Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVZ7I3A)

• DOT Name: Tumor necrosis factor receptor superfamily member 25 (TNFRSF25)
• Synonyms: Apo-3; Apoptosis-inducing receptor AIR; Apoptosis-mediating receptor DR3; Apoptosis-mediating receptor TRAMP; Death receptor 3; Lymphocyte-associated receptor of death; LARD; Protein WSL; Protein WSL-1
• Gene Name: TNFRSF25
• UniProt ID: TNR25_HUMAN
• PDB ID: 5YGP; 5YGS
• Pfam ID: PF00531 ; PF00020
• Sequence:
  MEQRPRGCAAVAAALLLVLLGARAQGGTRSPRCDCAGDFHKKIGLFCCRGCPAGHYLKAP
  CTEPCGNSTCLVCPQDTFLAWENHHNSECARCQACDEQASQVALENCSAVADTRCGCKPG
  WFVECQVSQCVSSSPFYCQPCLDCGALHRHTRLLCSRRDTDCGTCLPGFYEHGDGCVSCP
  TSTLGSCPERCAAVCGWRQMFWVQVLLAGLVVPLLLGATLTYTYRHCWPHKPLVTADEAG
  MEALTPPPATHLSPLDSAHTLLAPPDSSEKICTVQLVGNSWTPGYPETQEALCPQVTWSW
  DQLPSRALGPAAAPTLSPESPAGSPAMMLQPGPQLYDVMDAVPARRWKEFVRTLGLREAE
  IEAVEVEIGRFRDQQYEMLKRWRQQQPAGLGAVYAALERMGLDGCVEDLRSRLQRGP
• Function: Receptor for TNFSF12/APO3L/TWEAK. Interacts directly with the adapter TRADD. Mediates activation of NF-kappa-B and induces apoptosis. May play a role in regulating lymphocyte homeostasis.
• Tissue Specificity: Abundantly expressed in thymocytes and lymphocytes. Detected in lymphocyte-rich tissues such as thymus, colon, intestine, and spleen. Also found in the prostate.
• KEGG Pathway: Cytokine-cytokine receptor interaction (hsa04060)
• Reactome Pathway: TNFs bind their physiological receptors (R-HSA-5669034)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Tumor necrosis factor receptor superfamily member 25 (TNFRSF25).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Tumor necrosis factor receptor superfamily member 25 (TNFRSF25).	[20]

26 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 25 (TNFRSF25).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Tumor necrosis factor receptor superfamily member 25 (TNFRSF25).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tumor necrosis factor receptor superfamily member 25 (TNFRSF25).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Tumor necrosis factor receptor superfamily member 25 (TNFRSF25).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Tumor necrosis factor receptor superfamily member 25 (TNFRSF25).	[6]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Tumor necrosis factor receptor superfamily member 25 (TNFRSF25).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Tumor necrosis factor receptor superfamily member 25 (TNFRSF25).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Tumor necrosis factor receptor superfamily member 25 (TNFRSF25).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Tumor necrosis factor receptor superfamily member 25 (TNFRSF25).	[10]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Tumor necrosis factor receptor superfamily member 25 (TNFRSF25).	[11]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Tumor necrosis factor receptor superfamily member 25 (TNFRSF25).	[12]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Tumor necrosis factor receptor superfamily member 25 (TNFRSF25).	[13]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Tumor necrosis factor receptor superfamily member 25 (TNFRSF25).	[14]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Tumor necrosis factor receptor superfamily member 25 (TNFRSF25).	[15]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Tumor necrosis factor receptor superfamily member 25 (TNFRSF25).	[16]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Tumor necrosis factor receptor superfamily member 25 (TNFRSF25).	[17]
Hesperidin	DMI5DW1	Approved	Hesperidin increases the expression of Tumor necrosis factor receptor superfamily member 25 (TNFRSF25).	[18]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Tumor necrosis factor receptor superfamily member 25 (TNFRSF25).	[19]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Tumor necrosis factor receptor superfamily member 25 (TNFRSF25).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Tumor necrosis factor receptor superfamily member 25 (TNFRSF25).	[21]
