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Identification
Name Infliximab
Accession Number DB00065 (BIOD00004, BTD00004)
Type biotech
Groups approved
Description

Tumor necrosis factor (TNF-alpha) binding antibody (chimeric IgG1). It is composed of human constant and murine variable regions. Infliximab is produced by a recombinant cell line cultured by continuous perfusion
Protein structure Db00065
Display: 3D Structure
Protein chemical formula C6428H9912N1694O1987S46
Protein average weight 144190.3000
Sequences
Synonyms
  • Ig gamma-1 chain C region
Brand names
  • Remicade
  • Remicade (Centocor Inc)
Brand name mixtures Not Available
Categories
  • Immunomodulatory Agents
  • Immunosuppressive Agents
CAS number 170277-31-3
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication To manage the signs and symptoms, as well as to induce and maintain clinical remission in adults with moderate to severe active Crohn's disease or ulcerative colitis. Also used to manage signs and symptoms of rheumatoid arthritis (in conjunction with methotrexate), ankylosing spondylitis, psoriatic arthritis, and juvenile arthritis.
Pharmacodynamics Infliximab is a chimeric human-murine anti-human tumor necrosis factor (TNF) monoclonal antibody. It binds to tumor necrosis factor alpha (TNFa) and inhibits binding of TNFa with its receptors. This reduces production of pro-inflammatory cytokines such as interleukins (IL) 1 and 6. This also limits leukocyte migration and expression of adhesion molecules by endothelial cells and leukocytes. Infliximab also limits the activation of neutrophil and eosinophil functional activity, reduces production of tissue degrading enzymes produced by synoviocytes and/or chondrocytes. Infliximab decreases synovitis and joint erosions in collagen-induced arthritis and allows eroded joints to heal.
Mechanism of action Infliximab neutralizes the biological activity of TNFa by binding with high affinity to the soluble and transmembrane forms of TNFa and inhibits binding of TNFa with its receptors. Infliximab does not neutralize TNFb (lymphotoxin a), a related cytokine that utilizes the same receptors as TNFa. Neutralization of the biological activity of TNFa leads to an overall reduction in inflammation.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism

Most likely removed by opsonization via the reticuloendothelial system when bound to T lymphocytes, or by human antimurine antibody production
Route of elimination Not Available
Half life 9.5 days
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • J&J and Mitsubisi Tanabe
Packagers
Dosage forms
Form Route Strength
Powder, for solution Intravenous
Prices
Unit description Cost Unit
Remicade 100 mg Solution Vial 821.02 USD vial
Remicade 100 mg vial 789.44 USD vial
Patents
Country Patent Number Approved Expires
Canada 2106299 2001-02-06 2012-03-18
Properties
State liquid
Melting point 61 oC (FAB fragment), 71 oC (whole mAb) - Vermeer, A.W.P. & Norde, W., Biophys. J. 78:394-404 (2000).
Experimental Properties
Property Value Source
hydrophobicity -0.441 PhysProp
isoelectric point 8.25 Various sources
References
Synthesis Reference Not Available
General Reference
  1. Knight DM, Trinh H, Le J, Siegel S, Shealy D, McDonough M, Scallon B, Moore MA, Vilcek J, Daddona P, et al.: Construction and initial characterization of a mouse-human chimeric anti-TNF antibody. Mol Immunol. 1993 Nov;30(16):1443-53. Pubmed
  2. Dubinsky MC, Fleshner PP: Treatment of Crohn’s Disease of Inflammatory, Stenotic, and Fistulizing Phenotypes. Curr Treat Options Gastroenterol. 2003 Jun;6(3):183-200. Pubmed
  3. Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogezand RA, Podolsky DK, Sands BE, Braakman T, DeWoody KL, Schaible TF, van Deventer SJ: Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med. 1999 May 6;340(18):1398-405. Pubmed
  4. Sands BE, Anderson FH, Bernstein CN, Chey WY, Feagan BG, Fedorak RN, Kamm MA, Korzenik JR, Lashner BA, Onken JE, Rachmilewitz D, Rutgeerts P, Wild G, Wolf DC, Marsters PA, Travers SB, Blank MA, van Deventer SJ: Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med. 2004 Feb 26;350(9):876-85. Pubmed
  5. Hanauer SB: Crohn’s disease: step up or top down therapy. Best Pract Res Clin Gastroenterol. 2003 Feb;17(1):131-7. Pubmed
External Links
Resource Link
UniProt P01857 Link_out
Genbank J00228 Link_out
PharmGKB PA452639 Link_out
Drug Product Database 2244016 Link_out
RxList http://www.rxlist.com/cgi/generic3/infliximab.htm Link_out
Drugs.com http://www.drugs.com/cdi/infliximab.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Infliximab Link_out
ATC Codes
  • L04AA12
AHFS Codes
  • 92:00.00
PDB Entries
FDA label show (1.2 MB)
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Tumor necrosis factor

