Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCQL07Z)

• DOT Name: Interleukin-6 receptor subunit alpha (IL6R)
• Synonyms: IL-6 receptor subunit alpha; IL-6R subunit alpha; IL-6R-alpha; IL-6RA; IL-6R 1; Membrane glycoprotein 80; gp80; CD antigen CD126
• Gene Name: IL6R
• Related Disease:
  Abdominal aortic aneurysm
  Alzheimer disease
  Castleman's disease
  Anterior uveitis
  Atrial fibrillation
  Breast cancer
  Breast carcinoma
  Cardiac failure
  Clear cell renal carcinoma
  Congestive heart failure
  Coronary atherosclerosis
  Crohn disease
  Depression
  Epithelial ovarian cancer
  Hepatocellular carcinoma
  Hyper-IgE recurrent infection syndrome 5, autosomal recessive
  Juvenile idiopathic arthritis
  Lung cancer
  Lung carcinoma
  Myocardial infarction
  Neoplasm
  Non-small-cell lung cancer
  Obesity
  Osteoporosis
  Papillary renal cell carcinoma
  Plasma cell myeloma
  Renal cell carcinoma
  Sciatic neuropathy
  Ulcerative colitis
  Advanced cancer
  Schizophrenia
  Ankylosing spondylitis
  Asthma
  Atopic dermatitis
  Coronary heart disease
  Gastric cancer
  Gastric neoplasm
  Hereditary diffuse gastric adenocarcinoma
  Psoriasis
  Sclerosing cholangitis
• UniProt ID: IL6RA_HUMAN
• PDB ID: 1N26; 1P9M; 2ARW; 5FUC; 7DC8; 8D82
• Pfam ID: PF00047 ; PF09240
• Sequence:
  MLAVGCALLAALLAAPGAALAPRRCPAQEVARGVLTSLPGDSVTLTCPGVEPEDNATVHW
  VLRKPAAGSHPSRWAGMGRRLLLRSVQLHDSGNYSCYRAGRPAGTVHLLVDVPPEEPQLS
  CFRKSPLSNVVCEWGPRSTPSLTTKAVLLVRKFQNSPAEDFQEPCQYSQESQKFSCQLAV
  PEGDSSFYIVSMCVASSVGSKFSKTQTFQGCGILQPDPPANITVTAVARNPRWLSVTWQD
  PHSWNSSFYRLRFELRYRAERSKTFTTWMVKDLQHHCVIHDAWSGLRHVVQLRAQEEFGQ
  GEWSEWSPEAMGTPWTESRSPPAENEVSTPMQALTTNKDDDNILFRDSANATSLPVQDSS
  SVPLPTFLVAGGSLAFGTLLCIAIVLRFKKTWKLRALKEGKTSMHPPYSLGQLVPERPRP
  TPVLVPLISPPVSPSSLGSDNTSSHNRPDARDPRSPYDISNTDYFFPR
• Function: Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal. Signal activation necessitate an association with IL6ST. Activation leads to the regulation of the immune response, acute-phase reactions and hematopoiesis. The interaction with membrane-bound IL6R and IL6ST stimulates 'classic signaling', the restricted expression of the IL6R limits classic IL6 signaling to only a few tissues such as the liver and some cells of the immune system. Whereas the binding of IL6 and soluble IL6R to IL6ST stimulates 'trans-signaling'. Alternatively, 'cluster signaling' occurs when membrane-bound IL6:IL6R complexes on transmitter cells activate IL6ST receptors on neighboring receiver cells (Probable); [Isoform 1]: Signaling via the membrane-bound IL6R is mostly regenerative and anti-inflammatory (Probable). Drives naive CD4(+) T cells to the Th17 lineage, through 'cluster signaling' by dendritic cells; [Isoform 2]: Soluble form of IL6 receptor (sIL6R) that acts as an agonist of IL6 activity. The IL6:sIL6R complex (hyper-IL6) binds to IL6ST/gp130 on cell surfaces and induces signaling also on cells that do not express membrane-bound IL6R in a process called IL6 'trans-signaling'. sIL6R is causative for the pro-inflammatory properties of IL6 and an important player in the development of chronic inflammatory diseases. In complex with IL6, is required for induction of VEGF production. Plays a protective role during liver injury, being required for maintenance of tissue regeneration. 'Trans-signaling' in central nervous system regulates energy and glucose homeostasis; [Soluble interleukin-6 receptor subunit alpha]: Soluble form of IL6 receptor (sIL6R) that acts as an agonist of IL6 activity. The IL6:sIL6R complex (hyper-IL6) binds to IL6ST/gp130 on cell surfaces and induces signaling also on cells that do not express membrane-bound IL6R in a process called IL6 'trans-signaling'. sIL6R is causative for the pro-inflammatory properties of IL6 and an important player in the development of chronic inflammatory diseases. In complex with IL6, is required for induction of VEGF production. Plays a protective role during liver injury, being required for maintenance of tissue regeneration. 'Trans-signaling' in central nervous system regulates energy and glucose homeostasis.
• Tissue Specificity: .Expressed in peripheral blood mononuclear cells and weakly found in urine and serum. 1%-20% of the total sIL6R in plasma is generated by alternative splicing .
• KEGG Pathway:
  EGFR tyrosine ki.se inhibitor resistance (hsa01521)
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  HIF-1 sig.ling pathway (hsa04066)
  PI3K-Akt sig.ling pathway (hsa04151)
  JAK-STAT sig.ling pathway (hsa04630)
  Hematopoietic cell lineage (hsa04640)
  Th17 cell differentiation (hsa04659)
  Non-alcoholic fatty liver disease (hsa04932)
  Human cytomegalovirus infection (hsa05163)
  Coro.virus disease - COVID-19 (hsa05171)
  Pathways in cancer (hsa05200)
• Reactome Pathway:
  MAPK3 (ERK1) activation (R-HSA-110056)
  MAPK1 (ERK2) activation (R-HSA-112411)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  Transcriptional regulation of granulopoiesis (R-HSA-9616222)
  Potential therapeutics for SARS (R-HSA-9679191)
  Interleukin-6 signaling (R-HSA-1059683)

