Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU2OTLL)

• DOT Name: Trophoblast glycoprotein (TPBG)
• Synonyms: 5T4 oncofetal antigen; 5T4 oncofetal trophoblast glycoprotein; 5T4 oncotrophoblast glycoprotein; M6P1; Wnt-activated inhibitory factor 1; WAIF1
• Gene Name: TPBG
• UniProt ID: TPBG_HUMAN
• PDB ID: 4CNC; 4CNM; 6HBY
• Pfam ID: PF13855 ; PF01463 ; PF01462
• Sequence:
  MPGGCSRGPAAGDGRLRLARLALVLLGWVSSSSPTSSASSFSSSAPFLASAVSAQPPLPD
  QCPALCECSEAARTVKCVNRNLTEVPTDLPAYVRNLFLTGNQLAVLPAGAFARRPPLAEL
  AALNLSGSRLDEVRAGAFEHLPSLRQLDLSHNPLADLSPFAFSGSNASVSAPSPLVELIL
  NHIVPPEDERQNRSFEGMVVAALLAGRALQGLRRLELASNHFLYLPRDVLAQLPSLRHLD
  LSNNSLVSLTYVSFRNLTHLESLHLEDNALKVLHNGTLAELQGLPHIRVFLDNNPWVCDC
  HMADMVTWLKETEVVQGKDRLTCAYPEKMRNRVLLELNSADLDCDPILPPSLQTSYVFLG
  IVLALIGAIFLLVLYLNRKGIKKWMHNIRDACRDHMEGYHYRYEINADPRLTNLSSNSDV
• Function: May function as an inhibitor of Wnt/beta-catenin signaling by indirectly interacting with LRP6 and blocking Wnt3a-dependent LRP6 internalization.
• Tissue Specificity: Expressed by all types of trophoblasts as early as 9 weeks of development. Specific for trophoblastic cells except for amniotic epithelium. In adult tissues, the expression is limited to a few epithelial cell types but is found on a variety of carcinoma.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Trophoblast glycoprotein (TPBG).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Trophoblast glycoprotein (TPBG).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Trophoblast glycoprotein (TPBG).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Trophoblast glycoprotein (TPBG).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Trophoblast glycoprotein (TPBG).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Trophoblast glycoprotein (TPBG).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Trophoblast glycoprotein (TPBG).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Trophoblast glycoprotein (TPBG).	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Trophoblast glycoprotein (TPBG).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Trophoblast glycoprotein (TPBG).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Trophoblast glycoprotein (TPBG).	[12]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Trophoblast glycoprotein (TPBG).	[13]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Trophoblast glycoprotein (TPBG).	[14]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Trophoblast glycoprotein (TPBG).	[15]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Trophoblast glycoprotein (TPBG).	[16]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Trophoblast glycoprotein (TPBG).	[17]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Trophoblast glycoprotein (TPBG).	[18]
APR-246	DMNFADH	Phase 2	APR-246 affects the expression of Trophoblast glycoprotein (TPBG).	[19]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Trophoblast glycoprotein (TPBG).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Trophoblast glycoprotein (TPBG).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Trophoblast glycoprotein (TPBG).	[20]

References

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• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
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• [10] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [11] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [12] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [13] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [14] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [15] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [16] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [17] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [18] 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.
• [19] Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis. Oncogene. 2010 Mar 4;29(9):1329-38. doi: 10.1038/onc.2009.425. Epub 2009 Nov 30.
• [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] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.