Identification

Name
Interferon gamma-1b
Accession Number
DB00033  (BTD00017, BIOD00017)
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Interferons
Description

Human Interferon gamma-1b (140 residues), produced from E. coli. Production of Actimmune is achieved by fermentation of a genetically engineered Escherichia coli bacterium containing the DNA which encodes for the human protein. Purification of the product is achieved by conventional column chromatography. The sequence displayed is a cDNA sequence which codes for human interferon gamma, as described by Gray et. al. and not specifically interferon gamma 1b.

Protein structure
Db00033
Protein chemical formula
C761H1206N214O225S6
Protein average weight
17145.6 Da
Sequences
>DB00033 sequence
CYCQDPYVKEAENLKKYFNAGHSDVADNGTLFLGILKNWKEESDRKIMQSQIVSFYFKLF
KNFKDDQSIQKSVETIKEDMNVKFFNSNKKKRDDFEKLTNYSVTDLNVQRKAIHELIQVM
AELSPAAKTGKRKRSQMLFRGRRASQ
Download FASTA Format
Synonyms
  • IFN-gamma-1b
  • Interferon gamma-1b, recombinant
  • Interferon gamma-2a
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ActimmuneInjection, solution100 ug/.5mLSubcutaneousHznp Usa, Inc.2013-12-01Not applicableUs
ActimmuneInjection, solution100 ug/.5mLSubcutaneousHorizon Pharma, Inc.2013-12-01Not applicableUs
International/Other Brands
Immukin
Categories
UNII
21K6M2I7AG
CAS number
98059-61-1

Pharmacology

Indication

Interferon gamma-1b is used for the treatment of Chronic granulomatous disease and Osteopetrosis.

Structured Indications
Pharmacodynamics

IFN gamma stimulates expression of the immunoglobulin heavy chain C gamma 3 and C gamma 2a germline transcripts in B cells. Many components of the antigen presentation pathways are also up-regulated by interferon gamma. It is also a potent activator of macrophages, it has antiproliferative effects on transformed cells and it can potentiate the antiviral and antitumor effects of type I interferons. Interferon gamma may also help the body regulate the activity of fibroblasts. By directly blocking the multiplication of fibroblasts and inhibiting the production and action of TGF-b, a potent scar-inducing molecule, Interferon gamma-1b may prevent excessive scarring.

Mechanism of action

Binds directly to the type II interferon gamma receptor IFNGR1, leading to a complex of IFNGR1 and IFNGR2. This activates JAK1 and JAK2 kinases which form a STAT1 docking site. This leads to STAT1 phosphorylation, nuclear translocation and initiation of gene transcription of multiple immune-related genes.

TargetActionsOrganism
AInterferon gamma receptor 1
binder
Human
AInterferon gamma receptor 2
binder
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
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
Ambroxol acefyllinateThe metabolism of Ambroxol acefyllinate can be decreased when combined with Interferon gamma-1b.Experimental, Investigational
AminophyllineThe metabolism of Aminophylline can be decreased when combined with Interferon gamma-1b.Approved
DyphyllineThe metabolism of Dyphylline can be decreased when combined with Interferon gamma-1b.Approved
TheophyllineThe metabolism of Theophylline can be decreased when combined with Interferon gamma-1b.Approved
TizanidineThe serum concentration of Tizanidine can be increased when it is combined with Interferon gamma-1b.Approved
ZidovudineThe risk or severity of adverse effects can be increased when Interferon gamma-1b is combined with Zidovudine.Approved
Food Interactions
Not Available

References

Synthesis Reference

Irwin A. Braude, "Production of human IFN-gamma (immune) interferon." U.S. Patent US4376821, issued December, 1975.

