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Showing drug card for Infliximab (DB00065)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-05-26 13:52:36
Primary Accession Number DB00065
Secondary Accession Number
  • BIOD00004
  • BTD00004
Name Infliximab
Drug Type
  • Approved
  • 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
Synonyms
  1. Ig gamma-1 chain C region
Brand Names
  1. Remicade (Centocor Inc)
Brand Mixtures Not Available
Chemical IUPAC Name Chimeric mouse/human anti-TNF-alpha antibody (cA2)
Chemical Formula C6428H9912N1694O1987S46
Chemical Structure Structure
Protein Sequence(s) Not Available
CAS Registry Number 170277-31-3
InChI Identifier Not Available
InChI Key Not Available
KEGG Drug Not Available
KEGG Compound Not Available
PubChem Compound Not Available
PubChem Substance Not Available
ChEBI ID Not Available
PharmGKB ID PA452639 Link Image
HET ID Not Available
GenBank ID J00228 Link Image
Drug ID Number [DIN] 02244016 Link Image
RxList Link http://www.rxlist.com/cgi/generic3/infliximab.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Infliximab Link Image
FDA Label
Material Safety Data Sheet (MSDS) Not Available
Synthesis Reference U.S. patent 6,015,557, Nagahira K, Fukuda Y, Oyama Y, Kurihara T, Nasu T, Kawashima H, Noguchi C, Oikawa S, Nakanishi T. Humanization of a mouse neutralizing monoclonal antibody against tumor necrosis factor-alpha (TNF-alpha). J Immunol Methods. 1999 Jan 1;222(1-2):83-92.) 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.
Average Molecular Weight 144190.3000
Monoisotopic Molecular Weight Not Available
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 Water Solubility Not Available Source: PhysProp
Predicted Water Solubility Not Available Calculated using ALOGPS
Experimental LogP/Hydrophobicity -0.441 Source: PhysProp
Predicted LogP Not Available Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS Not Available Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point 8.25
Mass Spectrum Not Available
MOL File Not Available
SDF File Not Available
PDB File Not Available
Experimental PDB ID 1IGT Link Image
Experimental PDB File Show
Experimental PDB Structure
Isomeric SMILES Not Available
Canonical SMILES Not Available
Drug Category
  • Immunomodulatory Agents
  • Immunosuppressive Agents
ATC Codes
AHFS Codes
  • 92:00.00
Indication For treatment of Crohn's disease, psoriasis, rheumatoid arthitis and ankylosing spondylitis
Pharmacology Used in the treatment of auto-immune disorders such as Crohn's disease and rheumatoid arthritis. Infliximab 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
Absorption Not Available
Toxicity 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
Half Life 9.5 days
Dosage Forms
Form Route
Powder, for solution Intravenous
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions Not Available
Food Interactions Not Available
Pathways Not Available
General References
  1. 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 Link Image]
  2. Hanauer SB: Crohn's disease: step up or top down therapy. Best Pract Res Clin Gastroenterol. 2003 Feb;17(1):131-7. [PubMed Link Image]
  3. 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 Link Image]
  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 Link Image]
  5. 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 Link Image]
  6. Drugs.com Link Image
  7. Wikipedia Link Image
  8. RxList Link Image
Organisms Affected
