Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT48M72Z)

• DOT Name: Oxytocin-neurophysin 1 (OXT)
• Synonyms: OT-NPI
• Gene Name: OXT
• Related Disease:
  Acute myocardial infarction
  Alcohol dependence
  Alzheimer disease
  Anxiety disorder
  Autism
  Autism spectrum disorder
  Dementia
  Depression
  Disseminated intravascular coagulation
  Epilepsy with generalized tonic-clonic seizures
  Hypotension
  Irritable bowel syndrome
  Major depressive disorder
  Neuroblastoma
  Osteosarcoma
  Prostate disease
  Schizophrenia
  Gastric ulcer
  Mood disorder
  High blood pressure
  Breast cancer
  Breast carcinoma
  Carcinoma
  Colon cancer
  Colonic neoplasm
  Conduct disorder
  Ischemia
  Undifferentiated carcinoma
• UniProt ID: NEU1_HUMAN
• PDB ID: 7OFG; 7OTD; 7QVM; 7RYC
• Pfam ID: PF00220 ; PF00184
• Sequence:
  MAGPSLACCLLGLLALTSACYIQNCPLGGKRAAPDLDVRKCLPCGPGGKGRCFGPNICCA
  EELGCFVGTAEALRCQEENYLPSPCQSGQKACGSGGRCAVLGLCCSPDGCHADPACDAEA
  TFSQR
• Function: Neurophysin 1 specifically binds oxytocin.; Oxytocin causes contraction of the smooth muscle of the uterus and of the mammary gland. Acts by binding to oxytocin receptor (OXTR).
• KEGG Pathway:
  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

28 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myocardial infarction	DISE3HTG	Strong	Biomarker	[1]
Alcohol dependence	DIS4ZSCO	Strong	Genetic Variation	[2]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[3]
Anxiety disorder	DISBI2BT	Strong	Therapeutic	[4]
Autism	DISV4V1Z	Strong	Genetic Variation	[5]
Autism spectrum disorder	DISXK8NV	Strong	Altered Expression	[6]
Dementia	DISXL1WY	Strong	Genetic Variation	[7]
Depression	DIS3XJ69	Strong	Biomarker	[8]
Disseminated intravascular coagulation	DISCAVOZ	Strong	Biomarker	[9]
Epilepsy with generalized tonic-clonic seizures	DISMG0FL	Strong	Biomarker	[10]
Hypotension	DISYNSM9	Strong	Biomarker	[11]
Irritable bowel syndrome	DIS27206	Strong	Genetic Variation	[12]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[13]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[14]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[15]
Prostate disease	DISFVG19	Strong	Biomarker	[16]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[17]
Gastric ulcer	DISBBGVO	moderate	Biomarker	[18]
Mood disorder	DISLVMWO	moderate	Biomarker	[19]
High blood pressure	DISY2OHH	Disputed	Biomarker	[20]
Breast cancer	DIS7DPX1	Limited	Biomarker	[21]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[21]
Carcinoma	DISH9F1N	Limited	Therapeutic	[22]
Colon cancer	DISVC52G	Limited	Therapeutic	[22]
Colonic neoplasm	DISSZ04P	Limited	Therapeutic	[22]
Conduct disorder	DISOLUZ1	Limited	Genetic Variation	[23]
Ischemia	DIS5XOOY	Limited	Biomarker	[24]
Undifferentiated carcinoma	DISIAZST	Limited	Therapeutic	[22]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Clozapine	DMFC71L	Approved	Oxytocin-neurophysin 1 (OXT) affects the response to substance of Clozapine.	[28]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydrocortisone	DMGEMB7	Approved	Oxytocin-neurophysin 1 (OXT) affects the abundance of Hydrocortisone.	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Oxytocin-neurophysin 1 (OXT).	[25]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Oxytocin-neurophysin 1 (OXT).	[26]

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-neurophysin 1 (OXT).	[27]

