Target Information

Target General Infomation
Target ID
T20178
Former ID
TTDS00131
Target Name
Tumor necrosis factor
Gene Name
TNF
Synonyms
Cachectin; 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; TNF
Target Type
Successful
Disease Arthritis [ICD9: 710-719; ICD10: M00-M25]
Asthma [ICD10: J45]
Atopic dermatitis; Psoriatic disorder [ICD9:691.8, 692.9, 696; ICD10: L00-L99, L40]
Allergic rhinitis [ICD9: 472.0, 477, 995.3; ICD10: J00, J30, J31.0, T78.4]
Autoimmune diabetes [ICD10: E08-E13]
Crohn's disease; Ulcerative colitis; Rheumatoid arthritis; Ankylosing spondylitis; Psoriatic arthritis; Plaque psoriasis [ICD10: K50.0, K51.90, M05.9, M45.3, L40.52, L40]
Crohn's disease [ICD9: 555; ICD10: K50]
Colitis [ICD9: 556.9; ICD10: K50-K52]
Diarrhea [ICD9: 787.91; ICD10: A09, K59.1]
Esophageal cancer [ICD9: 150; ICD10: C15]
Heart transplant rejection [ICD9: 996; ICD10: T86]
Intermittent claudication [ICD9: 440.21; ICD10: I73.9]
Inflammatory bowel disease [ICD9: 555, 556; ICD10: K50, K51]
Multiple myeloma [ICD9: 203; ICD10: C90]
Multiple myeloma; Anaemia [ICD9:203, 280-285, 585.9585.1-585.5403; ICD10: C90, D50-D64, N18]
Motor neurone disease; Amyotropic lateral sclerosis [ICD9: 335.2; ICD10: G12.2]
Neuropathic pain [ICD9: 356.0, 356.8; ICD10: G64, G90.0]
Ocular disease [ICD10: H00-H59]
Osteoarthritis [ICD9: 715; ICD10: M15-M19, M47]
Psoriasis [ICD9: 696; ICD10: L40]
Pemphigus vulgaris; Vasculitis; Wegener's granulomatosis [ICD10: C91-C95, J45, J84.1, L80, M081, M45, M35.0, M40-M54, T86.0]
Pneumonia [ICD10: J12-J18]
Psoriatic disorder [ICD9: 696; ICD10: L40]
Rheumatoid arthritis [ICD9: 710-719, 714; ICD10: M05-M06]
Rheumatoid arthritis; Dermatomyositis; Polymyositis; Juvenile rheumatoid arthritis; Graft-versus-host disease; Esophagitis [ICD10: K20, L40, M05-M06, M08.0, T86.0]
Rheumatoid arthritis; Psoriasis [ICD9: 696, 710-719, 714; ICD10: L40, M00-M25, M05-M06]
Rheumatold arthritis; Psoriatic arthritis; Ankylosing spondylitis [ICD9: 696.0, 710-719, 714, 720.0; ICD10: L40.5, M00-M25, M05-M06, M07, M08.1, M45]
Sciatica [ICD10: M54.3-M54.4]
Sepsis [ICD9: 995.91; ICD10: A40, A41]
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48]
Unspecified [ICD code not available]
Function
The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.