  • Humans and other mammals
Targets
  1. Tumor necrosis factor
  2. Tumor necrosis factor receptor superfamily member 1B
  3. Lymphotoxin-beta
Drug Target 1 [top]
Target 1 ID 777
Target 1 Name Tumor necrosis factor
Target 1 Synonyms
  1. Cachectin
  2. TNF-a
  3. TNF-alpha
  4. Tumor necrosis factor ligand superfamily member 2
  5. Tumor necrosis factor precursor
Target 1 Gene Name TNF
Target 1 Protein Sequence >Tumor necrosis factor precursor 
MSTESMIRDVELAEEALPKKTGGPQGSRRCLFLSLFSFLIVAGATTLFCLLHFGVIGPQR
EEFPRDLSLISPLAQAVRSSSRTPSDKPVAHVVANPQAEGQLQWLNRRANALLANGVELR
DNQLVVPSEGLYLIYSQVLFKGQGCPSTHVLLTHTISRIAVSYQTKVNLLSAIKSPCQRE
TPEGAEAKPWYEPIYLGGVFQLEKGDRLSAEINRPDYLDFAESGQVYFGIIAL
Target 1 Number of Residues 236
Target 1 Molecular Weight 25645
Target 1 Theoretical pI 6.92
Target 1 GO Classification
Function
signal transducer activity
receptor binding
cytokine activity
tumor necrosis factor receptor binding
Process
response to stimulus
response to biotic stimulus
defense response
immune response
Component
cell
membrane
Target 1 General Function Involved in tumor necrosis factor receptor binding
Target 1 Specific Function 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
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 36-56
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 339741 Link Image
Target 1 UniProtKB/Swiss-Prot ID P01375 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name TNFA_HUMAN Link Image
Target 1 PDB ID 1A8M Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Cell membrane
  • single-pass type II membrane protein. Processed form:Secreted protein. Also exists as
Target 1 Gene Sequence >702 bp 
ATGAGCACTGAAAGCATGATCCGGGACGTGGAGCTGGCCGAGGAGGCGCTCCCCAAGAAG
ACAGGGGGGCCCCAGGGCTCCAGGCGGTGCTTGTTCCTCAGCCTCTTCTCCTTCCTGATC
GTGGCAGGCGCCACCACGCTCTTCTGCCTGCTGCACTTTGGAGTGATCGGCCCCCAGAGG
GAAGAGTTCCCCAGGGACCTCTCTCTAATCAGCCCTCTGGCCCAGGCAGTCAGATCATCT
TCTCGAACCCCGAGTGACAAGCCTGTAGCCCATGTTGTAGCAAACCCTCAAGCTGAGGGG
CAGCTCCAGTGGCTGAACCGCCGGGCCAATGCCCTCCTGGCCAATGGCGTGGAGCTGAGA
GATAACCAGCTGGTGGTGCCATCAGAGGGCCTGTACCTCATCTACTCCCAGGTCCTCTTC
AAGGGCCAAGGCTGCCCCTCCACCCATGTGCTCCTCACCCACACCATCAGCCGCATCGCC
GTCTCCTACCAGACCAAGGTCAACCTCCTCTCTGCCATCAAGAGCCCCTGCCAGAGGGAG
ACCCCAGAGGGGGCTGAGGCCAAGCCCTGGTATGAGCCCATCTATCTGGGAGGGGTCTTC
CAGCTGGAGAAGGGTGACCGACTCAGCGCTGAGATCAATCGGCCCGACTATCTCGACTTT
GCCGAGTCTGGGCAGGTCTACTTTGGGATCATTGCCCTGTGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID TNF Link Image
Target 1 GenAtlas ID TNF Link Image
Target 1 HGNC ID HGNC:11892 Link Image
Target 1 Chromosome Location 6
Target 1 Locus 6p21.3
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Neville MJ, Campbell RD: A new member of the Ig superfamily and a V-ATPase G subunit are among the predicted products of novel genes close to the TNF locus in the human MHC. J Immunol. 1999 Apr 15;162(8):4745-54. [PubMed Link Image]
  2. Watts AD, Hunt NH, Wanigasekara Y, Bloomfield G, Wallach D, Roufogalis BD, Chaudhri G: A casein kinase I motif present in the cytoplasmic domain of members of the tumour necrosis factor ligand family is implicated in 'reverse signalling'. EMBO J. 1999 Apr 15;18(8):2119-26. [PubMed Link Image]
  3. Stevenson FT, Bursten SL, Locksley RM, Lovett DH: Myristyl acylation of the tumor necrosis factor alpha precursor on specific lysine residues. J Exp Med. 1992 Oct 1;176(4):1053-62. [PubMed Link Image]
