Target Information

Target General Infomation
Target ID
T32578
Former ID
TTDC00080
Target Name
Interleukin-6
Gene Name
IL6
Synonyms
B-cell stimulatory factor 2; BSF-2; CDF; CTL differentiation factor; Hybridoma growth factor; IL-6; Interferon beta-2; IL6
Target Type
Successful
Disease Anemia [ICD9: 280-285; ICD10: D50-D64]
Crohn's disease [ICD9: 555; ICD10: K50]
Hematological malignancies [ICD9: 200-209; ICD10: C81-C86]
Opioid-related disorders; Diabetic neuropathy [ICD9: 250, 250.6, 292, 304.0, 305.50, 356.0, 356.8; ICD10: E08-E13, E10.4, E11.4, E13.4, F11, G64, G90.0]
Psoriatic arthritis; Rheumatoid arthritis [ICD9: 696.0, 710-719, 714; ICD10: L40.5, M00-M25, M05-M06, M07]
Rheumatoid arthritis [ICD9: 710-719, 714; ICD10: M05-M06]
Function
Cytokine with a wide variety of biologicalfunctions. It is a potent inducer of the acute phase response. Plays an essential role in the final differentiation of B-cells into Ig- secreting cells Involved in lymphocyte and monocyte differentiation. Acts on B-cells, T-cells, hepatocytes, hematopoietic progenitor cells and cells of the CNS. Required for the generation of T(H)17 cells. Also acts as a myokine. It is discharged into the bloodstream after muscle contraction and acts to increase the breakdown of fats and to improve insulin resistance. It induces myeloma and plasmacytoma growth and induces nerve cells differentiation.
BioChemical Class
Cytokine: interleukin
Target Validation
T32578
UniProt ID
P05231
Sequence
MNSFSTSAFGPVAFSLGLLLVLPAAFPAPVPPGEDSKDVAAPHRQPLTSSERIDKQIRYI
LDGISALRKETCNKSNMCESSKEALAENNLNLPKMAEKDGCFQSGFNEETCLVKIITGLL
EFEVYLEYLQNRFESSEEQARAVQMSTKVLIQFLQKKAKNLDAITTPDPTTNASLLTKLQ
AQNQWLQDMTTHLILRSFKEFLQSSLRALRQM
Drugs and Mode of Action
Drug(s) Siltuximab Drug Info Approved Anemia [533123], [542417], [551871]
ALD-518 Drug Info Phase 2 Psoriatic arthritis; Rheumatoid arthritis [1572591]
CDP-6038 Drug Info Phase 2 Rheumatoid arthritis [1572591]
Ibudilast Drug Info Phase 2 Opioid-related disorders; Diabetic neuropathy [536374], [542420]
Olokizumab Drug Info Phase 2 Rheumatoid arthritis [523674]
YSIL6 Drug Info Phase 2 Crohn's disease [547912]
C326 Drug Info Phase 1 Crohn's disease [521856]
MEDI5117 Drug Info Phase 1 Rheumatoid arthritis [523841]
OP-R003 Drug Info Phase 1 Hematological malignancies [549241]
Modulator ALD-518 Drug Info [1572591]
CDP-6038 Drug Info [1572591]
MEDI5117 Drug Info [531539]
Olokizumab Drug Info [544437]
OP-R003 Drug Info
Inhibitor C326 Drug Info [537252]
Ibudilast Drug Info [536374]
YSIL6 Drug Info [547913]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Cytokine-cytokine receptor interaction
HIF-1 signaling pathway
FoxO signaling pathway
PI3K-Akt signaling pathway
Toll-like receptor signaling pathway
NOD-like receptor signaling pathway
Cytosolic DNA-sensing pathway
Jak-STAT signaling pathway
Hematopoietic cell lineage
TNF signaling pathway
Intestinal immune network for IgA production
Non-alcoholic fatty liver disease (NAFLD)
Prion diseases
Salmonella infection
Pertussis
Legionellosis
Chagas disease (American trypanosomiasis)
African trypanosomiasis
Malaria
Amoebiasis
Tuberculosis
Hepatitis B
Measles
Influenza A
HTLV-I infection
Herpes simplex infection
Pathways in cancer
Transcriptional misregulation in cancer
Inflammatory bowel disease (IBD)
Rheumatoid arthritis
Graft-versus-host disease
Hypertrophic cardiomyopathy (HCM)
NetPath Pathway IL1 Signaling Pathway