BioChemical Class
Cytokine: tumor necrosis factor
Target Validation
T20178
UniProt ID
P01375
Sequence
MSTESMIRDVELAEEALPKKTGGPQGSRRCLFLSLFSFLIVAGATTLFCLLHFGVIGPQR
EEFPRDLSLISPLAQAVRSSSRTPSDKPVAHVVANPQAEGQLQWLNRRANALLANGVELR
DNQLVVPSEGLYLIYSQVLFKGQGCPSTHVLLTHTISRIAVSYQTKVNLLSAIKSPCQRE
TPEGAEAKPWYEPIYLGGVFQLEKGDRLSAEINRPDYLDFAESGQVYFGIIAL
Drugs and Mode of Action
Drug(s) Adalimumab Drug Info Approved Rheumatoid arthritis [468081], [536711]
Certolizumab Drug Info Approved Rheumatoid arthritis [536651]
Certolizumab pegol Drug Info Approved Unspecified [551871]
Enbrel Drug Info Approved Active rheumatoid arthritis [1560300]
Etanercept Drug Info Approved Active rheumatoid arthritis [556264]
Golimumab Drug Info Approved Rheumatold arthritis; Psoriatic arthritis; Ankylosing spondylitis [530676], [530677], [541856]
Infliximab Drug Info Approved Crohn's disease; Ulcerative colitis; Rheumatoid arthritis; Ankylosing spondylitis; Psoriatic arthritis; Plaque psoriasis [468124], [536688], [889446]
Lenalidomide Drug Info Approved Multiple myeloma; Anaemia [537114], [542355], [551186], [551871]
Pentoxifylline Drug Info Approved Intermittent claudication [536772], [542101]
Thalidomide Drug Info Approved Multiple myeloma [536775], [542350]
ABP 501 Drug Info Phase 3 Rheumatoid arthritis [549501]
Etanercept Drug Info Phase 3 Sciatica [526617], [541869]
Golnerminogene pradenovac Drug Info Phase 3 Esophageal cancer [521542]
Infliximab Drug Info Phase 3 Asthma [468124], [536711]
Golimumab Drug Info Phase 2/3 Inflammatory bowel disease [530677], [541856]
ABT-122 Drug Info Phase 2 Rheumatoid arthritis [525076], [889413]
AN0128 Drug Info Phase 2 Atopic dermatitis; Psoriatic disorder [549847]
AP-301-IH Drug Info Phase 2 Pneumonia [524690]
DLX-105 Drug Info Phase 2 Osteoarthritis [523949]
ESBA-105 Drug Info Phase 2 Ocular disease [522546]
Etanercept Drug Info Phase 2 Pemphigus vulgaris; Vasculitis; Wegener's granulomatosis [889316], [889317], [889318], [889319], [889323], [889324], [889328], [889329], [889330], [889331], [889332], [889333], [889334], [889346], [889362], [889363], [889384], [889419]
Infliximab Drug Info Phase 2 Rheumatoid arthritis; Dermatomyositis; Polymyositis; Juvenile rheumatoid arthritis; Graft-versus-host disease; Esophagitis [889320], [889321], [889322], [889325], [889335], [889336], [889337], [889342], [889347], [889355]
IP-751 Drug Info Phase 2 Neuropathic pain [536374]
Pegsunercept Drug Info Phase 2 Rheumatoid arthritis [522132]
RDP58 Drug Info Phase 2 Diarrhea [535681]
TNF alpha kinoid Drug Info Phase 2 Autoimmune diabetes [524387]
COVA322 Drug Info Phase 1/2a Psoriasis [889403]
ART621 Drug Info Phase 1/2 Rheumatoid arthritis; Psoriasis [537117]
CYT-609 Drug Info Phase 1 Solid tumours [548408]
PF-05230905 Drug Info Phase 1 Rheumatoid arthritis [523333]
PF-06410293 Drug Info Phase 1 Rheumatoid arthritis [525336]
PF-06438179 Drug Info Phase 1 Rheumatoid arthritis [524274]
PMI-005 Drug Info Phase 1 Osteoarthritis [522849]
ABX-0401 Drug Info Preclinical Inflammatory bowel disease [547909]
Celastrol Drug Info Preclinical Motor neurone disease; Amyotropic lateral sclerosis [536447]
Genz29155 Drug Info Preclinical Heart transplant rejection [537129]
CDP571 Drug Info Discontinued in Phase 3 Crohn's disease [545606]
Segard Drug Info Discontinued in Phase 3 Sepsis [545307]
Camobucol Drug Info Discontinued in Phase 2 Rheumatoid arthritis [547347]
CRx-191 Drug Info Discontinued in Phase 2 Psoriatic disorder [548453]
CytoFab Drug Info Discontinued in Phase 2 Sepsis [546117]
AME-527 Drug Info Discontinued in Phase 1/2 Rheumatoid arthritis [547779]
CYT-007-TNFQb Drug Info Discontinued in Phase 1/2 Allergic rhinitis [548071]
ALS-00T2-0501 Drug Info Discontinued in Phase 1 Psoriasis [548268]
FR-133605 Drug Info Terminated Arthritis [534263]
MDL-201112 Drug Info Terminated Colitis [546299]
TNFQb therapeutic vaccines Drug Info Terminated Crohn's disease [549297]
Modulator ABT-122 Drug Info
ALS-00T2-0501 Drug Info [1572591]
CDP571 Drug Info
Certolizumab pegol Drug Info [533160]
COVA322 Drug Info [889442]
CYT-609 Drug Info [544154]
DOM-0215 Drug Info [1572605]
Enbrel Drug Info
Etanercept Drug Info [889443]
