombinant DNA technology and resembles interferon secreted by leukocytes. It is used extensively as an antiviral or antineoplastic agent.

Protein structure

Protein chemical formula

C₈₆₀H₁₃₅₃N₂₂₉O₂₅₅S₉

Protein average weight

19271.0 Da

Sequences

>DB00105 sequence
CDLPQTHSLGSRRTLMLLAQMRRISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMI
QQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMNEDSILAVR
KYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE

Download FASTA Format

Synonyms

Interferon alfa-2b

Interferon α-2b

Intron (Interferon α2b)

Intron A

Intron A (Interferon α2b)

rIFN-alpha-2b

External IDs

99210-65-8 / Sch 30500 / YM 14090

Product Ingredients

Not Available

Approved Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Intron A	Kit			Merck Sharp & Dohme Limited	1986-06-04	Not applicable	US
Intron A	Injection, solution	19.2 ug/.5mL	Intralesional; Intramuscular; Subcutaneous	Merck Sharp & Dohme Limited	1986-06-04	Not applicable	US
Intron A	Kit			Merck Sharp & Dohme Limited	2014-08-11	Not applicable	US
Intron A	Solution	6000000 unit	Intramuscular; Intravenous; Subcutaneous	Merck Ltd.	1998-12-10	Not applicable	Canada
Intron A	Liquid	25000000 unit	Subcutaneous	Merck Ltd.	1999-09-23	Not applicable	Canada
Intron A	Kit			Merck Sharp & Dohme Limited	1986-06-04	Not applicable	US
Intron A	Injection, solution	11.6 ug/.5mL	Intramuscular; Subcutaneous	Merck Sharp & Dohme Limited	1986-06-04	Not applicable	US
Intron A	Kit			Merck Sharp & Dohme Limited	2014-08-11	Not applicable	US
Intron A	Solution	10000000 unit	Intramuscular; Intravenous; Subcutaneous	Merck Ltd.	1998-12-10	Not applicable	Canada
Intron A	Liquid	50000000 unit	Subcutaneous	Merck Ltd.	1999-09-23	Not applicable	Canada
Intron A	Kit			Merck Sharp & Dohme Limited	1986-06-04	Not applicable	US
Intron A	Kit			Merck Sharp & Dohme Limited	2014-08-11	Not applicable	US
Intron A	Liquid	15000000 unit	Subcutaneous	Merck Ltd.	1999-09-23	Not applicable	Canada
Intron A - Liq 5000000iu/ml	Liquid	5000000 unit	Intralesional; Intramuscular; Subcutaneous	Schering Plough (Brinny) Co.	1997-09-25	2001-07-18	Canada
Intron A Inj 10000000unit/vial	Liquid	10000000 unit	Subcutaneous	Avondale (Brinny) Chemical Company	1986-12-31	1999-07-22	Canada
Intron A Inj 3000000unit/vial	Liquid	3000000 unit	Subcutaneous	Avondale (Brinny) Chemical Company	1986-12-31	1999-07-22	Canada
Intron A Inj 5000000unit/vial	Liquid	5000000 unit	Subcutaneous	Avondale (Brinny) Chemical Company	1986-12-31	1999-07-22	Canada

Approved Generic Prescription Products

Not Available

Approved Over the Counter Products

Not Available

Unapproved/Other Products

Not Available

International Brands

Name	Company
Locteron	Not Available

Brand mixtures

Name	Labeller	Ingredients
Intron A	Merck Ltd.	Interferon Alfa-2b, Recombinant Water
Intron A - Kit (pws+diluent) 3000000iu/vial	Schering Plough (Brinny) Co.	Interferon Alfa-2b, Recombinant Water
Intron A - Kit (pws+diluent) 5000000iu/vial	Schering Plough (Brinny) Co.	Interferon Alfa-2b, Recombinant Water
Rebetron Ready To Use Solution (albumin(human)free) (6000000 Iu/ml and 200mg Capsules)	Schering Plough	Interferon Alfa-2b, Recombinant Ribavirin
Rebetron Solution (albumin (human) Free) (18 Miu Multi-dose Pen / 200mg Capsules)	Schering Plough	Interferon Alfa-2b, Recombinant Ribavirin

Categories

UNII

43K1W2T1M6

CAS number

98530-12-2

Pharmacology

Indication

For the treatment of hairy cell leukemia, malignant melanoma, and AIDS-related Kaposi's sarcoma.

