Therapeutic Targets Database
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TTD Target ID: TTDS00131

Target Information
NameTumor necrosis factor    
Type of targetSuccessful target    
SynonymsCachectin    
TNF    
TNF alpha    
TNF-a    
TNF-alpha    
TNFalpha    
Tumor necrosis factor ligand superfamily member 2    
Tumor necrosis factor receptor 1    
Tumour necrosis factor    
Tumour necrosis factor alpha    
DiseaseAsthma
[ICD9: 493   ICD10: J45]
[1]
Behcet's disease
[ICD9: 136.1   ICD10: M35.2]
[2]
Chronic inflammatory diseases[3]
Congestive heart failure
[ICD9: 428.0   ICD10: I50]
[4]
Crohn's disease, unspecified
[ICD9: 555   ICD10: K50]
[3]
Heart failure
[ICD9: 428   ICD10: I50]
[5]
Hyperimmunoglobulinemia D[6]
Noninsulin-dependent diabetes mellitus
[ICD9: 250   ICD10: E08-E13]
[7]
Periodic fever syndrome
[ICD9: 780.6   ICD10: R50]
[6]
Rheumatic diseases[8]
Rheumatoid arthritis, unspecified
[ICD9: 710-719, 714   ICD10: M00-M25, M05-M06]
[9]
Rheumatoid arthritis, unspecified
[ICD9: 710-719, 714   ICD10: M00-M25, M05-M06]
[10][11][12]
Solid tumor
[ICD9: 140-199, 210-229   ICD10: C00-C75, C7A, C7B, D10-D36, D3A]
[13]
Drug(s)AdalimumabApprovedRheumatoid arthritis[14]
EtanerceptApprovedRheumatoid arthritis[14][15]
GolimumabApprovedRheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis[16][17]
InfliximabApprovedPsoriasis, Crohn's disease, ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis and ulcerative colitis[18]
LenalidomideApprovedMultiple myeloma[19][20]
PentoxifyllineApprovedIntermittent claudication[21][22]
ThalidomideApprovedMultiple myeloma[23]
CertolizumabPhase IIIRheumatoid arthritis[24]
Certolizumab pegolPhase IIIInflammatory bowel disease[25]
InfliximabPhase IIIAsthma[26]
GolimumabPhase II/IIIInflammatory bowel disease[16][17]
AN0128Phase IIa completedAtopic Dermatitis[27][28][29]
CRx-191Phase IIa completedPsoriasis and Psoriatic Disorders[30]
AN0128Phase I/II completedPsoriasis and Psoriatic Disorders, Acne[27][28][29]
AN0128Phase IIbAtopic Dermatitis, Pediatric[27][28][29]
Certolizumab pegolPhase IIPsoriasis[25]
CytoFabPhase IISevere sepsis & Septic Shock[31]
IP-751Phase IINeuropathic pain[32]
Talactoferrin AlfaPhase IISevere Sepsis, Diabetic foot ulcers[33]
ART621Phase I/IIRheumatoid Arthritis,Psoriasis[17]
TgAAC-94Phase I/IIPsoriatic arthritis, Rheumatoid arthritis[17]
CYT-609Phase ISolid tumors
PirfenidoneDiscontinued in Phase IIIIdiopathic pulmonary fibrosis[34]
RDP-58Discontinued in Phase IIColitis, ulcerative; Crohn's disease; chemotherapy-induced injury, GI; psoriasis; eczema, atopic; multiple sclerosis, general; Barrett's esophagus[35]
RDP58Discontinued in Phase IIUlcerative Colitis, Crohn's Disease[36]
CelastrolPreclinicalMotor neuron disease/amyotropic lateral sclerosis[37]
Genz29155PreclinicalHeart transplantation[38]
BioChemical ClassTransmembrane protein    
PathwayAdipocytokine signaling pathway
Allograft rejection
Alzheimer's disease
Amyotrophic lateral sclerosis (ALS)
Apoptosis
Asthma
Cytokine-cytokine receptor interaction
Fc epsilon RI signaling pathway
Graft-versus-host disease
Hematopoietic cell lineage
MAPK signaling pathway
Natural killer cell mediated cytotoxicity
Systemic lupus erythematosus
T cell receptor signaling pathway
TGF-beta signaling pathway
Toll-like receptor signaling pathway
Type I diabetes mellitus
Type II diabetes mellitus
UniProt IDP01375
PDB Structure1A8M; 1TNF; 2AZ5; 2E7A; 2TUN; 2ZJC; 2ZPX; 3ALQ; 3IT8; 3L9J; 4G3Y; 4TSV; 5TSW.    
FunctionCytokine 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.    