  4. Jones EY, Stuart DI, Walker NP: The structure of tumour necrosis factor--implications for biological function. J Cell Sci Suppl. 1990;13:11-8. [PubMed Link Image]
  5. Van Ostade X, Tavernier J, Prange T, Fiers W: Localization of the active site of human tumour necrosis factor (hTNF) by mutational analysis. EMBO J. 1991 Apr;10(4):827-36. [PubMed Link Image]
  6. Eck MJ, Sprang SR: The structure of tumor necrosis factor-alpha at 2.6 A resolution. Implications for receptor binding. J Biol Chem. 1989 Oct 15;264(29):17595-605. [PubMed Link Image]
  7. Jones EY, Stuart DI, Walker NP: Structure of tumour necrosis factor. Nature. 1989 Mar 16;338(6212):225-8. [PubMed Link Image]
  8. Nedwin GE, Naylor SL, Sakaguchi AY, Smith D, Jarrett-Nedwin J, Pennica D, Goeddel DV, Gray PW: Human lymphotoxin and tumor necrosis factor genes: structure, homology and chromosomal localization. Nucleic Acids Res. 1985 Sep 11;13(17):6361-73. [PubMed Link Image]
  9. Nedospasov SA, Shakhov AN, Turetskaya RL, Mett VA, Azizov MM, Georgiev GP, Korobko VG, Dobrynin VN, Filippov SA, Bystrov NS, et al.: Tandem arrangement of genes coding for tumor necrosis factor (TNF-alpha) and lymphotoxin (TNF-beta) in the human genome. Cold Spring Harb Symp Quant Biol. 1986;51 Pt 1:611-24. [PubMed Link Image]
  10. Wang AM, Creasey AA, Ladner MB, Lin LS, Strickler J, Van Arsdell JN, Yamamoto R, Mark DF: Molecular cloning of the complementary DNA for human tumor necrosis factor. Science. 1985 Apr 12;228(4696):149-54. [PubMed Link Image]
  11. 3883195 Shirai T, Yamaguchi H, Ito H, Todd CW, Wallace RB: Cloning and expression in Escherichia coli of the gene for human tumour necrosis factor. Nature. 1985 Feb 28-Mar 6;313(6005):803-6.
  12. 3932069 Marmenout A, Fransen L, Tavernier J, Van der Heyden J, Tizard R, Kawashima E, Shaw A, Johnson MJ, Semon D, Muller R, et al.: Molecular cloning and expression of human tumor necrosis factor and comparison with mouse tumor necrosis factor. Eur J Biochem. 1985 Nov 4;152(3):515-22.
  13. 6392892 Pennica D, Nedwin GE, Hayflick JS, Seeburg PH, Derynck R, Palladino MA, Kohr WJ, Aggarwal BB, Goeddel DV: Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature. 1984 Dec 20-1985 Jan 2;312(5996):724-9.
  14. 8499947 Iris FJ, Bougueleret L, Prieur S, Caterina D, Primas G, Perrot V, Jurka J, Rodriguez-Tome P, Claverie JM, Dausset J, et al.: Dense Alu clustering and a potential new member of the NF kappa B family within a 90 kilobase HLA class III segment. Nat Genet. 1993 Feb;3(2):137-45.
  15. 8597870 Pocsik E, Duda E, Wallach D: Phosphorylation of the 26 kDa TNF precursor in monocytic cells and in transfected HeLa cells. J Inflamm. 1995;45(3):152-60.
  16. 9034191 Moss ML, Jin SL, Milla ME, Bickett DM, Burkhart W, Carter HL, Chen WJ, Clay WC, Didsbury JR, Hassler D, Hoffman CR, Kost TA, Lambert MH, Leesnitzer MA, McCauley P, McGeehan G, Mitchell J, Moyer M, Pahel G, Rocque W, Overton LK, Schoenen F, Seaton T, Su JL, Becherer JD, et al.: Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha. Nature. 1997 Feb 20;385(6618):733-6.
  17. 9442056 Cha SS, Kim JS, Cho HS, Shin NK, Jeong W, Shin HC, Kim YJ, Hahn JH, Oh BH: High resolution crystal structure of a human tumor necrosis factor-alpha mutant with low systemic toxicity. J Biol Chem. 1998 Jan 23;273(4):2153-60.
  18. 9488135 Reed C, Fu ZQ, Wu J, Xue YN, Harrison RW, Chen MJ, Weber IT: Crystal structure of TNF-alpha mutant R31D with greater affinity for receptor R1 compared with R2. Protein Eng. 1997 Oct;10(10):1101-7.