US4376821
General References
  1. Kantoch M, Dobrowolska H, Jarzabek Z, Jankowski M, Sadowski W, Janicki P: [Distribution and characteristics of Poliovirus strains circulating in Poland in 1968-1972. Genetic variation of strains isolated in various secretion periods and clones isolated from vaccines]. Med Dosw Mikrobiol. 1975;27(4):353-63. [PubMed:55526]
  2. Ormas P, Pompa G, Beretta C, Faustini R: [The effects of some polypeptides on the systemic blood pressure of sheep (author's transl)]. Folia Vet Lat. 1975 Jan-Mar;5(1):45-54. [PubMed:3458]
  3. Selitrennikoff CP, Sonneborn DR: Alkaline phosphatase of Blastocladiella emersonii: partial purification and characterization. J Bacteriol. 1977 Apr;130(1):249-56. [PubMed:15978]
  4. Gray PW, Goeddel DV: Structure of the human immune interferon gene. Nature. 1982 Aug 26;298(5877):859-63. [PubMed:6180322]
  5. Ealick SE, Cook WJ, Vijay-Kumar S, Carson M, Nagabhushan TL, Trotta PP, Bugg CE: Three-dimensional structure of recombinant human interferon-gamma. Science. 1991 May 3;252(5006):698-702. [PubMed:1902591]
  6. Ikeda H, Old LJ, Schreiber RD: The roles of IFN gamma in protection against tumor development and cancer immunoediting. Cytokine Growth Factor Rev. 2002 Apr;13(2):95-109. [PubMed:11900986]
  7. Chesler DA, Reiss CS: The role of IFN-gamma in immune responses to viral infections of the central nervous system. Cytokine Growth Factor Rev. 2002 Dec;13(6):441-54. [PubMed:12401479]
  8. Dessein A, Kouriba B, Eboumbou C, Dessein H, Argiro L, Marquet S, Elwali NE, Rodrigues V, Li Y, Doumbo O, Chevillard C: Interleukin-13 in the skin and interferon-gamma in the liver are key players in immune protection in human schistosomiasis. Immunol Rev. 2004 Oct;201:180-90. [PubMed:15361241]
  9. Joseph AM, Kumar M, Mitra D: Nef: "necessary and enforcing factor" in HIV infection. Curr HIV Res. 2005 Jan;3(1):87-94. [PubMed:15638726]
  10. Copeland KF: Modulation of HIV-1 transcription by cytokines and chemokines. Mini Rev Med Chem. 2005 Dec;5(12):1093-101. [PubMed:16375755]
  11. Schroder K, Hertzog PJ, Ravasi T, Hume DA: Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol. 2004 Feb;75(2):163-89. Epub 2003 Oct 2. [PubMed:14525967]
External Links
UniProt
P01579
Genbank
X13274
PubChem Substance
46507194
ChEMBL
CHEMBL1201564
Therapeutic Targets Database
DAP001286
PharmGKB
PA164746386
Drugs.com
Drugs.com Drug Page
Wikipedia
Interferon_gamma-1b
FDA label
Download (605 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0TerminatedBasic SciencePlaque Psoriasis1
1Active Not RecruitingTreatmentGlioblastoma or Gliosarcoma1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections2
1CompletedTreatmentRecurrent Ovarian Epithelial Cancer1
1RecruitingBasic ScienceChronic Granulomatous Disease (CGD)1
1Unknown StatusSupportive CareAdverse Effects in the Therapeutic Use of Interferon1
1, 2CompletedTreatmentAnterior Uveitis (AU) / Uveitis1
1, 2CompletedTreatmentCystic Fibrosis (CF)2
1, 2CompletedTreatmentMacular Diseases / Retinal Diseases1
1, 2RecruitingTreatmentBreast Cancer, Male / Cancer, Breast / Her2-Positive Breast Cancer / Malignant Neoplasm of Female Breast1
1, 2SuspendedTreatmentInherited Ophthalmic Diseases / Inherited Retinal Degeneration1
1, 2TerminatedTreatmentMucinous Adenocarcinoma of the Colon / Mucinous Adenocarcinoma of the Rectum / Recurrent Colon Cancer / Recurrent Rectal Cancer / Signet Ring Adenocarcinoma of the Colon / Signet Ring Adenocarcinoma of the Rectum / Stage IVA Colon Cancer / Stage IVA Rectal Cancer / Stage IVB Colon Cancer / Stage IVB Rectal Cancer1
1, 2TerminatedTreatmentNon-Hodgkin's Lymphoma (NHL)1
2CompletedTreatmentColorectal Cancers1
2CompletedTreatmentFibrosis, Liver / Liver Cirrhosis1
2CompletedTreatmentFriedreich's Ataxia1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Meningitis, Cryptococcal1
2RecruitingTreatmentAutosomal Dominant Osteopetrosis Type 21
2RecruitingTreatmentOsteopetrosis1
2RecruitingTreatmentRecurrent Mycosis Fungoides and Sezary Syndrome / Refractory Mycosis Fungoides / Stage IB Mycosis Fungoides and Sezary Syndrome / Stage II Mycosis Fungoides and Sezary Syndrome / Stage IIA Mycosis Fungoides and Sezary Syndrome / Stage IIB Mycosis Fungoides and Sezary Syndrome / Stage III Mycosis Fungoides and Sezary Syndrome / Stage IIIA Mycosis Fungoides and Sezary Syndrome / Stage IIIB Mycosis Fungoides and Sezary Syndrome / Stage IV Mycosis Fungoides and Sezary Syndrome / Stage IVA Mycosis Fungoides and Sezary Syndrome / Stage IVB Mycosis Fungoides and Sezary Syndrome1
2TerminatedTreatmentLung Infection1
2Unknown StatusTreatmentViral Hepatitis B1
2, 3CompletedTreatmentMalignant Lymphomas1
3CompletedTreatmentFriedreich's Ataxia3
3TerminatedDiagnosticOvarian Carcinoma / Primary Peritoneal Cancer1
3TerminatedTreatmentChronic Lung Diseases / Idiopathic Pulmonary Fibrosis (IPF) / Pulmonary Fibrosis2
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Dosage forms
FormRouteStrength
Injection, solutionSubcutaneous100 ug/.5mL
Prices
Unit descriptionCostUnit
Actimmune 2 million unit vial344.4USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6936695No2005-08-302022-08-30Us
US6936694No2005-08-302022-08-30Us

