Target Information

Target General Infomation
Target ID
T84486
Former ID
TTDS00264
Target Name
Oxytocin receptor
Gene Name
OXTR
Synonyms
OT-R; OXTR
Target Type
Successful
Disease Androgen decline [ICD10: E20-E35]
Autism [ICD9: 299; ICD10: F84.0]
Erectile dysfunction [ICD9: 302.72, 607.84; ICD10: F52.2, N48.4]
Female sexual dysfunction [ICD9: 302.7; ICD10: F52]
Miscarriage [ICD10: O03]
Premature ejaculation [ICD9: 302.75; ICD10: F52.4]
Postpartum haemorrhage [ICD9: 666; ICD10: O72]
Threatened pre-term labour [ICD10: O60.1, P07.3]
Function
Receptor for oxytocin. The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol- calcium second messenger system.
BioChemical Class
GPCR rhodopsin
Target Validation
T84486
UniProt ID
P30559
Sequence
MEGALAANWSAEAANASAAPPGAEGNRTAGPPRRNEALARVEVAVLCLILLLALSGNACV
LLALRTTRQKHSRLFFFMKHLSIADLVVAVFQVLPQLLWDITFRFYGPDLLCRLVKYLQV
VGMFASTYLLLLMSLDRCLAICQPLRSLRRRTDRLAVLATWLGCLVASAPQVHIFSLREV
ADGVFDCWAVFIQPWGPKAYITWITLAVYIVPVIVLAACYGLISFKIWQNLRLKTAAAAA
AEAPEGAAAGDGGRVALARVSSVKLISKAKIRTVKMTFIIVLAFIVCWTPFFFVQMWSVW
DANAPKEASAFIIVMLLASLNSCCNPWIYMLFTGHLFHELVQRFLCCSASYLKGRRLGET
SASKKSNSSSFVLSHRSSSQRSCSQPSTA
Drugs and Mode of Action
Drug(s) Carbetocin Drug Info Approved Postpartum haemorrhage [1]
Oxytocin Drug Info Approved Autism [2]
ATOSIBAN Drug Info Phase 4 Discovery agent [3], [4]
GSK221149 Drug Info Phase 3 Threatened pre-term labour [5]
Retosiban Drug Info Phase 3 Threatened pre-term labour [6], [7]
Barusiban Drug Info Phase 2 Androgen decline [8]
FE-202767 Drug Info Phase 2 Erectile dysfunction [9]
GSK-557296 Drug Info Phase 2 Premature ejaculation [10]
L-368899 Drug Info Discontinued in Phase 1 Miscarriage [11], [12]
PF-3274167 Drug Info Discontinued in Phase 1 Female sexual dysfunction [13]
TT-235 Drug Info Discontinued in Phase 1 Miscarriage [14]
AS-602305 Drug Info Terminated Androgen decline [15]
L-371257 Drug Info Terminated Discovery agent [16], [17]
Inhibitor 1'-tosylspiro[indene-1,4'-piperidine] Drug Info [18]
ARGENINE VASOPRESSIN Drug Info [19]
ATOSIBAN Drug Info [20]
D(CH2)5[Tyr(Me)2,Thr4,Orn8(5/6C-Flu),Tyr-NH29]VT Drug Info [21]
D(CH2)5[Tyr(Me)2,Thr4,Orn8,Tyr9-NH2]VT Drug Info [21]
DesGly-NH2,d(CH2)5[D-Tyr2,Thr4,Orn8(5/6C-Flu)]VT Drug Info [21]
D[Arg4,Dab8]VP Drug Info [19]
D[Arg4,Lys8]VP Drug Info [19]
D[Arg4,Orn8]VP Drug Info [19]
D[Arg4]AVP Drug Info [19]
D[Cha4,Dab8]VP Drug Info [19]
D[Cha4,Dap8]VP Drug Info [19]
D[Cha4,Lys8]VP Drug Info [19]
D[Cha4,Orn8]VP Drug Info [19]
D[Cha4]AVP Drug Info [19]
D[Leu4,Dab8]VP Drug Info [19]
D[Leu4,Dap8]VP Drug Info [19]
D[Leu4,Lys8]VP Drug Info [19]
D[Leu4,Orn8]VP Drug Info [19]
D[Leu4]AVP Drug Info [19]
D[Lys8(5/6-Flu)]VT Drug Info [21]
D[Orn4,Lys8]VP Drug Info [19]
D[Orn4,Orn8]VP Drug Info [19]
D[Orn4]AVP Drug Info [19]
D[Orn8(5/6C-Flu)]VT Drug Info [21]
D[Thr4,Lys8(5/6C-Flu)]VT Drug Info [21]
D[Thr4,Orn8(5/6C-Flu)]VT Drug Info [21]
D[Val4]AVP Drug Info [19]
L-371257 Drug Info [18]
L-372662 Drug Info [18]
PF-3274167 Drug Info [18]
SR-149415 Drug Info [22]
[Aib7]OT Drug Info [23]
[D-Tic7]OT Drug Info [23]
[Gly(But)7]OT Drug Info [23]
[HO1][Lys8(5/6C-Flu)]VT Drug Info [21]
[HO1][Orn8(5/6C-Flu)]VT Drug Info [21]
[HO1][Orn8(5/6C-Rhm)]VT Drug Info [21]
[HO1][Thr4,Lys8(5/6C-Flu)]VT Drug Info [21]
[HO1][Thr4,Orn8(5/6C-Flu)]VT Drug Info [21]
[L-Tic7]OT Drug Info [23]
[Lys8(Alexa 488) ]PVA Drug Info [24]
[Lys8(Alexa 546) ]PVA Drug Info [24]
[Mpa1, D-Tic2, Aib7]OT Drug Info [23]
[Mpa1, D-Tic7]OT Drug Info [23]
[Mpa1, D-Tyr(Et)2, Aib7, D-Tic9]OT Drug Info [23]
