Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA1CPBV)

• DOT Name: Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)
• Synonyms: Death receptor 5; TNF-related apoptosis-inducing ligand receptor 2; TRAIL receptor 2; TRAIL-R2; CD antigen CD262
• Gene Name: TNFRSF10B
• Related Disease: Head-neck squamous cell carcinoma
• UniProt ID: TR10B_HUMAN
• PDB ID: 1D0G; 1D4V; 1DU3; 1ZA3; 2H9G; 3X3F; 4I9X; 4N90; 4OD2; 6NHW; 6NHY; 6T3J; 8DPX
• Pfam ID: PF00531 ; PF00020
• Sequence:
  MEQRGQNAPAASGARKRHGPGPREARGARPGPRVPKTLVLVVAAVLLLVSAESALITQQD
  LAPQQRAAPQQKRSSPSEGLCPPGHHISEDGRDCISCKYGQDYSTHWNDLLFCLRCTRCD
  SGEVELSPCTTTRNTVCQCEEGTFREEDSPEMCRKCRTGCPRGMVKVGDCTPWSDIECVH
  KESGTKHSGEVPAVEETVTSSPGTPASPCSLSGIIIGVTVAAVVLIVAVFVCKSLLWKKV
  LPYLKGICSGGGGDPERVDRSSQRPGAEDNVLNEIVSILQPTQVPEQEMEVQEPAEPTGV
  NMLSPGESEHLLEPAEAERSQRRRLLVPANEGDPTETLRQCFDDFADLVPFDSWEPLMRK
  LGLMDNEIKVAKAEAAGHRDTLYTMLIKWVNKTGRDASVHTLLDALETLGERLAKQKIED
  HLLSSGKFMYLEGNADSAMS
• Function: Receptor for the cytotoxic ligand TNFSF10/TRAIL. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. Promotes the activation of NF-kappa-B. Essential for ER stress-induced apoptosis.
• Tissue Specificity: Widely expressed in adult and fetal tissues; very highly expressed in tumor cell lines such as HeLaS3, K-562, HL-60, SW480, A-549 and G-361; highly expressed in heart, peripheral blood lymphocytes, liver, pancreas, spleen, thymus, prostate, ovary, uterus, placenta, testis, esophagus, stomach and throughout the intestinal tract; not detectable in brain.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  p53 sig.ling pathway (hsa04115)
  Apoptosis (hsa04210)
  Necroptosis (hsa04217)
  .tural killer cell mediated cytotoxicity (hsa04650)
  Pathogenic Escherichia coli infection (hsa05130)
  Salmonella infection (hsa05132)
  Influenza A (hsa05164)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  Cell surface interactions at the vascular wall (R-HSA-202733)
  Regulation by c-FLIP (R-HSA-3371378)
  RIPK1-mediated regulated necrosis (R-HSA-5213460)
  CASP8 activity is inhibited (R-HSA-5218900)
  TP53 Regulates Transcription of Death Receptors and Ligands (R-HSA-6803211)
  Dimerization of procaspase-8 (R-HSA-69416)
  TRAIL signaling (R-HSA-75158)
  Caspase activation via Death Receptors in the presence of ligand (R-HSA-140534)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Head-neck squamous cell carcinoma	DISF7P24	Limited	Autosomal dominant	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[9]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[12]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[13]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[14]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[15]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[16]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[17]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[18]
Selenium	DM25CGV	Approved	Selenium increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[19]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[20]
Folic acid	DMEMBJC	Approved	Folic acid affects the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[21]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[22]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[23]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[24]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[25]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[26]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[27]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[28]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[29]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[30]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[31]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[32]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[15]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[33]
Cidofovir	DMA13GD	Approved	Cidofovir affects the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[34]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[35]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[34]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[34]
Clodronate	DM9Y6X7	Approved	Clodronate affects the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[34]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[36]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[37]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[38]
Acocantherin	DM7JT24	Approved	Acocantherin increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[39]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[40]
Thalidomide	DM70BU5	Approved	Thalidomide decreases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[41]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[40]
Colchicine	DM2POTE	Approved	Colchicine decreases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[8]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[42]
Sorafenib	DMS8IFC	Approved	Sorafenib increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[43]
Ursodeoxycholic acid	DMCUT21	Approved	Ursodeoxycholic acid increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[44]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[34]
Imatinib	DM7RJXL	Approved	Imatinib increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[45]
Dactinomycin	DM2YGNW	Approved	Dactinomycin decreases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[36]
Docetaxel	DMDI269	Approved	Docetaxel increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[32]
Adenine	DMZLHKJ	Approved	Adenine decreases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[8]
Cantharidin	DMBP5N3	Approved	Cantharidin increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[46]
Romidepsin	DMT5GNL	Approved	Romidepsin increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[47]
Chlorambucil	DMRKE63	Approved	Chlorambucil increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[48]
Masoprocol	DMMVNZ0	Approved	Masoprocol increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[49]
Fludarabine	DMVRLT7	Approved	Fludarabine increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[48]
Olaparib	DM8QB1D	Approved	Olaparib increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[50]
Pemetrexed	DMMX2E6	Approved	Pemetrexed increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[51]
Bupropion	DM5PCS7	Approved	Bupropion increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[52]
Vismodegib	DM5IXKQ	Approved	Vismodegib increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[53]
Bepridil	DM0RKS4	Approved	Bepridil increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[54]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[55]
Cibenzoline	DMBG0N4	Phase 4	Cibenzoline increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[54]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[56]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[57]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[58]
EXISULIND	DMBY56U	Phase 3	EXISULIND increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[59]
NVP-LAQ824	DM8JWNA	Phase 3	NVP-LAQ824 increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[60]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[61]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[54]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[62]
Flavopiridol	DMKSUOI	Phase 2	Flavopiridol increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[63]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[64]
LY294002	DMY1AFS	Phase 1	LY294002 increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[65]
AMEP	DMFELMQ	Phase 1	AMEP increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[66]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[67]
PMID26394986-Compound-22	DM43Z1G	Patented	PMID26394986-Compound-22 increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[36]
PMID28870136-Compound-49	DMTUC9E	Patented	PMID28870136-Compound-49 increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[68]
Hydroxyqunoline analog 4	DMGQMCZ	Patented	Hydroxyqunoline analog 4 increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[69]
DUP 697	DMUMAHC	Discontinued in Phase 1	DUP 697 increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[36]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[70]
MG-132	DMKA2YS	Preclinical	MG-132 increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[71]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[72]
Celastrol	DMWQIJX	Preclinical	Celastrol increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[73]
UNC0379	DMD1E4J	Preclinical	UNC0379 increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[74]
Dioscin	DM5H2W9	Preclinical	Dioscin increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[75]
CKI-7	DMV0RFU	Preclinical	CKI-7 increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[76]
NS398	DMINUWH	Terminated	NS398 increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[36]
EMBELIN	DMFZO4Y	Terminated	EMBELIN increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[77]
SC-58125	DM874YU	Terminated	SC-58125 increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[36]
SC-236	DMO1URE	Terminated	SC-236 increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[78]
AA-861	DMPEB0Z	Terminated	AA-861 increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[49]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[79]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[31]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[22]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[80]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B).	[81]

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