FR-133605 Drug Info [534263]
Golnerminogene pradenovac Drug Info [527709]
Inhibitor ABX-0401 Drug Info [550134]
AN0128 Drug Info [536282], [536599], [551129]
AP-301-IH Drug Info [532192]
ART621 Drug Info [537117]
BAICALEIN Drug Info [531164]
Camobucol Drug Info [527425]
Certolizumab Drug Info [536651]
CRx-191 Drug Info [551126]
CYT-007-TNFQb Drug Info [544452]
Genz29155 Drug Info [537129]
IK-682 Drug Info [526446]
IP-751 Drug Info [536374]
Isopropyl Alcohol Drug Info [551374]
Lenalidomide Drug Info [536378], [537229]
MDL-201112 Drug Info [533875]
Pegsunercept Drug Info [529415]
PF-05230905 Drug Info [549168]
PF-06438179 Drug Info [532736]
PKF-241-466 Drug Info [526335]
PKF-242-484 Drug Info [526335]
PMI-005 Drug Info [551903]
RDP58 Drug Info [535681]
Thalidomide Drug Info [536993]
Y-39041 Drug Info [535084]
Suppressor Celastrol Drug Info [536447]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway MAPK signaling pathway
Cytokine-cytokine receptor interaction
NF-kappa B signaling pathway
Sphingolipid signaling pathway
mTOR signaling pathway
Apoptosis
TGF-beta signaling pathway
Osteoclast differentiation
Antigen processing and presentation
Toll-like receptor signaling pathway
NOD-like receptor signaling pathway
RIG-I-like receptor signaling pathway
Hematopoietic cell lineage
Natural killer cell mediated cytotoxicity
T cell receptor signaling pathway
Fc epsilon RI signaling pathway
TNF signaling pathway
Adipocytokine signaling pathway
Type II diabetes mellitus
Non-alcoholic fatty liver disease (NAFLD)
Type I diabetes mellitus
Alzheimer&#039
s disease
Amyotrophic lateral sclerosis (ALS)
Pertussis
Legionellosis
Leishmaniasis
Chagas disease (American trypanosomiasis)
African trypanosomiasis
Malaria
Toxoplasmosis
Amoebiasis
Tuberculosis
Hepatitis C
Hepatitis B
Influenza A
HTLV-I infection
Herpes simplex infection
Proteoglycans in cancer
Asthma
Inflammatory bowel disease (IBD)
Systemic lupus erythematosus
Rheumatoid arthritis
Allograft rejection
Graft-versus-host disease
Hypertrophic cardiomyopathy (HCM)
Dilated cardiomyopathy
NetPath Pathway TCR Signaling Pathway
IL2 Signaling Pathway
IL3 Signaling Pathway
IL4 Signaling Pathway
Leptin Signaling Pathway
RANKL Signaling Pathway
IL1 Signaling Pathway
PANTHER Pathway Apoptosis signaling pathway
Wnt signaling pathway
Pathway Interaction Database IL27-mediated signaling events
Canonical NF-kappaB pathway
Calcineurin-regulated NFAT-dependent transcription in lymphocytes
Angiopoietin receptor Tie2-mediated signaling
Signaling events mediated by HDAC Class I
TNF receptor signaling pathway
Ceramide signaling pathway
amb2 Integrin signaling
RXR and RAR heterodimerization with other nuclear receptor
IL23-mediated signaling events
Negative effector of Fas and TNF-alpha
Caspase Cascade in Apoptosis
Cellular roles of Anthrax toxin
Downstream signaling in na&amp
#xef
ve CD8+ T cells
PathWhiz Pathway Fc Epsilon Receptor I Signaling in Mast Cells
Reactome Transcriptional regulation of white adipocyte differentiation
TNFR1-induced proapoptotic signaling
Regulation of TNFR1 signaling
TNFR1-induced NFkappaB signaling pathway
TNFR1-mediated ceramide production
TNFR2 non-canonical NF-kB pathway
TNF signaling
WikiPathways Toll-like receptor signaling pathway
Monoamine Transport
SIDS Susceptibility Pathways
TGF Beta Signaling Pathway
Cytokines and Inflammatory Response
MAPK Signaling Pathway
EV release from cardiac cells and their functional effects
FAS pathway and Stress induction of HSP regulation
Apoptosis-related network due to altered Notch3 in ovarian cancer
Cardiac Hypertrophic Response
Transcriptional Regulation of White Adipocyte Differentiation
Aryl Hydrocarbon Receptor
Apoptosis
Nanoparticle triggered regulated necrosis
Amyotrophic lateral sclerosis (ALS)
Adipogenesis
Allograft Rejection
TNF alpha Signaling Pathway
TWEAK Signaling Pathway
Extrinsic Pathway for Apoptosis
Folate Metabolism
MicroRNAs in cardiomyocyte hypertrophy
Vitamin B12 Metabolism
Selenium Micronutrient Network
Regulation of toll-like receptor signaling pathway
Matrix Metalloproteinases
References
Ref 468081(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4860).