Target 1 Drug References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
  2. 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 Link Image]
  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 Link Image]
  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 Link Image]
  5. 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 Link Image]
  6. Mimura T: [Selection of one of the TNF blockers; infliximab and etanercept] Nippon Rinsho. 2007 Jul;65(7):1282-6. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 1269
Target 2 Name Tumor necrosis factor receptor superfamily member 1B
Target 2 Synonyms
  1. CD120b antigen
  2. Etanercept
  3. TNF-R2
  4. Tumor necrosis factor receptor 2
  5. Tumor necrosis factor receptor superfamily member 1B precursor
  6. Tumor necrosis factor receptor type II
  7. p75
  8. p80 TNF-alpha receptor
Target 2 Gene Name TNFRSF1B
Target 2 Protein Sequence >Tumor necrosis factor receptor superfamily member 1B precursor 
MAPVAVWAALAVGLELWAAAHALPAQVAFTPYAPEPGSTCRLREYYDQTAQMCCSKCSPG
QHAKVFCTKTSDTVCDSCEDSTYTQLWNWVPECLSCGSRCSSDQVETQACTREQNRICTC
RPGWYCALSKQEGCRLCAPLRKCRPGFGVARPGTETSDVVCKPCAPGTFSNTTSSTDICR
PHQICNVVAIPGNASMDAVCTSTSPTRSMAPGAVHLPQPVSTRSQHTQPTPEPSTAPSTS
FLLPMGPSPPAEGSTGDFALPVGLIVGVTALGLLIIGVVNCVIMTQVKKKPLCLQREAKV
PHLPADKARGTQGPEQQHLLITAPSSSSSSLESSASALDRRAPTRNQPQAPGVEASGAGE
ARASTGSSDSSPGGHGTQVNVTCIVNVCSSSDHSSQCSSQASSTMGDTDSSPSESPKDEQ
VPFSKEECAFRSQLETPETLLGSTEEKPLPLGVPDAGMKPS
Target 2 Number of Residues 468
Target 2 Molecular Weight 48291
Target 2 Theoretical pI 6.22
Target 2 GO Classification
Function
signal transducer activity
receptor activity
transmembrane receptor activity
death receptor activity
tumor necrosis factor receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
cytokine and chemokine mediated signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 2 General Function Involved in tumor necrosis factor receptor activity
Target 2 Specific Function Receptor with high affinity for TNFSF2/TNF-alpha and approximately 5-fold lower affinity for homotrimeric TNFSF1/lymphotoxin-alpha. The TRAF1/TRAF2 complex recruits the apoptotic suppressors BIRC2 and BIRC3 to TNFRSF1B/TNFR2. This receptor mediates most of the metabolic effects of TNF-alpha. Isoform 2 blocks TNF-alpha-induced apoptosis, which suggests that it regulates TNF-alpha function by antagonizing its biological activity
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • 1-22
Target 2 Transmembrane Regions
  • 258-287
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 189186 Link Image
Target 2 UniProtKB/Swiss-Prot ID P20333 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name TNR1B_HUMAN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Isoform 1:Cell membrane
  • single-pass type I membrane protein. Isoform 2:Secreted protein. TBP-II:Sec
Target 2 Gene Sequence >1386 bp 
ATGGCGCCCGTCGCCGTCTGGGCCGCGCTGGCCGTCGGACTGGAGCTCTGGGCTGCGGCG
CACGCCTTGCCCGCCCAGGTGGCATTTACACCCTACGCCCCGGAGCCCGGGAGCACATGC
