Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1N9C70)

• DOT Name: Interleukin-6 receptor subunit beta (IL6ST)
• Synonyms: IL-6 receptor subunit beta; IL-6R subunit beta; IL-6R-beta; IL-6RB; CDw130; Interleukin-6 signal transducer; Membrane glycoprotein 130; gp130; Oncostatin-M receptor subunit alpha; CD antigen CD130
• Gene Name: IL6ST
• Related Disease:
  Melanoma
  Allergy
  Alzheimer disease
  Autoimmune disease
  Breast cancer
  Breast carcinoma
  Cardiac failure
  Colorectal carcinoma
  Colorectal neoplasm
  Gastric neoplasm
  Hyper-IgE recurrent infection syndrome 4, autosomal recessive
  Hyper-IgE recurrent infection syndrome 4A, autosomal dominant
  Liver cancer
  Lung cancer
  Lung carcinoma
  Myocardial infarction
  Myocardial ischemia
  Neoplasm
  Non-insulin dependent diabetes
  Osteoarthritis
  Ovarian cancer
  Ovarian neoplasm
  Pituitary tumor
  Plasma cell myeloma
  Pneumonia
  Pneumonitis
  Prostate cancer
  Prostate neoplasm
  Systemic sclerosis
  Urinary bladder cancer
  Urinary bladder neoplasm
  Arteriosclerosis
  Atherosclerosis
  Congestive heart failure
  Hepatocellular carcinoma
  Multiple sclerosis
  Adenocarcinoma
  Undifferentiated carcinoma
  Acute myelogenous leukaemia
  Carcinoma
  Colon cancer
  Colon carcinoma
  Crohn disease
  Non-small-cell lung cancer
  Obesity
  Pancreatic cancer
  Status epilepticus seizure
• UniProt ID: IL6RB_HUMAN
• PDB ID: 1BJ8; 1BQU; 1I1R; 1P9M; 1PVH; 3L5H; 3L5I; 3L5J; 7U7N; 8D6A; 8D74; 8D7R; 8D82; 8D85; 8DPS; 8DPT; 8DPU
• Pfam ID: PF00041 ; PF09240 ; PF06328
• Sequence:
  MLTLQTWLVQALFIFLTTESTGELLDPCGYISPESPVVQLHSNFTAVCVLKEKCMDYFHV
  NANYIVWKTNHFTIPKEQYTIINRTASSVTFTDIASLNIQLTCNILTFGQLEQNVYGITI
  ISGLPPEKPKNLSCIVNEGKKMRCEWDGGRETHLETNFTLKSEWATHKFADCKAKRDTPT
  SCTVDYSTVYFVNIEVWVEAENALGKVTSDHINFDPVYKVKPNPPHNLSVINSEELSSIL
  KLTWTNPSIKSVIILKYNIQYRTKDASTWSQIPPEDTASTRSSFTVQDLKPFTEYVFRIR
  CMKEDGKGYWSDWSEEASGITYEDRPSKAPSFWYKIDPSHTQGYRTVQLVWKTLPPFEAN
  GKILDYEVTLTRWKSHLQNYTVNATKLTVNLTNDRYLATLTVRNLVGKSDAAVLTIPACD
  FQATHPVMDLKAFPKDNMLWVEWTTPRESVKKYILEWCVLSDKAPCITDWQQEDGTVHRT
  YLRGNLAESKCYLITVTPVYADGPGSPESIKAYLKQAPPSKGPTVRTKKVGKNEAVLEWD
  QLPVDVQNGFIRNYTIFYRTIIGNETAVNVDSSHTEYTLSSLTSDTLYMVRMAAYTDEGG
  KDGPEFTFTTPKFAQGEIEAIVVPVCLAFLLTTLLGVLFCFNKRDLIKKHIWPNVPDPSK
  SHIAQWSPHTPPRHNFNSKDQMYSDGNFTDVSVVEIEANDKKPFPEDLKSLDLFKKEKIN
  TEGHSSGIGGSSCMSSSRPSISSSDENESSQNTSSTVQYSTVVHSGYRHQVPSVQVFSRS
  ESTQPLLDSEERPEDLQLVDHVDGGDGILPRQQYFKQNCSQHESSPDISHFERSKQVSSV
  NEEDFVRLKQQISDHISQSCGSGQMKMFQEVSAADAFGPGTEGQVERFETVGMEAATDEG
  MPKSYLPQTVRQGGYMPQ
• Function: Signal-transducing molecule. The receptor systems for IL6, LIF, OSM, CNTF, IL11, CTF1 and BSF3 can utilize IL6ST for initiating signal transmission. Binding of IL6 to IL6R induces IL6ST homodimerization and formation of a high-affinity receptor complex, which activates the intracellular JAK-MAPK and JAK-STAT3 signaling pathways. That causes phosphorylation of IL6ST tyrosine residues which in turn activates STAT3. In parallel, the IL6 signaling pathway induces the expression of two cytokine receptor signaling inhibitors, SOCS1 and SOCS3, which inhibit JAK and terminate the activity of the IL6 signaling pathway as a negative feedback loop. Also activates the yes-associated protein 1 (YAP) and NOTCH pathways to control inflammation-induced epithelial regeneration, independently of STAT3. Acts as a receptor for the neuroprotective peptide humanin as part of a complex with IL27RA/WSX1 and CNTFR. Mediates signals which regulate immune response, hematopoiesis, pain control and bone metabolism. Has a role in embryonic development. Essential for survival of motor and sensory neurons and for differentiation of astrocytes. Required for expression of TRPA1 in nociceptive neurons. Required for the maintenance of PTH1R expression in the osteoblast lineage and for the stimulation of PTH-induced osteoblast differentiation. Required for normal trabecular bone mass and cortical bone composition; [Isoform 2]: Binds to the soluble IL6:sIL6R complex (hyper-IL6), thereby blocking IL6 trans-signaling. Inhibits sIL6R-dependent acute phase response. Also blocks IL11 cluster signaling through IL11R.