SequenceMSTESMIRDVELAEEALPKKTGGPQGSRRCLFLSLFSFLIVAGATTLFCLLHFGVIGPQR EEFPRDLSLISPLAQAVRSSSRTPSDKPVAHVVANPQAEGQLQWLNRRANALLANGVELR DNQLVVPSEGLYLIYSQVLFKGQGCPSTHVLLTHTISRIAVSYQTKVNLLSAIKSPCQRE TPEGAEAKPWYEPIYLGGVFQLEKGDRLSAEINRPDYLDFAESGQVYFGIIAL
Related US Patent6,162,830
6,376,665
6,379,666
6,419,944
6,423,321
6,432,962
6,455,520
6,489,324
6,495,548
6,495,565
6,541,670
6,555,710
6,566,543
6,566,554
6,635,250
6,642,255
Target ValidationClick to Find Target Validation Information.    
InhibitorAN0128[27][28][29]
ART621[17]
BAICALEIN[39]
CRx-191[30]
Certolizumab[24]
Genz29155[38]
IK-682[40]
IP-751[32]
Isopropyl Alcohol[41]
Lenalidomide[19][20]
PKF-241-466[42]
PKF-242-484,   TNF-484[42]
Pirfenidone[34]
RDP-58[35]
RDP58[36]
SB-203580[43]
Talactoferrin Alfa[33]
TgAAC-94[17]
Thalidomide[23]
Y-39041[44]
AntibodyAdalimumab[14]
Certolizumab pegol[25]
CytoFab[31]
Etanercept[14][15]
Golimumab[16][17]
Infliximab[18]
Infliximab[26]
Monoclonal antibodies[45]
Pentoxifylline[21][22]
SuppressorCelastrol[37]
MultitargetCRx-191[30]
Pirfenidone[34]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1Tumour necrosis factor-alpha: the role of this multifunctional cytokine in asthma. Immunol Cell Biol. 2001 Apr;79(2):132-40. To Reference
Ref 2Beh?et's disease: a new target for anti-tumour necrosis factor treatment. Ann Rheum Dis. 2002 Nov;61 Suppl 2:ii51-3. To Reference
Ref 3Tumour necrosis factor as a therapeutic target in rheumatoid arthritis and other chronic inflammatory diseases: the clinical experience with infliximab (REMICADE). Int J Clin Pract. 2001 Apr;55(3):211-6. To Reference
Ref 4Tumour necrosis factor as a potential target for the treatment of congestive heart failure. Pharmacol Res. 1999 Aug;40(2):91. To Reference
Ref 5Tumor necrosis factor-alpha blockade as a therapeutic strategy in heart failure (RENEWAL and ATTACH): unsuccessful, to be specific. J Card Fail. 2002 Dec;8(6):365-8. To Reference
Ref 6Favorable preliminary experience with etanercept in two patients with the hyperimmunoglobulinemia D and periodic fever syndrome. Arthritis Rheum. 2003 Sep;48(9):2645-51. To Reference
Ref 7Inhibition of insulin receptor signaling by TNF: potential role in obesity and non-insulin-dependent diabetes mellitus. Cytokine Growth Factor Rev. 1996 Aug;7(2):161-73. To Reference
Ref 8Infliximab treatment for rheumatic disease: clinical and radiological efficacy. Ann Rheum Dis. 2002 Nov;61 Suppl 2:ii67-9. To Reference
Ref 9Tumor necrosis factor-alpha antagonists for the treatment of rheumatic diseases. Curr Opin Rheumatol. 2002 May;14(3):204-11. To Reference
Ref 10Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor alpha. Arthritis Rheum. 1993 Dec;36(12):1681-90. To Reference
Ref 11Identification and characterization of 4-[[4-(2-butynyloxy)phenyl]sulfonyl]-N-hydroxy-2,2-dimethyl-(3S)thiomorpholinecarboxamide (TMI-1), a novel dual tumor necrosis factor-alpha-converting enzyme/matrix metalloprotease inhibitor for the treatment of rheumatoid arthritis. J Pharmacol Exp Ther. 2004 Apr;309(1):348-55. Epub 2004 Jan 12. To Reference
Ref 12Common and uncommon features of rheumatoid arthritis and chronic obstructive pulmonary disease: clues to a future therapy. Curr Drug Targets Immune Endocr Metabol Disord. 2004 Jun;4(2):85-92. To Reference
Ref 13Tumour necrosis factor alpha: a potential target for the therapy of solid tumours. Lancet Oncol. 2003 Sep;4(9):565-73. To Reference
Ref 14Adalimumab for psoriasis patients who are non-responders to etanercept: open-label prospective evaluation. J Eur Acad Dermatol Venereol. 2009 Jul 1. [Epub ahead of print] To Reference
Ref 15TNF alpha Inhibition as Treatment Modality for Certain Rheumatologic and Gastrointestinal Diseases. Endocr Metab Immune Disord Drug Targets. 2009 Sep 1. [Epub ahead of print] To Reference
Ref 16Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92. To Reference
Ref 17Emerging drugs for psoriasis. Expert Opin Emerg Drugs. 2009 Mar;14(1):145-63. To Reference