CGGCTCAGAGAATACTATGACCAGACAGCTCAGATGTGCTGCAGCAAATGCTCGCCGGGC
CAACATGCAAAAGTCTTCTGTACCAAGACCTCGGACACCGTGTGTGACTCCTGTGAGGAC
AGCACATACACCCAGCTCTGGAACTGGGTTCCCGAGTGCTTGAGCTGTGGCTCCCGCTGT
AGCTCTGACCAGGTGGAAACTCAAGCCTGCACTCGGGAACAGAACCGCATCTGCACCTGC
AGGCCCGGCTGGTACTGCGCGCTGAGCAAGCAGGAGGGGTGCCGGCTGTGCGCGCCGCTG
CGCAAGTGCCGCCCGGGCTTCGGCGTGGCCAGACCAGGAACTGAAACATCAGACGTGGTG
TGCAAGCCCTGTGCCCCGGGGACGTTCTCCAACACGACTTCATCCACGGATATTTGCAGG
CCCCACCAGATCTGTAACGTGGTGGCCATCCCTGGGAATGCAAGCATGGATGCAGTCTGC
ACGTCCACGTCCCCCACCCGGAGTATGGCCCCAGGGGCAGTACACTTACCCCAGCCAGTG
TCCACACGATCCCAACACACGCAGCCAACTCCAGAACCCAGCACTGCTCCAAGCACCTCC
TTCCTGCTCCCAATGGGCCCCAGCCCCCCAGCTGAAGGGAGCACTGGCGACTTCGCTCTT
CCAGTTGGACTGATTGTGGGTGTGACAGCCTTGGGTCTACTAATAATAGGAGTGGTGAAC
TGTGTCATCATGACCCAGGTGAAAAAGAAGCCCTTGTGCCTGCAGAGAGAAGCCAAGGTG
CCTCACTTGCCTGCCGATAAGGCCCGGGGTACACAGGGCCCCGAGCAGCAGCACCTGCTG
ATCACAGCGCCGAGCTCCAGCAGCAGCTCCCTGGAGAGCTCGGCCAGTGCGTTGGACAGA
AGGGCGCCCACTCGGAACCAGCCACAGGCACCAGGCGTGGAGGCCAGTGGGGCCGGGGAG
GCCCGGGCCAGCACCGGGAGCTCAGATTCTTCCCCTGGTGGCCATGGGACCCAGGTCAAT
GTCACCTGCATCGTGAACGTCTGTAGCAGCTCTGACCACAGCTCACAGTGCTCCTCCCAA
GCCAGCTCCACAATGGGAGACACAGATTCCAGCCCCTCGGAGTCCCCGAAGGACGAGCAG
GTCCCCTTCTCCAAGGAGGAATGTGCCTTTCGGTCACAGCTGGAGACGCCAGAGACCCTG
CTGGGGAGCACCGAAGAGAAGCCCCTGCCCCTTGGAGTGCCTGATGCTGGGATGAAGCCC
AGTTAA
Target 2 GenBank Gene ID
Target 2 GeneCard ID TNFRSF1B Link Image
Target 2 GenAtlas ID TNFRSF1B Link Image
Target 2 HGNC ID HGNC:11917 Link Image
Target 2 Chromosome Location 1
Target 2 Locus 1p36.3-p36.2
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Park YC, Burkitt V, Villa AR, Tong L, Wu H: Structural basis for self-association and receptor recognition of human TRAF2. Nature. 1999 Apr 8;398(6727):533-8. [PubMed Link Image]
  2. Tsuchiya N, Komata T, Matsushita M, Ohashi J, Tokunaga K: New single nucleotide polymorphisms in the coding region of human TNFR2: association with systemic lupus erythematosus. Genes Immun. 2000 Dec;1(8):501-3. [PubMed Link Image]
  3. Morita C, Horiuchi T, Tsukamoto H, Hatta N, Kikuchi Y, Arinobu Y, Otsuka T, Sawabe T, Harashima S, Nagasawa K, Niho Y: Association of tumor necrosis factor receptor type II polymorphism 196R with Systemic lupus erythematosus in the Japanese: molecular and functional analysis. Arthritis Rheum. 2001 Dec;44(12):2819-27. [PubMed Link Image]
  4. Peral B, San Millan JL, Castello R, Moghetti P, Escobar-Morreale HF: Comment: the methionine 196 arginine polymorphism in exon 6 of the TNF receptor 2 gene (TNFRSF1B) is associated with the polycystic ovary syndrome and hyperandrogenism. J Clin Endocrinol Metab. 2002 Aug;87(8):3977-83. [PubMed Link Image]
  5. Pennica D, Lam VT, Mize NK, Weber RF, Lewis M, Fendly BM, Lipari MT, Goeddel DV: Biochemical properties of the 75-kDa tumor necrosis factor receptor. Characterization of ligand binding, internalization, and receptor phosphorylation. J Biol Chem. 1992 Oct 15;267(29):21172-8. [PubMed Link Image]