Molecular Interaction Atlas (MIA) of This DOT

40 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Abdominal aortic aneurysm	DISD06OF	Definitive	Genetic Variation	[1]
Alzheimer disease	DISF8S70	Definitive	Genetic Variation	[2]
Castleman's disease	DISVC11M	Definitive	Biomarker	[3]
Anterior uveitis	DISQ7EAD	Strong	Genetic Variation	[4]
Atrial fibrillation	DIS15W6U	Strong	Altered Expression	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Cardiac failure	DISDC067	Strong	Biomarker	[7]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[8]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[7]
Coronary atherosclerosis	DISKNDYU	Strong	Genetic Variation	[9]
Crohn disease	DIS2C5Q8	Strong	Genetic Variation	[10]
Depression	DIS3XJ69	Strong	Genetic Variation	[11]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[12]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[13]
Hyper-IgE recurrent infection syndrome 5, autosomal recessive	DISBM7C5	Strong	Autosomal recessive	[14]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[15]
Lung cancer	DISCM4YA	Strong	Biomarker	[16]
Lung carcinoma	DISTR26C	Strong	Biomarker	[16]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[17]
Neoplasm	DISZKGEW	Strong	Altered Expression	[18]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[19]
Obesity	DIS47Y1K	Strong	Altered Expression	[13]
Osteoporosis	DISF2JE0	Strong	Biomarker	[20]
Papillary renal cell carcinoma	DIS25HBV	Strong	Biomarker	[8]
Plasma cell myeloma	DIS0DFZ0	Strong	Altered Expression	[21]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[8]
Sciatic neuropathy	DISMGDKX	Strong	Biomarker	[22]
Ulcerative colitis	DIS8K27O	Strong	Genetic Variation	[10]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[23]
Schizophrenia	DISSRV2N	moderate	Genetic Variation	[24]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[25]
Asthma	DISW9QNS	Limited	Biomarker	[26]
Atopic dermatitis	DISTCP41	Limited	Genetic Variation	[27]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[28]
Gastric cancer	DISXGOUK	Limited	Biomarker	[29]
Gastric neoplasm	DISOKN4Y	Limited	Biomarker	[29]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Limited	Biomarker	[29]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[25]
Sclerosing cholangitis	DIS7GZNB	Limited	Genetic Variation	[25]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitomycin	DMH0ZJE	Approved	Interleukin-6 receptor subunit alpha (IL6R) decreases the response to substance of Mitomycin.	[8]

44 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[30]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[31]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[32]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[33]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[34]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[35]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[36]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[37]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[38]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[29]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[40]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[41]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[42]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Interleukin-6 receptor subunit alpha (IL6R).	[43]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol increases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[44]
Azacitidine	DMTA5OE	Approved	Azacitidine affects the expression of Interleukin-6 receptor subunit alpha (IL6R).	[45]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[46]
Daunorubicin	DMQUSBT	Approved	Daunorubicin decreases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[47]
Acocantherin	DM7JT24	Approved	Acocantherin increases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[48]
Mebendazole	DMO14SG	Approved	Mebendazole increases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[47]
Epirubicin	DMPDW6T	Approved	Epirubicin increases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[49]
Emetine	DMCT2YF	Approved	Emetine decreases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[47]
Digoxin	DMQCTIH	Approved	Digoxin decreases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[47]
Albendazole	DMYZ57N	Approved	Albendazole increases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[47]
Tecfidera	DM2OVDT	Approved	Tecfidera decreases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[50]
Oxytetracycline	DMOVH1M	Approved	Oxytetracycline decreases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[47]
Meclocycline	DMSFQ8I	Approved	Meclocycline decreases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[47]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[51]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[52]
Camptothecin	DM6CHNJ	Phase 3	Camptothecin decreases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[47]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[53]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[54]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[55]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 decreases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[56]
Puromycin	DMDKLB5	Preclinical	Puromycin decreases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[47]
Cephaeline	DM1ZFCS	Preclinical	Cephaeline decreases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[47]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[57]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[30]
Milchsaure	DM462BT	Investigative	Milchsaure affects the expression of Interleukin-6 receptor subunit alpha (IL6R).	[58]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[59]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[60]
PALMATINE	DMJCOKV	Investigative	PALMATINE decreases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[47]
Propidium	DMZ1FRS	Investigative	Propidium decreases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[47]
Digitoxigenin	DM5AOFW	Investigative	Digitoxigenin decreases the expression of Interleukin-6 receptor subunit alpha (IL6R).	[47]

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