• Tissue Specificity: Found in all the tissues and cell lines examined . Expression not restricted to IL6 responsive cells .; [Isoform 2]: Expressed in blood serum (at protein level) .
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  Sig.ling pathways regulating pluripotency of stem cells (hsa04550)
  JAK-STAT sig.ling pathway (hsa04630)
  Th17 cell differentiation (hsa04659)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Coro.virus disease - COVID-19 (hsa05171)
  Pathways in cancer (hsa05200)
  Viral carcinogenesis (hsa05203)
• Reactome Pathway:
  IL-6-type cytokine receptor ligand interactions (R-HSA-6788467)
  Interleukin-35 Signalling (R-HSA-8984722)
  Interleukin-27 signaling (R-HSA-9020956)
  Interleukin-6 signaling (R-HSA-1059683)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Melanoma	DIS1RRCY	Definitive	Biomarker	[1]
Allergy	DIS48ZAP	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Autoimmune disease	DISORMTM	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Cardiac failure	DISDC067	Strong	Biomarker	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[7]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[8]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[9]
Hyper-IgE recurrent infection syndrome 4, autosomal recessive	DISFX7J5	Strong	Autosomal recessive	[10]
Hyper-IgE recurrent infection syndrome 4A, autosomal dominant	DISMIMVO	Strong	Autosomal dominant	[11]
Liver cancer	DISDE4BI	Strong	Biomarker	[12]
Lung cancer	DISCM4YA	Strong	Biomarker	[13]
Lung carcinoma	DISTR26C	Strong	Biomarker	[13]
Myocardial infarction	DIS655KI	Strong	Biomarker	[14]
Myocardial ischemia	DISFTVXF	Strong	Altered Expression	[14]
Neoplasm	DISZKGEW	Strong	Biomarker	[15]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[16]
Osteoarthritis	DIS05URM	Strong	Biomarker	[17]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[18]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[18]
Pituitary tumor	DISN67JD	Strong	Biomarker	[19]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[20]
Pneumonia	DIS8EF3M	Strong	Biomarker	[21]
Pneumonitis	DIS88E0K	Strong	Biomarker	[21]
Prostate cancer	DISF190Y	Strong	Biomarker	[22]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[22]
Systemic sclerosis	DISF44L6	Strong	Altered Expression	[23]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[15]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[15]
Arteriosclerosis	DISK5QGC	moderate	Biomarker	[24]
Atherosclerosis	DISMN9J3	moderate	Biomarker	[24]
Congestive heart failure	DIS32MEA	moderate	Biomarker	[25]
Hepatocellular carcinoma	DIS0J828	moderate	Genetic Variation	[26]
Multiple sclerosis	DISB2WZI	moderate	Biomarker	[27]
Adenocarcinoma	DIS3IHTY	Disputed	Biomarker	[28]
Undifferentiated carcinoma	DISIAZST	Disputed	Biomarker	[29]
Acute myelogenous leukaemia	DISCSPTN	Limited	Altered Expression	[30]
Carcinoma	DISH9F1N	Limited	Genetic Variation	[31]
Colon cancer	DISVC52G	Limited	Biomarker	[32]
Colon carcinoma	DISJYKUO	Limited	Biomarker	[32]
Crohn disease	DIS2C5Q8	Limited	Altered Expression	[33]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Altered Expression	[34]
Obesity	DIS47Y1K	Limited	Biomarker	[35]
Pancreatic cancer	DISJC981	Limited	Biomarker	[36]
