Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2HVZGV)

• DOT Name: Tumor necrosis factor receptor superfamily member 3 (LTBR)
• Synonyms: Lymphotoxin-beta receptor; Tumor necrosis factor C receptor; Tumor necrosis factor receptor 2-related protein; Tumor necrosis factor receptor type III; TNF-RIII; TNFR-III
• Gene Name: LTBR
• UniProt ID: TNR3_HUMAN
• PDB ID: 1RF3; 4MXW
• Pfam ID: PF00020
• Sequence:
  MLLPWATSAPGLAWGPLVLGLFGLLAASQPQAVPPYASENQTCRDQEKEYYEPQHRICCS
  RCPPGTYVSAKCSRIRDTVCATCAENSYNEHWNYLTICQLCRPCDPVMGLEEIAPCTSKR
  KTQCRCQPGMFCAAWALECTHCELLSDCPPGTEAELKDEVGKGNNHCVPCKAGHFQNTSS
  PSARCQPHTRCENQGLVEAAPGTAQSDTTCKNPLEPLPPEMSGTMLMLAVLLPLAFFLLL
  ATVFSCIWKSHPSLCRKLGSLLKRRPQGEGPNPVAGSWEPPKAHPYFPDLVQPLLPISGD
  VSPVSTGLPAAPVLEAGVPQQQSPLDLTREPQLEPGEQSQVAHGTNGIHVTGGSMTITGN
  IYIYNGPVLGGPPGPGDLPATPEPPYPIPEEGDPGPPGLSTPHQEDGKAWHLAETEHCGA
  TPSNRGPRNQFITHD
• Function: Receptor for the heterotrimeric lymphotoxin containing LTA and LTB, and for TNFS14/LIGHT. Promotes apoptosis via TRAF3 and TRAF5. May play a role in the development of lymphoid organs.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  NF-kappa B sig.ling pathway (hsa04064)
  HIF-1 sig.ling pathway (hsa04066)
  Intesti.l immune network for IgA production (hsa04672)
  Human T-cell leukemia virus 1 infection (hsa05166)
  Viral carcinogenesis (hsa05203)
• Reactome Pathway:
  TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway (R-HSA-5676594)
  TNFR2 non-canonical NF-kB pathway (R-HSA-5668541)

Molecular Interaction Atlas (MIA) of This DOT

15 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 3 (LTBR).	[1]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Tumor necrosis factor receptor superfamily member 3 (LTBR).	[2]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Tumor necrosis factor receptor superfamily member 3 (LTBR).	[3]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Tumor necrosis factor receptor superfamily member 3 (LTBR).	[4]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Tumor necrosis factor receptor superfamily member 3 (LTBR).	[5]
Selenium	DM25CGV	Approved	Selenium increases the expression of Tumor necrosis factor receptor superfamily member 3 (LTBR).	[6]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Tumor necrosis factor receptor superfamily member 3 (LTBR).	[7]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Tumor necrosis factor receptor superfamily member 3 (LTBR).	[2]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Tumor necrosis factor receptor superfamily member 3 (LTBR).	[8]
Ibuprofen	DM8VCBE	Approved	Ibuprofen decreases the expression of Tumor necrosis factor receptor superfamily member 3 (LTBR).	[9]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline increases the expression of Tumor necrosis factor receptor superfamily member 3 (LTBR).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Tumor necrosis factor receptor superfamily member 3 (LTBR).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Tumor necrosis factor receptor superfamily member 3 (LTBR).	[13]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Tumor necrosis factor receptor superfamily member 3 (LTBR).	[14]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Tumor necrosis factor receptor superfamily member 3 (LTBR).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Tumor necrosis factor receptor superfamily member 3 (LTBR).	[11]

References

• [1] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [2] Estrogen regulation of apoptosis in osteoblasts. Physiol Behav. 2010 Feb 9;99(2):181-5. doi: 10.1016/j.physbeh.2009.04.025. Epub 2009 May 5.
• [3] 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.
• [4] Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
• [5] 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.
• [6] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [7] Rosiglitazone sensitizes MDA-MB-231 breast cancer cells to anti-tumour effects of tumour necrosis factor-alpha, CH11 and CYC202. Endocr Relat Cancer. 2007 Jun;14(2):305-15. doi: 10.1677/ERC-06-0003.
• [8] 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.
• [9] Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain. Pain. 2007 Mar;128(1-2):136-47.
• [10] Controlled diesel exhaust and allergen coexposure modulates microRNA and gene expression in humans: Effects on inflammatory lung markers. J Allergy Clin Immunol. 2016 Dec;138(6):1690-1700. doi: 10.1016/j.jaci.2016.02.038. Epub 2016 Apr 24.
• [11] 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.
• [12] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [13] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [14] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [15] 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.