Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7WFW4U)

• DOT Name: Oxytocin receptor (OXTR)
• Synonyms: OT-R
• Gene Name: OXTR
• UniProt ID: OXYR_HUMAN
• PDB ID: 6TPK; 7QVM; 7RYC
• Pfam ID: PF00001
• Sequence:
  MEGALAANWSAEAANASAAPPGAEGNRTAGPPRRNEALARVEVAVLCLILLLALSGNACV
  LLALRTTRQKHSRLFFFMKHLSIADLVVAVFQVLPQLLWDITFRFYGPDLLCRLVKYLQV
  VGMFASTYLLLLMSLDRCLAICQPLRSLRRRTDRLAVLATWLGCLVASAPQVHIFSLREV
  ADGVFDCWAVFIQPWGPKAYITWITLAVYIVPVIVLAACYGLISFKIWQNLRLKTAAAAA
  AEAPEGAAAGDGGRVALARVSSVKLISKAKIRTVKMTFIIVLAFIVCWTPFFFVQMWSVW
  DANAPKEASAFIIVMLLASLNSCCNPWIYMLFTGHLFHELVQRFLCCSASYLKGRRLGET
  SASKKSNSSSFVLSHRSSSQRSCSQPSTA
• Function: Receptor for oxytocin. The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system.
• KEGG Pathway:
  Calcium sig.ling pathway (hsa04020)
  cAMP sig.ling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  Oxytocin sig.ling pathway (hsa04921)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Vasopressin-like receptors (R-HSA-388479)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Oxytocin receptor (OXTR) decreases the response to substance of Doxorubicin.	[18]
Peginterferon alfa-2b	DMAP58Y	Approved	Oxytocin receptor (OXTR) increases the Gastrointestinal disorders ADR of Peginterferon alfa-2b.	[19]
Methylenedioxymethamphetamine	DMYVU47	Investigative	Oxytocin receptor (OXTR) affects the response to substance of Methylenedioxymethamphetamine.	[20]

17 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 Oxytocin receptor (OXTR).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Oxytocin receptor (OXTR).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Oxytocin receptor (OXTR).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Oxytocin receptor (OXTR).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Oxytocin receptor (OXTR).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Oxytocin receptor (OXTR).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Oxytocin receptor (OXTR).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Oxytocin receptor (OXTR).	[8]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Oxytocin receptor (OXTR).	[9]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Oxytocin receptor (OXTR).	[10]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Oxytocin receptor (OXTR).	[11]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Oxytocin receptor (OXTR).	[12]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Oxytocin receptor (OXTR).	[13]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Oxytocin receptor (OXTR).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Oxytocin receptor (OXTR).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Oxytocin receptor (OXTR).	[17]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Oxytocin receptor (OXTR).	[5]

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 decreases the methylation of Oxytocin receptor (OXTR).	[14]

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] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [6] 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.
• [7] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [8] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [9] Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
• [10] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [11] Differential regulation of the p73 cistrome by mammalian target of rapamycin reveals transcriptional programs of mesenchymal differentiation and tumorigenesis. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2076-81. doi: 10.1073/pnas.1011936108. Epub 2011 Jan 18.
• [12] A high concentration of genistein down-regulates activin A, Smad3 and other TGF-beta pathway genes in human uterine leiomyoma cells. Exp Mol Med. 2012 Apr 30;44(4):281-92.
• [13] Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
• [14] 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.
• [15] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [16] 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.
• [17] 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.
• [18] Gene expression and amplification in breast carcinoma cells with intrinsic and acquired doxorubicin resistance. Oncogene. 2001 Mar 15;20(11):1300-6. doi: 10.1038/sj.onc.1204235.
• [19] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [20] Oxytocin receptor gene variations and socio-emotional effects of MDMA: A pooled analysis of controlled studies in healthy subjects. PLoS One. 2018 Jun 18;13(6):e0199384. doi: 10.1371/journal.pone.0199384. eCollection 2018.