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)61 °CBeldarrain, A. et al., Biochemistry 38:7865-7873 (1999)
hydrophobicity-0.823Not Available
isoelectric point9.54Not 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
Binder
General Function
Interferon-gamma receptor activity
Specific Function
Receptor for interferon gamma. Two receptors bind one interferon gamma dimer.
Gene Name
IFNGR1
Uniprot ID
P15260
Uniprot Name
Interferon gamma receptor 1
Molecular Weight
54404.07 Da
References
  1. Matsuda A, Ebihara N, Kumagai N, Fukuda K, Ebe K, Hirano K, Sotozono C, Tei M, Hasegawa K, Shimizu M, Tamari M, Namba K, Ohno S, Mizuki N, Ikezawa Z, Shirakawa T, Hamuro J, Kinoshita S: Genetic polymorphisms in the promoter of the interferon gamma receptor 1 gene are associated with atopic cataracts. Invest Ophthalmol Vis Sci. 2007 Feb;48(2):583-9. [PubMed:17251453]
  2. Yao X, Chen ZQ, Gong JQ, Chen M, Li AS, Liu J: The interferon-gamma receptor gene polymorphisms (Val14Met and Gln64Arg) are not associated with systemic lupus erythematosus in Chinese patients. Arch Dermatol Res. 2007 Oct;299(8):367-71. Epub 2007 Jul 6. [PubMed:17618444]
  3. 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
Binder
General Function
Interferon-gamma receptor activity
Specific Function
Part of the receptor for interferon gamma. Required for signal transduction. This accessory factor is an integral part of the IFN-gamma signal transduction pathway and is likely to interact with GA...
Gene Name
IFNGR2
Uniprot ID
P38484
Uniprot Name
Interferon gamma receptor 2
Molecular Weight
37805.97 Da
References
  1. Park-Min KH, Serbina NV, Yang W, Ma X, Krystal G, Neel BG, Nutt SL, Hu X, Ivashkiv LB: FcgammaRIII-dependent inhibition of interferon-gamma responses mediates suppressive effects of intravenous immune globulin. Immunity. 2007 Jan;26(1):67-78. [PubMed:17239631]
  2. Yao X, Chen ZQ, Gong JQ, Chen M, Li AS, Liu J: The interferon-gamma receptor gene polymorphisms (Val14Met and Gln64Arg) are not associated with systemic lupus erythematosus in Chinese patients. Arch Dermatol Res. 2007 Oct;299(8):367-71. Epub 2007 Jul 6. [PubMed:17618444]
  3. 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
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 un...
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 November 06, 2017 06:43