Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCW8HT6)

• DOT Name: Tumor necrosis factor receptor superfamily member 18 (TNFRSF18)
• Synonyms: Activation-inducible TNFR family receptor; Glucocorticoid-induced TNFR-related protein; CD antigen CD357
• Gene Name: TNFRSF18
• UniProt ID: TNR18_HUMAN
• PDB ID: 7KHD; 7LAW
• Sequence:
  MAQHGAMGAFRALCGLALLCALSLGQRPTGGPGCGPGRLLLGTGTDARCCRVHTTRCCRD
  YPGEECCSEWDCMCVQPEFHCGDPCCTTCRHHPCPPGQGVQSQGKFSFGFQCIDCASGTF
  SGGHEGHCKPWTDCTQFGFLTVFPGNKTHNAVCVPGSPPAEPLGWLTVVLLAVAACVLLL
  TSAQLGLHIWQLRSQCMWPRETQLLLEVPPSTEDARSCQFPEEERGERSAEEKGRLGDLW
  V
• Function: Receptor for TNFSF18. Seems to be involved in interactions between activated T-lymphocytes and endothelial cells and in the regulation of T-cell receptor-mediated cell death. Mediated NF-kappa-B activation via the TRAF2/NIK pathway.
• Tissue Specificity: Expressed in lymph node, peripheral blood leukocytes and weakly in spleen.
• KEGG Pathway: Cytokine-cytokine receptor interaction (hsa04060)
• Reactome Pathway:
  RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs) (R-HSA-8877330)
  TNFs bind their physiological receptors (R-HSA-5669034)

Molecular Interaction Atlas (MIA) of This DOT

4 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 18 (TNFRSF18).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Tumor necrosis factor receptor superfamily member 18 (TNFRSF18).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Tumor necrosis factor receptor superfamily member 18 (TNFRSF18).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Tumor necrosis factor receptor superfamily member 18 (TNFRSF18).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Tumor necrosis factor receptor superfamily member 18 (TNFRSF18).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Tumor necrosis factor receptor superfamily member 18 (TNFRSF18).	[4]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Tumor necrosis factor receptor superfamily member 18 (TNFRSF18).	[5]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Tumor necrosis factor receptor superfamily member 18 (TNFRSF18).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Tumor necrosis factor receptor superfamily member 18 (TNFRSF18).	[8]

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] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] Apoptosis-related mRNA expression profiles of ovarian cancer cell lines following cisplatin treatment. J Gynecol Oncol. 2010 Dec 30;21(4):255-61. doi: 10.3802/jgo.2010.21.4.255. Epub 2010 Dec 31.
• [4] Arsenic trioxide induces different gene expression profiles of genes related to growth and apoptosis in glioma cells dependent on the p53 status. Mol Biol Rep. 2008 Sep;35(3):421-9.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Transcriptional profiling of MCF7 breast cancer cells in response to 5-Fluorouracil: relationship with cell cycle changes and apoptosis, and identification of novel targets of p53. Int J Cancer. 2006 Sep 1;119(5):1164-75.
• [7] 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.
• [8] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [9] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.