Structured Indications

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

Absorption

Absorption is high (greater than 80%) when administered intramuscularly or subcutaneously.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Not Available

Route of elimination

Not Available

Half life

The elimination half-life following both intramuscular and subcutaneous injections was approximately 2 to 3 hours. The elimination half-life was approximately 2 hours following intravenous injection.

Clearance

Not Available

Toxicity

There is limited experience with overdosage. Postmarketing surveillance includes reports of patients receiving a single dose as great as 10 times the recommended dose. In general, the primary effects of an overdose are consistent with the effects seen with therapeutic doses of interferon alfa-2b. Hepatic enzyme abnormalities, renal failure, hemorrhage, and myocardial infarction have been reported with single administration overdoses and/or with longer durations of treatment than prescribed. Toxic effects after ingestion of interferon alfa-2b are not expected because interferons are poorly absorbed orally.

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 Alfa-2b, Recombinant is combined with Aldesleukin.	Approved
Ambroxol acefyllinate	The metabolism of Ambroxol acefyllinate can be decreased when combined with Interferon Alfa-2b, Recombinant.	Experimental
Aminophylline	The metabolism of Aminophylline can be decreased when combined with Interferon Alfa-2b, Recombinant.	Approved
Dyphylline	The metabolism of Dyphylline can be decreased when combined with Interferon Alfa-2b, Recombinant.	Approved
Methadone	The serum concentration of Methadone can be increased when it is combined with Interferon Alfa-2b, Recombinant.	Approved
Ribavirin	The risk or severity of adverse effects can be increased when Interferon Alfa-2b, Recombinant is combined with Ribavirin.	Approved
Telbivudine	The risk or severity of adverse effects can be increased when Interferon Alfa-2b, Recombinant is combined with Telbivudine.	Approved, Investigational
Theophylline	The metabolism of Theophylline can be decreased when combined with Interferon Alfa-2b, Recombinant.	Approved
Tizanidine	The serum concentration of Tizanidine can be increased when it is combined with Interferon Alfa-2b, Recombinant.	Approved
Zidovudine	The risk or severity of adverse effects can be increased when Interferon Alfa-2b, Recombinant is combined with Zidovudine.	Approved

Food Interactions

Avoid alcohol.

References

Synthesis Reference

Not Available

General References

Radhakrishnan R, Walter LJ, Hruza A, Reichert P, Trotta PP, Nagabhushan TL, Walter MR: Zinc mediated dimer of human interferon-alpha 2b revealed by X-ray crystallography. Structure. 1996 Dec 15;4(12):1453-63. [PubMed:8994971 ]

External Links

Resource	Link
UniProt	P01563
PharmGKB	PA164783990
Drug Product Database	1751
RxList	http://www.rxlist.com/cgi/generic/introna.htm

ATC Codes

L03AB05 — Interferon alfa-2b

AHFS Codes

08:18.20

PDB Entries

1RH2

FDA label

Download (3.52 MB)