Status epilepticus seizure	DISY3BIC	Limited	Biomarker	[37]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Interleukin-6 receptor subunit beta (IL6ST).	[38]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Interleukin-6 receptor subunit beta (IL6ST).	[39]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Interleukin-6 receptor subunit beta (IL6ST).	[40]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Interleukin-6 receptor subunit beta (IL6ST).	[41]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Interleukin-6 receptor subunit beta (IL6ST).	[42]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Interleukin-6 receptor subunit beta (IL6ST).	[43]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Interleukin-6 receptor subunit beta (IL6ST).	[44]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Interleukin-6 receptor subunit beta (IL6ST).	[45]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Interleukin-6 receptor subunit beta (IL6ST).	[46]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Interleukin-6 receptor subunit beta (IL6ST).	[47]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Interleukin-6 receptor subunit beta (IL6ST).	[47]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Interleukin-6 receptor subunit beta (IL6ST).	[8]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Interleukin-6 receptor subunit beta (IL6ST).	[49]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Interleukin-6 receptor subunit beta (IL6ST).	[50]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Interleukin-6 receptor subunit beta (IL6ST).	[51]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Interleukin-6 receptor subunit beta (IL6ST).	[52]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Interleukin-6 receptor subunit beta (IL6ST).	[53]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Interleukin-6 receptor subunit beta (IL6ST).	[54]
Thalidomide	DM70BU5	Approved	Thalidomide decreases the expression of Interleukin-6 receptor subunit beta (IL6ST).	[55]
Lenalidomide	DM6Q7U4	Approved	Lenalidomide decreases the expression of Interleukin-6 receptor subunit beta (IL6ST).	[55]
Rigosertib	DMOSTXF	Phase 3	Rigosertib increases the expression of Interleukin-6 receptor subunit beta (IL6ST).	[56]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Interleukin-6 receptor subunit beta (IL6ST).	[58]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Interleukin-6 receptor subunit beta (IL6ST).	[59]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Interleukin-6 receptor subunit beta (IL6ST).	[60]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the expression of Interleukin-6 receptor subunit beta (IL6ST).	[62]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Interleukin-6 receptor subunit beta (IL6ST).	[63]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Interleukin-6 receptor subunit beta (IL6ST).	[64]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Interleukin-6 receptor subunit beta (IL6ST).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Interleukin-6 receptor subunit beta (IL6ST).	[66]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Interleukin-6 receptor subunit beta (IL6ST).	[67]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Interleukin-6 receptor subunit beta (IL6ST).	[68]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Interleukin-6 receptor subunit beta (IL6ST).	[45]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Interleukin-6 receptor subunit beta (IL6ST).	[57]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Interleukin-6 receptor subunit beta (IL6ST).	[61]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Interleukin-6 receptor subunit beta (IL6ST).	[65]

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