Pharmacological action: yes
Actions: inhibitor

Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin 1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation

Organism class: human
UniProt ID: P01375 Link_out
Gene: TNF Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Mimura T: [Selection of one of the TNF blockers; infliximab and etanercept] Nippon Rinsho. 2007 Jul;65(7):1282-6. Pubmed
  3. Braun J, Baraliakos X, Listing J, Sieper J: Decreased incidence of anterior uveitis in patients with ankylosing spondylitis treated with the anti-tumor necrosis factor agents infliximab and etanercept. Arthritis Rheum. 2005 Aug;52(8):2447-51. Pubmed
  4. Danese S, Sans M, Scaldaferri F, Sgambato A, Rutella S, Cittadini A, Pique JM, Panes J, Katz JA, Gasbarrini A, Fiocchi C: TNF-alpha blockade down-regulates the CD40/CD40L pathway in the mucosal microcirculation: a novel anti-inflammatory mechanism of infliximab in Crohn’s disease. J Immunol. 2006 Feb 15;176(4):2617-24. Pubmed
  5. Magro F, Pereira P, Carneiro F, Veloso FT: Reactive hepatitis in a patient with Crohn’s disease successfully treated with infliximab: does tumor necrosis factor alpha play a role in reactive hepatitis? Inflamm Bowel Dis. 2005 Jan;11(1):88-90. Pubmed
  6. Mori S, Imamura F, Kiyofuji C, Ito K, Koga Y, Honda I, Sugimoto M: Pneumocystis jiroveci pneumonia in a patient with rheumatoid arthritis as a complication of treatment with infliximab, anti-tumor necrosis factor alpha neutralizing antibody. Mod Rheumatol. 2006;16(1):58-62. Pubmed
  7. Maini RN, Feldmann M: How does infliximab work in rheumatoid arthritis? Arthritis Res. 2002;4 Suppl 2:S22-8. Epub 2002 Mar 27. Pubmed
  8. Sapienza MS, Cohen S, Dimarino AJ: Treatment of pyoderma gangrenosum with infliximab in Crohn’s disease. Dig Dis Sci. 2004 Sep;49(9):1454-7. Pubmed
  9. Tobin AM, Kirby B: TNF alpha inhibitors in the treatment of psoriasis and psoriatic arthritis. BioDrugs. 2005;19(1):47-57. Pubmed
  10. Shen C, Assche GV, Colpaert S, Maerten P, Geboes K, Rutgeerts P, Ceuppens JL: Adalimumab induces apoptosis of human monocytes: a comparative study with infliximab and etanercept. Aliment Pharmacol Ther. 2005 Feb 1;21(3):251-8. Pubmed
  11. Popa C, Netea MG, Barrera P, Radstake TR, van Riel PL, Kullberg BJ, Van der Meer JW: Cytokine production of stimulated whole blood cultures in rheumatoid arthritis patients receiving short-term infliximab therapy. Cytokine. 2005 Apr 21;30(2):72-7. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on September 29, 2010 14:34

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.