Ref 468124(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5004).
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Ref 525076ClinicalTrials.gov (NCT02349451) A Phase 2 Study to Investigate the Safety, Tolerability and Efficacy of ABT-122 in Subjects With Active Psoriatic Arthritis Who Have an Inadequate Response to Methotrexate. U.S. National Institutes of Health.
Ref 525336ClinicalTrials.gov (NCT02572245) A Study of PF-06410293 Following Subcutaneous Administration Using A Prefilled Syringe Or A Prefilled Pen In Healthy Adult Subjects.
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Ref 530676Golimumab: a tumor necrosis factor alpha inhibitor for the treatment of rheumatoid arthritis. Ann Pharmacother. 2010 Jan;44(1):135-44.
Ref 530677Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
Ref 534263Effect of FR133605, a novel cytokine suppressive agent, on bone and cartilage destruction in adjuvant arthritic rats. J Rheumatol. 1996 Oct;23(10):1778-83.
Ref 535681RDP58, a locally active TNF inhibitor, is effective in the dextran sulphate mouse model of chronic colitis. Inflamm Res. 2002 Nov;51(11):522-31.
Ref 536374Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.
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Ref 536688Drug 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.
Ref 536711Molecular targets of rheumatoid arthritis. Inflamm Allergy Drug Targets. 2008 Mar;7(1):53-66.
Ref 536772New drugs in development for the treatment of endometriosis. Expert Opin Investig Drugs. 2008 Aug;17(8):1187-202.
Ref 536775Thalidomide in multiple myeloma--clinical trials and aspects of drug metabolism and toxicity. Expert Opin Drug Metab Toxicol. 2008 Jul;4(7):973-85.
Ref 537114Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
Ref 537117Emerging drugs for psoriasis. Expert Opin Emerg Drugs. 2009 Mar;14(1):145-63.
Ref 537129New developments in immunosuppressive therapy for heart transplantation. Expert Opin Emerg Drugs. 2009 Mar;14(1):1-21.
Ref 541856(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6776).
Ref 541869(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6789).
Ref 542101(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7095).
Ref 542350(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7327).
Ref 542355(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7331).
