Details of Drug Off-Target (DOT)

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

• DOT Name: Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D)
• Synonyms: Decoy receptor 2; DcR2; TNF-related apoptosis-inducing ligand receptor 4; TRAIL receptor 4; TRAIL-R4; TRAIL receptor with a truncated death domain; CD antigen CD264
• Gene Name: TNFRSF10D
• Related Disease:
  Familial hypercholesterolemia
  Multiple sclerosis
  Non-small-cell lung cancer
  Advanced cancer
  Breast carcinoma
  Breast neoplasm
  Cervical cancer
  Cervical carcinoma
  Chronic kidney disease
  Colon cancer
  Colon carcinoma
  Diabetic kidney disease
  Head and neck cancer
  Head and neck carcinoma
  Hyperplasia
  IgA nephropathy
  Immunodeficiency
  leukaemia
  Leukemia
  Malignant mesothelioma
  Pancreatic cancer
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Breast cancer
  Metastatic sarcoma
  Uveal Melanoma
  Melanoma
  Acute myelogenous leukaemia
  Chromosomal disorder
  Chronic pancreatitis
  MALT lymphoma
  Neuroblastoma
  Plasma cell myeloma
  Promyelocytic leukaemia
• UniProt ID: TR10D_HUMAN
• Pfam ID: PF00020
• Sequence:
  MGLWGQSVPTASSARAGRYPGARTASGTRPWLLDPKILKFVVFIVAVLLPVRVDSATIPR
  QDEVPQQTVAPQQQRRSLKEEECPAGSHRSEYTGACNPCTEGVDYTIASNNLPSCLLCTV
  CKSGQTNKSSCTTTRDTVCQCEKGSFQDKNSPEMCRTCRTGCPRGMVKVSNCTPRSDIKC
  KNESAASSTGKTPAAEETVTTILGMLASPYHYLIIIVVLVIILAVVVVGFSCRKKFISYL
  KGICSGGGGGPERVHRVLFRRRSCPSRVPGAEDNARNETLSNRYLQPTQVSEQEIQGQEL
  AELTGVTVELPEEPQRLLEQAEAEGCQRRRLLVPVNDADSADISTLLDASATLEEGHAKE
  TIQDQLVGSEKLFYEEDEAGSATSCL
• Function: Receptor for the cytotoxic ligand TRAIL. Contains a truncated death domain and hence is not capable of inducing apoptosis but protects against TRAIL-mediated apoptosis. Reports are contradictory with regards to its ability to induce the NF-kappa-B pathway. According to PubMed:9382840, it cannot but according to PubMed:9430226, it can induce the NF-kappa-B pathway.
• Tissue Specificity: Widely expressed, in particular in fetal kidney, lung and liver, and in adult testis and liver. Also expressed in peripheral blood leukocytes, colon and small intestine, ovary, prostate, thymus, spleen, pancreas, kidney, lung, placenta and heart.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
• Reactome Pathway:
  TP53 Regulates Transcription of Death Receptors and Ligands (R-HSA-6803211)
  TRAIL signaling (R-HSA-75158)
  Cell surface interactions at the vascular wall (R-HSA-202733)

Molecular Interaction Atlas (MIA) of This DOT

35 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Familial hypercholesterolemia	DISC06IX	Definitive	Biomarker	[1]
Multiple sclerosis	DISB2WZI	Definitive	Biomarker	[2]
Non-small-cell lung cancer	DIS5Y6R9	Definitive	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[6]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[7]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[7]
Chronic kidney disease	DISW82R7	Strong	Biomarker	[8]
Colon cancer	DISVC52G	Strong	Altered Expression	[9]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[9]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[10]
Head and neck cancer	DISBPSQZ	Strong	Biomarker	[11]
Head and neck carcinoma	DISOU1DS	Strong	Biomarker	[11]
Hyperplasia	DISK4DFB	Strong	Biomarker	[12]
IgA nephropathy	DISZ8MTK	Strong	Biomarker	[13]
Immunodeficiency	DIS093I0	Strong	Genetic Variation	[14]
leukaemia	DISS7D1V	Strong	Genetic Variation	[15]
Leukemia	DISNAKFL	Strong	Genetic Variation	[15]
Malignant mesothelioma	DISTHJGH	Strong	Posttranslational Modification	[15]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[16]
Prostate cancer	DISF190Y	Strong	Altered Expression	[17]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[17]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[18]
Breast cancer	DIS7DPX1	moderate	Biomarker	[5]
Metastatic sarcoma	DISKYC7V	moderate	Biomarker	[19]
Uveal Melanoma	DISA7ZGL	moderate	Biomarker	[20]
Melanoma	DIS1RRCY	Disputed	Posttranslational Modification	[21]
Acute myelogenous leukaemia	DISCSPTN	Limited	Altered Expression	[22]
Chromosomal disorder	DISM5BB5	Limited	Altered Expression	[23]
Chronic pancreatitis	DISBUOMJ	Limited	Biomarker	[24]
MALT lymphoma	DIS1AVVE	Limited	Altered Expression	[23]
Neuroblastoma	DISVZBI4	Limited	Posttranslational Modification	[25]
Plasma cell myeloma	DIS0DFZ0	Limited	Biomarker	[26]
Promyelocytic leukaemia	DISYGG13	Limited	Altered Expression	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[27]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[28]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[29]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[30]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[31]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[32]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[33]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[34]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[35]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[36]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[37]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[27]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[38]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[39]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[40]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[41]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[42]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[43]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[44]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[45]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[46]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[47]
PEITC	DMOMN31	Phase 2	PEITC increases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[48]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[49]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[50]
PF-3758309	DM36PKZ	Phase 1	PF-3758309 decreases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[51]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[52]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[53]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[54]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[40]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[56]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[57]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[58]
CH-223191	DMMJZYC	Investigative	CH-223191 decreases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[59]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl decreases the expression of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[60]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Tumor necrosis factor receptor superfamily member 10D (TNFRSF10D).	[55]

References

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