Ref 18Drug insight: tumor necrosis factor-converting enzyme as a pharmaceutical target for rheumatoid arthritis. Nat Clin Pract Rheumatol. 2008 Jun;4(6):300-9. Epub 2008 Apr 15. To Reference
Ref 19Thalidomide and thalidomide analogues for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD007351. To Reference
Ref 20The thalidomide saga. Int J Biochem Cell Biol. 2007;39(7-8):1489-99. Epub 2007 Jan 30. To Reference
Ref 21Targeted therapies in myelodysplastic syndromes: ASH 2003 review. Semin Hematol. 2004 Apr;41(2 Suppl 4):13-20. To Reference
Ref 22Tumor necrosis factor alpha in the pathogenesis of cerebral malaria. Cell Mol Life Sci. 2003 Aug;60(8):1623-35. To Reference
Ref 23Efficacy of different thalidomide regimens for patients with multiple myeloma and its relationship with TNF-alpha level. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2008 Dec;16(6):1312-5. To Reference
Ref 24Emerging drugs for rheumatoid arthritis. Expert Opin Emerg Drugs. 2008 Mar;13(1):175-96. To Reference
Ref 25Emerging drugs to treat Crohn's disease. Expert Opin Emerg Drugs. 2007 Mar;12(1):49-59. To Reference
Ref 26Emerging drugs for asthma. Expert Opin Emerg Drugs. 2008 Dec;13(4):643-53. To Reference
Ref 27Inhibition of experimental periodontitis by a topical boron-based antimicrobial. J Dent Res. 2008 Feb;87(2):148-52. To Reference
Ref 28Identification of a novel boron-containing antibacterial agent (AN0128) with anti-inflammatory activity, for the potential treatment of cutaneous diseases. Bioorg Med Chem Lett. 2006 Dec 1;16(23):5963-7. Epub 2006 Sep 25. To Reference
Ref 29Anacor Announces Positive Results From Phase 2 Trial Of Novel Anti-Inflammatory Agent For The Treatment Of Atopic Dermatitis. Anacor Pharmaceuticals. 2006 To Reference
Ref 30CombinatoRx Drug Candidate CRx-191 Demonstrates Positive Phase 2 Results In Psoriasis. CombinatoRx. 2008 To Reference
Ref 31AstraZeneca. Product Development Pipeline. January 29 2009. To Reference
Ref 32Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26. To Reference
Ref 33Emerging drugs for diabetic foot ulcers. Expert Opin Emerg Drugs. 2006 Nov;11(4):709-24. To Reference
Ref 34Current and emerging drugs for idiopathic pulmonary fibrosis. Expert Opin Emerg Drugs. 2007 Nov;12(4):627-46. To Reference
Ref 35Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91. To Reference
Ref 36RDP58, a locally active TNF inhibitor, is effective in the dextran sulphate mouse model of chronic colitis. Inflamm Res. 2002 Nov;51(11):522-31. To Reference
Ref 37Emerging disease-modifying therapies for the treatment of motor neuron disease/amyotropic lateral sclerosis. Expert Opin Emerg Drugs. 2007 May;12(2):229-52. To Reference
Ref 38New developments in immunosuppressive therapy for heart transplantation. Expert Opin Emerg Drugs. 2009 Mar;14(1):1-21. To Reference
Ref 39Bioorg Med Chem Lett. 2010 Nov 1;20(21):6195-8. Epub 2010 Sep 16.Discovery of the inhibitors of tumor necrosis factor alpha with structure-based virtual screening. To Reference
Ref 40J Med Chem. 2002 Nov 7;45(23):4954-7.Discovery of gamma-lactam hydroxamic acids as selective inhibitors of tumor necrosis factor alpha converting enzyme: design, synthesis, and structure-activity relationships. To Reference
Ref 41Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. To Reference
Ref 42J Med Chem. 2002 May 23;45(11):2289-93.Beta-aryl-succinic acid hydroxamates as dual inhibitors of matrix metalloproteinases and tumor necrosis factor alpha converting enzyme. To Reference
Ref 43J Med Chem. 2005 Jan 27;48(2):414-26.Identification of novel p38alpha MAP kinase inhibitors using fragment-based lead generation. To Reference
Ref 44A novel anti-rheumatic drug suppresses tumor necrosis factor-alpha and augments interleukin-10 in adjuvant arthritic rats. Eur J Pharmacol. 2000 Dec 15;409(3):331-5. To Reference
Ref 45Treatment of rheumatoid arthritis: new therapeutic approaches with biological agents. Curr Drug Targets Immune Endocr Metabol Disord. 2001 May;1(1):45-65. To Reference



 

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