MSDS

Not Available

Clinical Trials

Phase	Status	Purpose	Conditions	Count
1	Active Not Recruiting	Treatment	Melanoma	2
1	Completed	Not Available	Chronic Hepatitis C Infection	1
1	Completed	Treatment	Adult Solid Neoplasm	1
1	Completed	Treatment	Bladder Cancers / Urethral Cancer	1
1	Completed	Treatment	Cancer, Advanced / Tumors, Solid	1
1	Completed	Treatment	Chronic Hepatitis C Infection / Human Immunodeficiency Virus (HIV) Infections	1
1	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections / Kaposi s Sarcoma (KS)	1
1	Completed	Treatment	Melanoma	2
1	Completed	Treatment	Recurrent Melanoma / Recurrent Renal Cell Cancer / Stage III Melanoma / Stage IV Melanoma / Stage IV Renal Cell Cancer	1
1	Recruiting	Treatment	Solid Cancers	1
1, 2	Active Not Recruiting	Treatment	Melanoma	1
1, 2	Completed	Treatment	Chronic Hepatitis C Virus Infection / Genotype 1 / Relapses / Treatment-Experienced Patients	1
1, 2	Completed	Treatment	Melanoma	1
1, 2	Completed	Treatment	Recurrent Ovarian Cancer	1
1, 2	Recruiting	Treatment	Breastcancer / Neoplasms, Breast	1
1, 2	Recruiting	Treatment	Carcinoma, Colorectal / Colorectal Cancers / Colorectal Tumors / Neoplasms, Colorectal	1
1, 2	Recruiting	Treatment	Malignant Neoplasm of Pancreas Metastatic to Peritoneal Surface / Malignant Peritoneal Mesothelioma / Peritoneal Carcinomatosis	1
1, 2	Terminated	Treatment	Malignant Lymphomas / Precancerous/Nonmalignant Condition	1
1, 2	Terminated	Treatment	Renal Cell Adenocarcinoma	1
1, 2	Withdrawn	Treatment	Melanoma	1
2	Active Not Recruiting	Treatment	Ciliary Body and Choroid Melanoma, Medium/Large Size / Ciliary Body and Choroid Melanoma, Small Size / Iris Melanoma / Recurrent Intraocular Melanoma	1
2	Active Not Recruiting	Treatment	Cutaneous Melanoma / Metastatic Melanoma	1
2	Active Not Recruiting	Treatment	Recurrent Melanoma / Stage IIIA Skin Melanoma / Stage IIIB Skin Melanoma / Stage IIIC Skin Melanoma / Stage IV Skin Melanoma	1
2	Completed	Treatment	Chronic Hepatitis C Infection	1
2	Completed	Treatment	Clear Cell Renal Cell Carcinoma / Recurrent Renal Cell Cancer / Stage III Renal Cell Cancer / Stage IV Renal Cell Cancer	1
2	Completed	Treatment	Clear Cell Renal Cell Carcinoma / Renal Cell Carcinoma Recurrent / Stage IV Renal Cell Cancer	1
2	Completed	Treatment	Hepatitis C, Chronic	1
2	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections / Kaposi s Sarcoma (KS)	1
2	Completed	Treatment	Leukemias	1
2	Completed	Treatment	Leukemias / Malignant Lymphomas / Unspecified Childhood Solid Tumor, Protocol Specific	1
2	Completed	Treatment	Malignant Neoplasm of Pancreas	1
2	Completed	Treatment	Recurrent Melanoma / Stage IV Melanoma	1
2	Completed	Treatment	Recurrent Renal Cell Cancer / Stage IV Renal Cell Cancer	1
2	Completed	Treatment	Refractory Multiple Myeloma / Stage I Multiple Myeloma / Stage II Multiple Myeloma / Stage III Multiple Myeloma	1
2	Completed	Treatment	Renal Cell Adenocarcinoma / Stage IV Renal Cell Cancer	1
2	Recruiting	Treatment	Mucosal Melanoma	1
2	Terminated	Treatment	Clear Cell Renal Cell Carcinoma / Papillary Renal Cell Carcinoma / Recurrent Renal Cell Cancer / Stage III Renal Cell Cancer / Stage IV Renal Cell Cancer	1
2	Terminated	Treatment	Leukemias	1
2	Terminated	Treatment	Mycosis Fungoides (MF) / Neoplasms, Hematologic / T-Cell Lymphomas	1
2	Terminated	Treatment	Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma	1
2	Terminated	Treatment	Renal Cell Adenocarcinoma	1
2	Unknown Status	Treatment	Metastatic Renal Cell Carcinoma	1
2	Withdrawn	Treatment	Cancer, Advanced / Tumors, Solid	1
2	Withdrawn	Treatment	Malignant Melanoma / Melanoma	1
2, 3	Completed	Treatment	Chronic Hepatitis C Virus (HCV) Infection	1
3	Active Not Recruiting	Treatment	Neuroendocrine Carcinomas	1
3	Active Not Recruiting	Treatment	Recurrent Melanoma / Stage IIIB Skin Melanoma / Stage IIIC Skin Melanoma / Stage IV Skin Melanoma	1
3	Completed	Treatment	Leukemia,Myeloid, Chronic	1
3	Completed	Treatment	Malignant Melanoma / Recurrent Melanoma	1
3	Completed	Treatment	Melanoma / Neoplasms Metastasis	1
3	Completed	Treatment	Melanoma / Skin Cancers	1
3	Completed	Treatment	Stage I Multiple Myeloma / Stage II Multiple Myeloma / Stage III Multiple Myeloma	1
3	Recruiting	Treatment	Anaplastic Astrocytoma (AA) / Anaplastic Oligoastrocytoma / Glioblastomas	1
3	Recruiting	Treatment	Metastatic Non-Cutaneous Melanoma / Non-Cutaneous Melanoma / Recurrent Melanoma of the Skin / Recurrent Non-Cutaneous Melanoma / Stage III Mucosal Melanoma of the Head and Neck / Stage III Mucosal Melanoma of the Head and Neck AJCC v7 / Stage IIIA Skin Melanoma / Stage IIIB Skin Melanoma / Stage IIIC Skin Melanoma / Stage IV Skin Melanoma / Stage IVA Mucosal Melanoma of the Head and Neck / Stage IVA Mucosal Melanoma of the Head and Neck AJCC v7 / Stage IVB Mucosal Melanoma of the Head and Neck / Stage IVB Mucosal Melanoma of the Head and Neck AJCC v7 / Stage IVC Mucosal Melanoma of the Head and Neck / Stage IVC Mucosal Melanoma of the Head and Neck AJCC v7 / Stages III Skin Melanoma	1
3	Terminated	Treatment	Human Immunodeficiency Virus (HIV) Infections	1
3	Terminated	Treatment	Melanoma (Skin)	1
3	Withdrawn	Treatment	Gastro-intestinal Neuroendocrine Tumors	1
3	Withdrawn	Treatment	Hypertrophic Scars / Minor burns	1
4	Active Not Recruiting	Treatment	Conjunctival Intraepithelial Neoplasia / Corneal Intraepithelial Neoplasia	1
4	Active Not Recruiting	Treatment	Hepatitis B,Chronic	1
4	Recruiting	Treatment	Lymphoma, T-Cell, Cutaneous / Mycosis Fungoides (MF)	1
Not Available	Active Not Recruiting	Treatment	Stage IA Skin Melanoma / Stage IB Skin Melanoma / Stage IIA Skin Melanoma / Stage IIB Skin Melanoma / Stage IIC Skin Melanoma / Stage IIIA Skin Melanoma / Stage IIIB Skin Melanoma / Stage IIIC Skin Melanoma / Stage IV Skin Melanoma	1
Not Available	Completed	Not Available	Melanoma	2
Not Available	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections / Progressive Multifocal Leukoencephalopathy	1
Not Available	Recruiting	Treatment	Leukemias	1
Not Available	Terminated	Not Available	Chronic Hepatitis C Infection / Hepatitis C, Chronic	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Dosage forms