TWEAK Signaling Pathway
TCR Signaling Pathway
IL2 Signaling Pathway
IL4 Signaling Pathway
TGF_beta_Receptor Signaling Pathway
TNFalpha Signaling Pathway
Alpha6Beta4Integrin Signaling Pathway
TSLP Signaling Pathway
Leptin Signaling Pathway
RANKL Signaling Pathway
IL5 Signaling Pathway
PANTHER Pathway Interleukin signaling pathway
Pathway Interaction Database LPA receptor mediated events
IL27-mediated signaling events
Validated transcriptional targets of AP1 family members Fra1 and Fra2
SHP2 signaling
Glucocorticoid receptor regulatory network
amb2 Integrin signaling
ATF-2 transcription factor network
AP-1 transcription factor network
IL6-mediated signaling events
IL23-mediated signaling events
Reactome Interleukin-6 signaling
MAPK3 (ERK1) activation
MAPK1 (ERK2) activation
Senescence-Associated Secretory Phenotype (SASP)
WikiPathways Toll-like receptor signaling pathway
SIDS Susceptibility Pathways
TCR Signaling Pathway
Senescence and Autophagy in Cancer
Cytokines and Inflammatory Response
IL-6 signaling pathway
Myometrial Relaxation and Contraction Pathways
Hematopoietic Stem Cell Differentiation
Differentiation Pathway
Interleukin-6 signaling
Spinal Cord Injury
Adipogenesis
TNF alpha Signaling Pathway
TSLP Signaling Pathway
TWEAK Signaling Pathway
Folate Metabolism
Vitamin B12 Metabolism
Selenium Micronutrient Network
Regulation of toll-like receptor signaling pathway
References
Ref 521856ClinicalTrials.gov (NCT00353756) Phase 1 Study of Safety and Biological Effects of C326, an Inhibitor of IL-6, in Crohn's Disease. U.S. National Institutes of Health.
Ref 523674ClinicalTrials.gov (NCT01463059) Efficacy and Safety of Olokizumab With Rheumatoid Arthritis With Previously Failed to Anti-tumor Necrosis Factor (Anti-TNF) Therapy. U.S. National Institutes of Health.
Ref 523841ClinicalTrials.gov (NCT01559103) Study to Assess the Safety and Tolerability of MEDI5117 in Rheumatoid Arthritis Patients. U.S. National Institutes of Health.
Ref 5331232014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
Ref 536374Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.
Ref 542417(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: 7396).
Ref 542420(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: 7399).
Ref 547912Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020380)
Ref 549241Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800034097)
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 1572591Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
Ref
Ref 531539Whole-molecule antibody engineering: generation of a high-affinity anti-IL-6 antibody with extended pharmacokinetics. J Mol Biol. 2011 Aug 26;411(4):791-807.
Ref 5331232014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
Ref 536374Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.
Ref 537252The molecular basis of hepcidin-resistant hereditary hemochromatosis. Blood. 2009 Jul 9;114(2):437-43. Epub 2009 Apr 21.
Ref 544437Efficacy and safety of olokizumab in patients with rheumatoid arthritis with an inadequate response to TNF inhibitor therapy: outcomes of a randomised Phase IIb study. Ann Rheum Dis. 2014 September; 73(9): 1607-1615.
Ref 547913Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020380)
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 1572591Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.

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