  6. Dembic Z, Loetscher H, Gubler U, Pan YC, Lahm HW, Gentz R, Brockhaus M, Lesslauer W: Two human TNF receptors have similar extracellular, but distinct intracellular, domain sequences. Cytokine. 1990 Jul;2(4):231-7. [PubMed Link Image]
  7. Engelmann H, Novick D, Wallach D: Two tumor necrosis factor-binding proteins purified from human urine. Evidence for immunological cross-reactivity with cell surface tumor necrosis factor receptors. J Biol Chem. 1990 Jan 25;265(3):1531-6. [PubMed Link Image]
  8. Smith CA, Davis T, Anderson D, Solam L, Beckmann MP, Jerzy R, Dower SK, Cosman D, Goodwin RG: A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins. Science. 1990 May 25;248(4958):1019-23. [PubMed Link Image]
  9. Heller RA, Song K, Onasch MA, Fischer WH, Chang D, Ringold GM: Complementary DNA cloning of a receptor for tumor necrosis factor and demonstration of a shed form of the receptor. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6151-5. [PubMed Link Image]
  10. Kohno T, Brewer MT, Baker SL, Schwartz PE, King MW, Hale KK, Squires CH, Thompson RC, Vannice JL: A second tumor necrosis factor receptor gene product can shed a naturally occurring tumor necrosis factor inhibitor. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8331-5. [PubMed Link Image]
  11. 2173696 Loetscher H, Schlaeger EJ, Lahm HW, Pan YC, Lesslauer W, Brockhaus M: Purification and partial amino acid sequence analysis of two distinct tumor necrosis factor receptors from HL60 cells. J Biol Chem. 1990 Nov 25;265(33):20131-8.
  12. 8069916 Rothe M, Wong SC, Henzel WJ, Goeddel DV: A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor. Cell. 1994 Aug 26;78(4):681-92.
  13. 8661109 Beltinger CP, White PS, Maris JM, Sulman EP, Jensen SJ, LePaslier D, Stallard BJ, Goeddel DV, de Sauvage FJ, Brodeur GM: Physical mapping and genomic structure of the human TNFR2 gene. Genomics. 1996 Jul 1;35(1):94-100.
Target 2 Drug References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
Drug Target 3 [top]
Target 3 ID 2163
Target 3 Name Lymphotoxin-beta
Target 3 Synonyms
  1. LT-beta
  2. TNF-C
  3. Tumor necrosis factor C
  4. Tumor necrosis factor ligand superfamily member 3
Target 3 Gene Name LTB
Target 3 Protein Sequence >Lymphotoxin-beta 
MGALGLEGRGGRLQGRGSLLLAVAGATSLVTLLLAVPITVLAVLALVPQDQGGLVTETAD
PGAQAQQGLGFQKLPEEEPETDLSPGLPAAHLIGAPLKGQGLGWETTKEQAFLTSGTQFS
DAEGLALPQDGLYYLYCLVGYRGRAPPGGGDPQGRSVTLRSSLYRAGGAYGPGTPELLLE
GAETVTPVLDPARRQGYGPLWYTSVGFGGLVQLRRGERVYVNISHPDMVDFARGKTFFGA
VMVG
Target 3 Number of Residues 248
Target 3 Molecular Weight 25390
Target 3 Theoretical pI 5.02
Target 3 GO Classification
Function
signal transducer activity
receptor binding
cytokine activity
tumor necrosis factor receptor binding
Process
response to stimulus
response to biotic stimulus
defense response
immune response
Component
cell
membrane
Target 3 General Function Involved in tumor necrosis factor receptor binding
Target 3 Specific Function Cytokine that binds to LTBR/TNFRSF3. May play a specific role in immune response regulation. Provides the membrane anchor for the attachment of the heterotrimeric complex to the cell surface. Isoform 2 is probably non-functional
