Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDS2EAR)

• DOT Name: Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B)
• Synonyms: Tumor necrosis factor receptor 2; TNF-R2; Tumor necrosis factor receptor type II; TNF-RII; TNFR-II; p75; p80 TNF-alpha receptor; CD antigen CD120b; Etanercept
• Gene Name: TNFRSF1B
• UniProt ID: TNR1B_HUMAN
• PDB ID: 1CA9; 3ALQ; 8HLB
• Pfam ID: PF00020
• Sequence:
  MAPVAVWAALAVGLELWAAAHALPAQVAFTPYAPEPGSTCRLREYYDQTAQMCCSKCSPG
  QHAKVFCTKTSDTVCDSCEDSTYTQLWNWVPECLSCGSRCSSDQVETQACTREQNRICTC
  RPGWYCALSKQEGCRLCAPLRKCRPGFGVARPGTETSDVVCKPCAPGTFSNTTSSTDICR
  PHQICNVVAIPGNASMDAVCTSTSPTRSMAPGAVHLPQPVSTRSQHTQPTPEPSTAPSTS
  FLLPMGPSPPAEGSTGDFALPVGLIVGVTALGLLIIGVVNCVIMTQVKKKPLCLQREAKV
  PHLPADKARGTQGPEQQHLLITAPSSSSSSLESSASALDRRAPTRNQPQAPGVEASGAGE
  ARASTGSSDSSPGGHGTQVNVTCIVNVCSSSDHSSQCSSQASSTMGDTDSSPSESPKDEQ
  VPFSKEECAFRSQLETPETLLGSTEEKPLPLGVPDAGMKPS
• Function: Receptor with high affinity for TNFSF2/TNF-alpha and approximately 5-fold lower affinity for homotrimeric TNFSF1/lymphotoxin-alpha. The TRAF1/TRAF2 complex recruits the apoptotic suppressors BIRC2 and BIRC3 to TNFRSF1B/TNFR2. This receptor mediates most of the metabolic effects of TNF-alpha. Isoform 2 blocks TNF-alpha-induced apoptosis, which suggests that it regulates TNF-alpha function by antagonizing its biological activity.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  TNF sig.ling pathway (hsa04668)
  Adipocytokine sig.ling pathway (hsa04920)
  Amyotrophic lateral sclerosis (hsa05014)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Human immunodeficiency virus 1 infection (hsa05170)
• Reactome Pathway:
  TNFs bind their physiological receptors (R-HSA-5669034)
  Interleukin-10 signaling (R-HSA-6783783)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  Neutrophil degranulation (R-HSA-6798695)
  TNFR2 non-canonical NF-kB pathway (R-HSA-5668541)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydrogen peroxide	DM1NG5W	Approved	Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) decreases the response to substance of Hydrogen peroxide.	[29]
Fluorouracil	DMUM7HZ	Approved	Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) affects the response to substance of Fluorouracil.	[30]

28 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 Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B).	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B).	[10]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B).	[11]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B).	[12]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B).	[13]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid increases the expression of Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B).	[14]
Thalidomide	DM70BU5	Approved	Thalidomide decreases the expression of Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B).	[15]
Gefitinib	DM15F0X	Approved	Gefitinib decreases the expression of Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B).	[16]
Lenalidomide	DM6Q7U4	Approved	Lenalidomide decreases the expression of Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B).	[15]
Alfacalcidol	DM1237M	Phase 4	Alfacalcidol decreases the expression of Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B).	[17]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B).	[18]
Sodium stibogluconate	DMH5MVE	Phase 2	Sodium stibogluconate decreases the expression of Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B).	[19]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B).	[22]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B).	[23]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B).	[24]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B).	[25]
Aminohippuric acid	DMUN54G	Investigative	Aminohippuric acid increases the expression of Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B).	[26]
Beta-D-Glucose	DM5IHYP	Investigative	Beta-D-Glucose increases the expression of Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B).	[18]
Aloe-emodin	DMPTY8S	Investigative	Aloe-emodin increases the expression of Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B).	[27]
Dimethylallyl Diphosphate	DMP5I47	Investigative	Dimethylallyl Diphosphate increases the expression of Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B).	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic decreases the methylation of Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B).	[20]

References

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• [19] Soluble receptors for tumor necrosis factor as markers of disease activity in visceral leishmaniasis. J Infect Dis. 1995 Feb;171(2):498-501. doi: 10.1093/infdis/171.2.498.
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