Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ8UM8O)

• DOT Name: Tumor necrosis factor receptor superfamily member 8 (TNFRSF8)
• Synonyms: CD30L receptor; Ki-1 antigen; Lymphocyte activation antigen CD30; CD antigen CD30
• Gene Name: TNFRSF8
• UniProt ID: TNR8_HUMAN
• PDB ID: 1D01
• Pfam ID: PF00020
• Sequence:
  MRVLLAALGLLFLGALRAFPQDRPFEDTCHGNPSHYYDKAVRRCCYRCPMGLFPTQQCPQ
  RPTDCRKQCEPDYYLDEADRCTACVTCSRDDLVEKTPCAWNSSRVCECRPGMFCSTSAVN
  SCARCFFHSVCPAGMIVKFPGTAQKNTVCEPASPGVSPACASPENCKEPSSGTIPQAKPT
  PVSPATSSASTMPVRGGTRLAQEAASKLTRAPDSPSSVGRPSSDPGLSPTQPCPEGSGDC
  RKQCEPDYYLDEAGRCTACVSCSRDDLVEKTPCAWNSSRTCECRPGMICATSATNSCARC
  VPYPICAAETVTKPQDMAEKDTTFEAPPLGTQPDCNPTPENGEAPASTSPTQSLLVDSQA
  SKTLPIPTSAPVALSSTGKPVLDAGPVLFWVILVLVVVVGSSAFLLCHRRACRKRIRQKL
  HLCYPVQTSQPKLELVDSRPRRSSTQLRSGASVTEPVAEERGLMSQPLMETCHSVGAAYL
  ESLPLQDASPAGGPSSPRDLPEPRVSTEHTNNKIEKIYIMKADTVIVGTVKAELPEGRGL
  AGPAEPELEEELEADHTPHYPEQETEPPLGSCSDVMLSVEEEGKEDPLPTAASGK
• Function: Receptor for TNFSF8/CD30L. May play a role in the regulation of cellular growth and transformation of activated lymphoblasts. Regulates gene expression through activation of NF-kappa-B.
• Tissue Specificity: .Detected in alveolar macrophages (at protein level).
• 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 8 (TNFRSF8).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Tumor necrosis factor receptor superfamily member 8 (TNFRSF8).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Tumor necrosis factor receptor superfamily member 8 (TNFRSF8).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Tumor necrosis factor receptor superfamily member 8 (TNFRSF8).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Tumor necrosis factor receptor superfamily member 8 (TNFRSF8).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Tumor necrosis factor receptor superfamily member 8 (TNFRSF8).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Tumor necrosis factor receptor superfamily member 8 (TNFRSF8).	[2]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Tumor necrosis factor receptor superfamily member 8 (TNFRSF8).	[6]
Quinidine	DMLPICK	Approved	Quinidine decreases the expression of Tumor necrosis factor receptor superfamily member 8 (TNFRSF8).	[2]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Tumor necrosis factor receptor superfamily member 8 (TNFRSF8).	[7]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Tumor necrosis factor receptor superfamily member 8 (TNFRSF8).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Tumor necrosis factor receptor superfamily member 8 (TNFRSF8).	[10]
Aphidicolin	DM71C6D	Discontinued in Phase 1	Aphidicolin increases the expression of Tumor necrosis factor receptor superfamily member 8 (TNFRSF8).	[2]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Tumor necrosis factor receptor superfamily member 8 (TNFRSF8).	[11]
CATECHIN	DMY38SB	Investigative	CATECHIN decreases the expression of Tumor necrosis factor receptor superfamily member 8 (TNFRSF8).	[12]

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] HL60 cells halted in G1 or S phase differentiate normally. Exp Cell Res. 2002 Nov 15;281(1):28-38. doi: 10.1006/excr.2002.5654.
• [3] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] 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.
• [5] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [6] 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.
• [7] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [8] Expression of CD30 mRNA, CD30L mRNA and a variant form of CD30 mRNA in restimulated peripheral blood mononuclear cells (PBMC) of patients with helminthic infections resembling a Th2 disease. Clin Exp Immunol. 1999 Jan;115(1):114-9. doi: 10.1046/j.1365-2249.1999.00774.x.
• [9] 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.
• [10] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [11] Microarray Analysis of Gene Expression Alteration in Human Middle Ear Epithelial Cells Induced by Asian Sand Dust. Clin Exp Otorhinolaryngol. 2015 Dec;8(4):345-53. doi: 10.3342/ceo.2015.8.4.345. Epub 2015 Nov 10.
• [12] Epicatechin and a cocoa polyphenolic extract modulate gene expression in human Caco-2 cells. J Nutr. 2004 Oct;134(10):2509-16.