Ref 545307Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002771)
Ref 545606Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003884)
Ref 546117Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006437)
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Ref 889318ClinicalTrials.gov (NCT00005007) Etanercept for Wegener's Granulomatosis
Ref 889319ClinicalTrials.gov (NCT00006070) Etanercept (Enbrel) to Treat Pain and Swelling After Third Molar Extraction
Ref 889320ClinicalTrials.gov (NCT00006292) Infliximab for the Treatment of Early Rheumatoid Arthritis
Ref 889321ClinicalTrials.gov (NCT00029042) Infliximab to Treat Children With Juvenile Rheumatoid Arthritis
Ref 889322ClinicalTrials.gov (NCT00033891) Infliximab (Remicade ) to Treat Dermatomyositis and Polymyositis
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Ref 889324ClinicalTrials.gov (NCT00063869) Study Evaluating the Safety and Efficacy of Etanercept in Patients With Idiopathic Pulmonary Fibrosis
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Ref 889330ClinicalTrials.gov (NCT00135720) Study of Etanercept (Enbrel) in the Treatment of Pemphigus Vulgaris
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Ref 889332ClinicalTrials.gov (NCT00141726) Study of Enbrel (Etanercept) for the Treatment Sub-Acute Pulmonary Dysfunction After Allogeneic Stem Cell Transplant
Ref 889333ClinicalTrials.gov (NCT00141739) Study of Etanercept for the Prevention of Complications Resulting From Hematopoietic Stem Cell Transplantation (HSCT)
Ref 889334ClinicalTrials.gov (NCT00141791) Study Evaluating Etanercept in Moderate to Severe Asthma
Ref 889335ClinicalTrials.gov (NCT00201799) Infliximab for the Prevention of Graft-versus-Host Disease Following Allogenic Hematopoietic Stem Cell Transplantation
Ref 889336ClinicalTrials.gov (NCT00230529) A Safety and Efficacy Study of Infliximab (Remicade) in Patients With Plaque Type Psoriasis
Ref 889337ClinicalTrials.gov (NCT00244192) Effects of Infliximab (Remicade) on Fat Free Mass in Patients With Moderate to Severe COPD Suffering From Cachexia
Ref 889342ClinicalTrials.gov (NCT00443222) Treatment With TNF Blockade, Infliximab, in Patients With Myositis
Ref 889346ClinicalTrials.gov (NCT00509600) Etanercept (Enbrel) for Juvenile Myelomonocytic Leukemia
Ref 889347ClinicalTrials.gov (NCT00523354) Off Label Use of Infliximab in Adult Patients With Severe Eosinophilic Esophagitis
Ref 889355ClinicalTrials.gov (NCT00823641) The HAM Infliximab Study
Ref 889362ClinicalTrials.gov (NCT01289730) Etanercept (Enbrel) in Undifferentiated Spondyloarthritis
Ref 889363ClinicalTrials.gov (NCT01289743) Etanercept (Enbrel) in Ankylosing Spondylitis
Ref 889384ClinicalTrials.gov (NCT01730495) Tumor Necrosis Factor-alpha Inhibition Using Etanercept in Chronic Fatigue Syndrome
Ref 889403ClinicalTrials.gov (NCT02243787) Safety and Tolerability Study of COVA322 in Patients With Stable Chronic Moderate-to-severe Plaque Psoriasis
Ref 889413ClinicalTrials.gov (NCT02433340) Phase 2, Multicenter, Open-Label Extension (OLE) Study With ABT-122 in Rheumatoid Arthritis Subjects Who Have Completed the Preceding M12-963 Study
Ref 889419ClinicalTrials.gov (NCT02656082) Targeted Therapy Using Intradermal Injection of Etanercept for Remission Induction in Discoid Lupus Erythematosus
Ref 889446Drugs@FDA (Edaravone)
Ref 1560300Oral pentoxifylline inhibits release of tumor necrosis factor-alpha from human peripheral blood monocytes : a potential treatment for aseptic loosening of total joint components.
Ref
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Ref 527425AGIX-4207 [2-[4-[[1-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]thio]-1-methylethyl]thio]-2,6-bis(1,1-dimethylethyl)phenoxy]acetic acid], a novel antioxidant and anti-inflammatory compound: cellularand biochemical characterization of antioxidant activity and inhibition of redox-sensitive inflammatory gene expression. J Pharmacol Exp Ther. 2005 May;313(2):492-501. Epub 2005 Feb 8.
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Ref 529663Pharmacokinetics and posterior segment biodistribution of ESBA105, an anti-TNF-alpha single-chain antibody, upon topical administration to the rabbit eye. Invest Ophthalmol Vis Sci. 2009 Feb;50(2):771-8.
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Ref 531164Bioorg 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.
Ref 532192AP301, a synthetic peptide mimicking the lectin-like domain of TNF, enhances amiloride-sensitive Na(+) current in primary dog, pig and rat alveolar type II cells. Pulm Pharmacol Ther. 2013 Jun;26(3):356-63.
Ref 532736Biosimilars in the therapy of inflammatory bowel diseases. Eur J Gastroenterol Hepatol. 2014 Jun;26(6):581-7.
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