DT-Web

DB00065 - Infliximab


Identification
Name Infliximab
Accession Number DB00065 (BIOD00004, BTD00004)
Type biotech
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
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 144190.3000
Groups approved
Monoisotopic Weight 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.
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
Protein binding Not Available
Biotransformation 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
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
golimumab Avoid combination with infliximab due to the potential increased immunosuppression of infliximab.
Rilonacept results in increased immunosuppressive effects; increases the risk of infection.
Tofacitinib Avoid combination with infliximab and other anti-TNF drugs due to the potential enhancement of tofacitinib related adverse effects.
Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Food Interactions Not Available

Targets


Tumor necrosis factor
Name Tumor necrosis factor
Gene Name TNF
Pharmacological action yes
Actions inhibitor
References
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
  • Mimura T: [Selection of one of the TNF blockers; infliximab and etanercept] Nippon Rinsho. 2007 Jul;65(7):1282-6. - Pubmed
  • 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
  • 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
  • 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
  • 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
  • Maini RN, Feldmann M: How does infliximab work in rheumatoid arthritis? Arthritis Res. 2002;4 Suppl 2:S22-8. Epub 2002 Mar 27. - Pubmed
  • 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
  • Tobin AM, Kirby B: TNF alpha inhibitors in the treatment of psoriasis and psoriatic arthritis. BioDrugs. 2005;19(1):47-57. - Pubmed
  • 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
  • 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
DTHybrid score 0.6509

Predictions


Id Partner name Gene Name Score
485 cGMP-inhibited 3',5'-cyclic phosphodiesterase A PDE3A 0.0384
1787 Nuclear factor NF-kappa-B p105 subunit NFKB1 0.0335
541 cAMP-specific 3',5'-cyclic phosphodiesterase 4B PDE4B 0.0326
290 Prostaglandin G/H synthase 2 PTGS2 0.0287
1820 Beta-nerve growth factor NGF 0.0274
4200 Cytochrome P450 1A2 CYP1A2 0.0269
3090 Chitosanase csn 0.0265
4149 Nuclear factor NF-kappa-B p100 subunit NFKB2 0.0265
6024 Cytochrome P450 1A1 CYP1A1 0.026
1253 Interferon gamma IFNG 0.023
4512 Cytochrome P450 3A4 CYP3A4 0.0222
2782 Complement C1s subcomponent C1S 0.0213
2232 Interleukin-5 IL5 0.0211
1593 Mucin-2 MUC2 0.021
3815 Complement C1q subcomponent subunit A C1QA 0.0197
3816 Complement C1q subcomponent subunit B C1QB 0.0197
3817 Complement C1q subcomponent subunit C C1QC 0.0196
1102 Low affinity immunoglobulin gamma Fc region receptor III-B FCGR3B 0.0194
3818 Low affinity immunoglobulin gamma Fc region receptor III-A FCGR3A 0.0194
3814 Complement C1r subcomponent C1R 0.0194
3819 Low affinity immunoglobulin gamma Fc region receptor II-a FCGR2A 0.0194
3821 Low affinity immunoglobulin gamma Fc region receptor II-c FCGR2C 0.0194
3820 Low affinity immunoglobulin gamma Fc region receptor II-b FCGR2B 0.0192
784 High affinity immunoglobulin gamma Fc receptor I FCGR1A 0.0186
2112 Toll-like receptor 9 TLR9 0.0185
1588 Multidrug resistance protein 1 ABCB1 0.0185
1517 Beta-3 adrenergic receptor ADRB3 0.0172
65 Matrix metalloproteinase-9 Not Available 0.0171
1123 Eosinophil cationic protein RNASE3 0.0168
6013 Cytochrome P450 2E1 CYP2E1 0.0165
1789 Lymphotoxin-alpha LTA 0.0156
1269 Tumor necrosis factor receptor superfamily member 1B TNFRSF1B 0.0156
778 Cysteinyl leukotriene receptor 1 CYSLTR1 0.0149
6016 Cytochrome P450 2C19 CYP2C19 0.0148
3932 Glutathione S-transferase A2 GSTA2 0.0138
4118 Cytochrome P450 3A5 CYP3A5 0.0134
193 Beta-1 adrenergic receptor ADRB1 0.0126
823 Fibroblast growth factor receptor 2 FGFR2 0.0126
766 Beta-2 adrenergic receptor ADRB2 0.0124
4757 Cytochrome P450 2C9 CYP2C9 0.0122
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0086
4924 Cytochrome P450 2C8 CYP2C8 0.0073
20 Prostaglandin G/H synthase 1 PTGS1 0.0068
4119 Cytochrome P450 2D6 CYP2D6 0.0066
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