Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT0E5SK)

• DTT Name: Interleukin 6 receptor (IL6R)
• Synonyms: Membrane glycoprotein; Interleukin-6 receptor; IL-6R; IL-6 receptor
• Gene Name: IL6R
• DTT Type: Successful target; [1]
• BioChemical Class: Cytokine receptor
• UniProt ID: IL6RA_HUMAN ; IL6RB_HUMAN
• TTD ID: T93440
• Sequence:
  MLAVGCALLAALLAAPGAALAPRRCPAQEVARGVLTSLPGDSVTLTCPGVEPEDNATVHW
  VLRKPAAGSHPSRWAGMGRRLLLRSVQLHDSGNYSCYRAGRPAGTVHLLVDVPPEEPQLS
  CFRKSPLSNVVCEWGPRSTPSLTTKAVLLVRKFQNSPAEDFQEPCQYSQESQKFSCQLAV
  PEGDSSFYIVSMCVASSVGSKFSKTQTFQGCGILQPDPPANITVTAVARNPRWLSVTWQD
  PHSWNSSFYRLRFELRYRAERSKTFTTWMVKDLQHHCVIHDAWSGLRHVVQLRAQEEFGQ
  GEWSEWSPEAMGTPWTESRSPPAENEVSTPMQALTTNKDDDNILFRDSANATSLPVQDSS
  SVPLPTFLVAGGSLAFGTLLCIAIVLRFKKTWKLRALKEGKTSMHPPYSLGQLVPERPRP
  TPVLVPLISPPVSPSSLGSDNTSSHNRPDARDPRSPYDISNTDYFFPR
• Function: Low concentration of a soluble form of IL6 receptor acts as an agonist of IL6 activity.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  HIF-1 signaling pathway (hsa04066)
  PI3K-Akt signaling pathway (hsa04151)
  Jak-STAT signaling pathway (hsa04630)
  Hematopoietic cell lineage (hsa04640)
  Non-alcoholic fatty liver disease (NAFLD) (hsa04932)
• Reactome Pathway:
  MAPK1 (ERK2) activation (R-HSA-112411)
  MAPK3 (ERK1) activation (R-HSA-110056)

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sarilumab	DMOGNXY	Rheumatoid arthritis	FA20	Approved	[2]
Tocilizumab	DM7J6OR	Giant cell arteritis	4A44.2	Approved	[1]

5 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SA-237	DM7F2VG	Encephalopathy	8E47	Phase 3	[3]
SAR153191	DMXAO4J	Ankylosing spondylitis	FA92.0	Phase 3	[4]
Sirukumab	DMK8AQP	Cutaneous lupus erythematosus	EB5Z	Phase 3	[5]
ALX-0061	DMO1VHC	Autoimmune diabetes	5A10	Phase 2	[6]
Vobarilizumab	DM9KNJT	Rheumatoid arthritis	FA20	Phase 2	[7]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SBP-002	DM9F7R0	Melanoma	2C30	Terminated	[2]

4 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Alpha-D-Mannose	DMF5DLW	Discovery agent	N.A.	Investigative	[8]
FM-101	DMXK6EI	Multiple myeloma	2A83	Investigative	[5]
NI-1201	DM680XO	Autoimmune diabetes	5A10	Investigative	[5]
Sant7	DM9CV4P	Multiple myeloma	2A83	Investigative	[9]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Melanoma	2C82	Skin	1.13E-04	1.32	1.28
Type 2 diabetes	5A11	Liver tissue	5.77E-01	-0.24	-0.47
Rheumatoid arthritis	FA20	Synovial tissue	2.25E-01	0.38	0.36
Multiple myeloma	2C82	Bone marrow	4.80E-03	1.08	1.67

References

• [1] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [3] IBC's 23rd Annual Antibody Engineering, 10th Annual Antibody Therapeutics International Conferences and the 2012 Annual Meeting of The Antibody Society: December 3-6, 2012, San Diego, CA. MAbs. 2013 March 1; 5(2): 178-201.
• [4] Pharma & Vaccines. Product Development Pipeline. April 29 2009.
• [5] URL: 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. (Target id: 2310).
• [6] The preclinical pharmacology of the high affinity anti-IL-6R Nanobody ALX-0061 supports its clinical development in rheumatoid arthritis. Arthritis Res Ther. 2015 May 20;17:135.
• [7] Clinical pipeline report, company report or official report of Ablynx.
• [8] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [9] Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.