Target 3 Pathways Not Available
Target 3 Reactions Not Available
Target 3 Pfam Domain Function
Target 3 Signals
  • None
Target 3 Transmembrane Regions
  • 19-48
Target 3 Essentiality Non-Essential
Target 3 GenBank ID Protein 292279 Link Image
Target 3 UniProtKB/Swiss-Prot ID Q06643 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name TNFC_HUMAN Link Image
Target 3 PDB ID Not Available
Target 3 Cellular Location
  • Membrane
  • single-pass type II membrane protein (Potential)
Target 3 Gene Sequence >735 bp 
ATGGGGGCACTGGGGCTGGAGGGCAGGGGTGGGAGGCTCCAGGGGAGGGGTTCCCTCCTG
CTAGCTGTGGCAGGAGCCACTTCTCTGGTGACCTTGTTGCTGGCGGTGCCTATCACTGTC
CTGGCTGTGCTGGCCTTAGTGCCCCAGGATCAGGGAGGACTGGTAACGGAGACGGCCGAC
CCCGGGGCACAGGCCCAGCAAGGACTGGGGTTTCAGAAGCTGCCAGAGGAGGAGCCAGAA
ACAGATCTCAGCCCCGGGCTCCCAGCTGCCCACCTCATAGGCGCTCCGCTGAAGGGGCAG
GGGCTAGGCTGGGAGACGACGAAGGAACAGGCGTTTCTGACGAGCGGGACGCAGTTCTCG
GACGCCGAGGGGCTGGCGCTCCCGCAGGACGGCCTCTATTACCTCTACTGTCTCGTCGGC
TACCGGGGCCGGGCGCCCCCTGGCGGCGGGGACCCCCAGGGCCGCTCGGTCACGCTGCGC
AGCTCTCTGTACCGGGCGGGGGGCGCCTACGGGCCGGGCACTCCCGAGCTGCTGCTCGAG
GGCGCCGAGACGGTGACTCCAGTGCTGGACCCGGCCAGGAGACAAGGGTACGGGCCTCTC
TGGTACACGAGCGTGGGGTTCGGCGGCCTGGTGCAGCTCCGGAGGGGCGAGAGGGTGTAC
GTCAACATCAGTCACCCCGATATGGTGGACTTCGCGAGAGGGAAGACCTTCTTTGGGGCC
GTGATGGTGGGGTGA
Target 3 GenBank Gene ID
Target 3 GeneCard ID LTB Link Image
Target 3 GenAtlas ID LTB Link Image
Target 3 HGNC ID HGNC:6711 Link Image
Target 3 Chromosome Location 6
Target 3 Locus 6p21.3
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Neville MJ, Campbell RD: A new member of the Ig superfamily and a V-ATPase G subunit are among the predicted products of novel genes close to the TNF locus in the human MHC. J Immunol. 1999 Apr 15;162(8):4745-54. [PubMed Link Image]
  2. Browning JL, Ngam-ek A, Lawton P, DeMarinis J, Tizard R, Chow EP, Hession C, O'Brine-Greco B, Foley SF, Ware CF: Lymphotoxin beta, a novel member of the TNF family that forms a heteromeric complex with lymphotoxin on the cell surface. Cell. 1993 Mar 26;72(6):847-56. [PubMed Link Image]
  3. Warzocha K, Renard N, Charlot C, Bienvenu J, Coiffier B, Salles G: Identification of two lymphotoxin beta isoforms expressed in human lymphoid cell lines and non-Hodgkin's lymphomas. Biochem Biophys Res Commun. 1997 Sep 18;238(2):273-6. [PubMed Link Image]
Target 3 Drug References
  1. Maini RN, Feldmann M: How does infliximab work in rheumatoid arthritis? Arthritis Res. 2002;4 Suppl 2:S22-8. Epub 2002 Mar 27. [PubMed Link Image]
  2. 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 Link Image]
  3. Tobin AM, Kirby B: TNF alpha inhibitors in the treatment of psoriasis and psoriatic arthritis. BioDrugs. 2005;19(1):47-57. [PubMed Link Image]
  4. 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 Link Image]
  5. 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 Link Image]

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.