References

• [1] COA-Cl (2-Cl-C.OXT-A) can promote coronary collateral development following acute myocardial infarction in mice.Sci Rep. 2019 Feb 22;9(1):2533. doi: 10.1038/s41598-019-39222-1.
• [2] Oxytocin Genotype Moderates the Impact of Social Support on Psychiatric Distress in Alcohol-Dependent Patients.Alcohol Alcohol. 2018 Jan 1;53(1):57-63. doi: 10.1093/alcalc/agx077.
• [3] Hypothalamic vasopressin and oxytocin mRNA expression in relation to depressive state in Alzheimer's disease: a difference with major depressive disorder.J Neuroendocrinol. 2009 Aug;21(8):722-9. doi: 10.1111/j.1365-2826.2009.01890.x. Epub 2009 Jun 4.
• [4] Evidence that oxytocin exerts anxiolytic effects via oxytocin receptor expressed in serotonergic neurons in mice.J Neurosci. 2009 Feb 18;29(7):2259-71. doi: 10.1523/JNEUROSCI.5593-08.2009.
• [5] Systematic Review of Literature on Single-Nucleotide Polymorphisms Within the Oxytocin and Vasopressin Receptor Genes in the Development of Social Cognition Dysfunctions in Individuals Suffering From Autism Spectrum Disorder.Front Psychiatry. 2019 May 31;10:380. doi: 10.3389/fpsyt.2019.00380. eCollection 2019.
• [6] Effect of age and autism spectrum disorder on oxytocin receptor density in the human basal forebrain and midbrain.Transl Psychiatry. 2018 Dec 4;8(1):257. doi: 10.1038/s41398-018-0315-3.
• [7] Alzheimer's disease-associated (hydroxy)methylomic changes in the brain and blood.Clin Epigenetics. 2019 Nov 27;11(1):164. doi: 10.1186/s13148-019-0755-5.
• [8] Making room for oxytocin in understanding depression.Neurosci Biobehav Rev. 2014 Sep;45:305-22. doi: 10.1016/j.neubiorev.2014.07.005. Epub 2014 Jul 12.
• [9] Labor induction with dinoprostone or oxytocine and postpartum disseminated intravascular coagulation: a hospital-based case-control study.Am J Obstet Gynecol. 2004 Nov;191(5):1637-43. doi: 10.1016/j.ajog.2004.03.021.
• [10] Prostaglandin-oxytocin induction of mid-trimester abortion complicated by grand mal-like seizures.Acta Obstet Gynecol Scand. 1983;62(1):79-81. doi: 10.3109/00016348309155765.
• [11] Oxytocin antagonist disrupts hypotension-evoked renin secretion and other responses in conscious rats.Am J Physiol Regul Integr Comp Physiol. 2001 Mar;280(3):R760-5. doi: 10.1152/ajpregu.2001.280.3.R760.
• [12] Polymorphism in the oxytocin promoter region in patients with lactase non-persistence is not related to symptoms.BMC Gastroenterol. 2009 Nov 30;9:90. doi: 10.1186/1471-230X-9-90.
• [13] Variant in oxytocin receptor gene is associated with amygdala volume.Psychoneuroendocrinology. 2011 Jul;36(6):891-7. doi: 10.1016/j.psyneuen.2010.12.004. Epub 2011 Jan 3.
• [14] Direct Involvement of Androgen Receptor in Oxytocin Gene Expression: Possible Relevance for Mood Disorders.Neuropsychopharmacology. 2017 Sep;42(10):2064-2071. doi: 10.1038/npp.2017.76. Epub 2017 Apr 27.
• [15] Opposite effects of oxytocin on proliferation of osteosarcoma cell lines.Regul Pept. 2008 Oct 9;150(1-3):50-4. doi: 10.1016/j.regpep.2008.02.007. Epub 2008 Mar 4.
• [16] The effect of oxytocin on cell proliferation in the human prostate is modulated by gonadal steroids: implications for benign prostatic hyperplasia and carcinoma of the prostate.Prostate. 2007 Jul 1;67(10):1132-42. doi: 10.1002/pros.20612.
• [17] Decreased Serum Oxytocin and Increased Homocysteine in First-Episode Schizophrenia Patients.Front Psychiatry. 2019 Apr 10;10:217. doi: 10.3389/fpsyt.2019.00217. eCollection 2019.
• [18] Gastric antisecretory and antiulcer activity of oxytocin in rats and guinea pigs.Life Sci. 2001 Nov 21;70(1):17-24. doi: 10.1016/s0024-3205(01)01376-5.
• [19] No association between oxytocin or prolactin gene variants and childhood-onset mood disorders.Psychoneuroendocrinology. 2010 Oct;35(9):1422-8. doi: 10.1016/j.psyneuen.2010.04.008. Epub 2010 May 23.
• [20] Postnatal oxytocin treatment of spontaneously hypertensive male rats decreases blood pressure and body weight in adulthood.Neurosci Lett. 2008 Aug 1;440(2):166-9. doi: 10.1016/j.neulet.2008.05.091. Epub 2008 Jun 16.
• [21] Phosphosulindac (OXT-328) selectively targets breast cancer stem cells in vitro and in human breast cancer xenografts.Stem Cells. 2012 Oct;30(10):2065-75. doi: 10.1002/stem.1139.
• [22] Oxytocin and oxytocin-analogue F314 inhibit cell proliferation and tumor growth of rat and mouse mammary carcinomas.Int J Cancer. 1996 Jun 11;66(6):817-20. doi: 10.1002/(SICI)1097-0215(19960611)66:6<817::AID-IJC18>3.0.CO;2-#.
• [23] Variation in the Oxytocin Receptor Gene Is Associated With Social Cognition and ADHD.J Atten Disord. 2019 May;23(7):702-711. doi: 10.1177/1087054717706757. Epub 2017 May 6.
• [24] Oxytocin and vasopressin constrict rat isolated uterine resistance arteries by activating vasopressin V1A receptors.Eur J Pharmacol. 1999 Jul 2;376(1-2):45-51. doi: 10.1016/s0014-2999(99)00351-9.
• [25] 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.
• [26] Relation of oxytocin to psychological stress responses and hypothalamic-pituitary-adrenocortical axis activity in older women. Psychosom Med. 2006 Mar-Apr;68(2):238-45. doi: 10.1097/01.psy.0000203242.95990.74.
• [27] 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.
• [28] Schizophrenia severity and clozapine treatment outcome association with oxytocinergic genes. Int J Neuropsychopharmacol. 2010 Jul;13(6):793-8. doi: 10.1017/S1461145710000167. Epub 2010 Mar 3.
• [29] Relation of oxytocin to psychological stress responses and hypothalamic-pituitary-adrenocortical axis activity in older women. Psychosom Med. 2006 Mar-Apr;68(2):238-45. doi: 10.1097/01.psy.0000203242.95990.74.