Dioscin	DM5H2W9	Preclinical	Dioscin increases the expression of Tumor necrosis factor receptor superfamily member 25 (TNFRSF25).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Tumor necrosis factor receptor superfamily member 25 (TNFRSF25).	[14]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Tumor necrosis factor receptor superfamily member 25 (TNFRSF25).	[23]
Manganese	DMKT129	Investigative	Manganese increases the expression of Tumor necrosis factor receptor superfamily member 25 (TNFRSF25).	[24]
Morin	DM2OGZ5	Investigative	Morin increases the expression of Tumor necrosis factor receptor superfamily member 25 (TNFRSF25).	[25]
LICOAGROCHACONE A	DMWY0TN	Investigative	LICOAGROCHACONE A increases the expression of Tumor necrosis factor receptor superfamily member 25 (TNFRSF25).	[26]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Doxorubicin induces cell senescence preferentially over apoptosis in the FU-SY-1 synovial sarcoma cell line. J Orthop Res. 2006 Jun;24(6):1163-9. doi: 10.1002/jor.20169.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Comparative effects of raloxifene, tamoxifen and estradiol on human osteoblasts in vitro: estrogen receptor dependent or independent pathways of raloxifene. J Steroid Biochem Mol Biol. 2009 Feb;113(3-5):281-9.
• [7] Pattern of expression of apoptosis and inflammatory genes in humans exposed to arsenic and/or fluoride. Sci Total Environ. 2010 Jan 15;408(4):760-7. doi: 10.1016/j.scitotenv.2009.11.016. Epub 2009 Dec 4.
• [8] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [9] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [10] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [11] Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
• [12] Effect of zoledronic acid on oral fibroblasts and epithelial cells: a potential mechanism of bisphosphonate-associated osteonecrosis. Br J Haematol. 2009 Mar;144(5):667-76. doi: 10.1111/j.1365-2141.2008.07504.x. Epub 2008 Nov 20.
• [13] Survival of retinal pigment epithelium after exposure to prolonged oxidative injury: a detailed gene expression and cellular analysis. Invest Ophthalmol Vis Sci. 2004 Oct;45(10):3767-77.
• [14] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [15] Lunasin, a novel seed peptide, sensitizes human breast cancer MDA-MB-231 cells to aspirin-arrested cell cycle and induced apoptosis. Chem Biol Interact. 2010 Jul 30;186(2):127-34. doi: 10.1016/j.cbi.2010.04.027. Epub 2010 May 21.
• [16] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [17] Triggering of transient receptor potential vanilloid type 1 (TRPV1) by capsaicin induces Fas/CD95-mediated apoptosis of urothelial cancer cells in an ATM-dependent manner. Carcinogenesis. 2009 Aug;30(8):1320-9. doi: 10.1093/carcin/bgp138. Epub 2009 Jun 5.
• [18] Mangiferin has an additive effect on the apoptotic properties of hesperidin in Cyclopia sp. tea extracts. PLoS One. 2014 Mar 14;9(3):e92128. doi: 10.1371/journal.pone.0092128. eCollection 2014.
• [19] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [20] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [21] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [22] Molecular mechanism and inhibitory targets of dioscin in HepG2 cells. Food Chem Toxicol. 2018 Oct;120:143-154.
• [23] Identification of genes associated with paraquat-induced toxicity in SH-SY5Y cells by PCR array focused on apoptotic pathways. J Toxicol Environ Health A. 2008;71(22):1457-67. doi: 10.1080/15287390802329364.
• [24] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.
• [25] Molecular mechanism of anti-cancerous potential of Morin extracted from mulberry in Hela cells. Food Chem Toxicol. 2018 Feb;112:466-475. doi: 10.1016/j.fct.2017.07.002. Epub 2017 Jul 6.
• [26] Licochalcone A from licorice root, an inhibitor of human hepatoma cell growth via induction of cell apoptosis and cell cycle arrest. Food Chem Toxicol. 2018 Oct;120:407-417. doi: 10.1016/j.fct.2018.07.044. Epub 2018 Jul 25.