Form	Route	Strength
Injection, solution	Intralesional; Intramuscular; Subcutaneous	19.2 ug/.5mL
Injection, solution	Intramuscular; Subcutaneous	11.6 ug/.5mL
Kit
Kit; liquid; powder, for solution	Intralesional; Intramuscular; Intravenous; Subcutaneous
Liquid	Subcutaneous	15000000 unit
Liquid	Subcutaneous	25000000 unit
Liquid	Subcutaneous	50000000 unit
Liquid; powder, for solution	Intralesional; Intramuscular; Intravenous; Subcutaneous
Solution	Intramuscular; Intravenous; Subcutaneous	10000000 unit
Solution	Intramuscular; Intravenous; Subcutaneous	6000000 unit
Liquid; powder, for solution	Intralesional; Intramuscular; Subcutaneous
Liquid	Intralesional; Intramuscular; Subcutaneous	5000000 unit
Liquid	Subcutaneous	10000000 unit
Liquid	Subcutaneous	3000000 unit
Liquid	Subcutaneous	5000000 unit
Capsule; kit; liquid	Oral; Subcutaneous

Prices

Unit description	Cost	Unit
Intron-A 10000000 unit/0.2ml Kit (each Box Contains One 6 Dose 1.5ml Pen)	1110.84USD	box
Intron a 10 million unit pen	1068.12USD	pen
Intron-A 5000000 unit/0.2ml Kit Box	683.34USD	box
Intron a 5 million unit/ml pen	657.06USD	pen
Intron a 3 million unit/ml pen	394.21USD	pen

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
CA1341567	No	2008-02-19	2025-02-19	Canada
CA2201749	No	1999-06-15	2015-10-10	Canada

Properties

State

Liquid

Experimental Properties

Property	Value	Source
melting point (°C)	61 °C	Beldarrain, A. et al., Biochemistry 38:7865-7873 (1999)
hydrophobicity	-0.339	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 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
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 ]
Eid P, Tovey MG: Characterization of a domain of a human type I interferon receptor protein involved in ligand binding. J Interferon Cytokine Res. 1995 Mar;15(3):205-11. [PubMed:7584665 ]
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 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
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 ]
Khine AA, Lingwood CA: Functional significance of globotriaosyl ceramide in interferon-alpha(2)/type 1 interferon receptor-mediated antiviral activity. J Cell Physiol. 2000 Jan;182(1):97-108. [PubMed:10567921 ]
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

Enzymes

Details

1. Cytochrome P450 1A2

Kind: Protein
Organism: Human
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
Gene Name:: CYP1A2
Uniprot ID:: P05177
Uniprot Name:: Cytochrome P450 1A2
Molecular Weight:: 58293.76 Da

Drug created on June 13, 2005 07:24 / Updated on June 26, 2017 20:37

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Targets

References

References

Enzymes