[Mpa1, D-Tyr(Et)2, Aib7]OT Drug Info [23]
[Mpa1, D-Tyr(Et)2, D-Tic7, Aib9]OT Drug Info [23]
[Mpa1, D-Tyr(Et)2, D-Tic7, D-Tic9]OT Drug Info [23]
[Mpa1, D-Tyr(Et)2, D-Tic7]OT Drug Info [23]
[Mpa1, D-Tyr(Et)2, Gly(But)3, Gly(But)7]OT Drug Info [23]
[Mpa1, D-Tyr(Et)2, Gly(But)7]OT Drug Info [23]
[Mpa1, D-Tyr(Et)2, L-Tic7]OT Drug Info [23]
[Mpa1, D-Tyr(Et)2, Pip7]OT Drug Info [23]
[Mpa1, L-Tic7]OT Drug Info [23]
[Pip7]OT Drug Info [23]
Antagonist AS-602305 Drug Info [25]
Barusiban Drug Info [26]
compound 37 Drug Info [27]
d(CH2)5[Tyr(Me)2]AVP Drug Info [28]
GSK-557296 Drug Info [29]
GSK221149 Drug Info [30]
L-365,209 Drug Info [28]
L-366,509 Drug Info [28]
L-366,682 Drug Info [28]
L-366,948 Drug Info [28]
L-367,773 Drug Info [28]
L-368899 Drug Info [31]
L023103 Drug Info [32]
LS-192629 Drug Info [33]
PF-271836 Drug Info [34]
SSR126768A Drug Info [35]
TT-235 Drug Info [36], [37]
[35S]-non-peptide OT antagonist Drug Info [38]
Agonist Carbetocin Drug Info [39], [40], [41]
dAVP Drug Info [42]
FE-202767 Drug Info [34]
[3H]OT (human, mouse, rat) Drug Info [43]
[Phe3]OT Drug Info [44]
[Thr4,Gly7]OT Drug Info [45]
Modulator Oxytocin Drug Info [34]
Retosiban Drug Info
Pathways
KEGG Pathway Calcium signaling pathway
cAMP signaling pathway
Neuroactive ligand-receptor interaction
Oxytocin signaling pathway
NetPath Pathway TGF_beta_Receptor Signaling Pathway
PANTHER Pathway Oxytocin receptor mediated signaling pathway
Reactome Vasopressin-like receptors
G alpha (q) signalling events
WikiPathways GPCRs, Class A Rhodopsin-like
Myometrial Relaxation and Contraction Pathways
Oxytocin signaling
Gastrin-CREB signalling pathway via PKC and MAPK
Peptide GPCRs
GPCR ligand binding
GPCR downstream signaling
References
REF 1Clinical Textbook of Dental Hygiene and Therapy. 2006, P237. By Robert Ireland.
REF 2(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2174).
REF 3ClinicalTrials.gov (NCT01673399) Oxytocin Antagonist in Patients With Repeated Failure of Implantation. U.S. National Institutes of Health.
REF 4(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2213).
REF 5Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800023904)
REF 6ClinicalTrials.gov (NCT02377466) A Phase III Efficacy and Safety Study of Intravenous Retosiban Versus Placebo for Women in Spontaneous Preterm Labor. U.S. National Institutes of Health.
REF 7(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8403).
REF 8ClinicalTrials.gov (NCT00209326) A Proof of Concept Study Assessing the Effect of Four Different Single Bolus Intravenous Doses of FE200440 and Placebo on Stopping Preterm Labor. U.S. National Institutes of Health.
REF 9ClinicalTrials.gov (NCT02545127) Trial Exploring the Efficacy and Safety of FE 202767.
REF 10ClinicalTrials.gov (NCT01021553) A Study To Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Two Oral Doses of GSK557296 in a Study in Men With Premature Ejaculation. U.S. National Institutes of Health.
REF 11(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2249).
REF 12Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010521)
REF 13Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025596)
REF 14Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010692)
REF 15Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020775)
REF 16(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2252).
REF 17Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008273)
REF 18J Med Chem. 2010 Sep 23;53(18):6525-38.Oral oxytocin antagonists.
REF 19J Med Chem. 2007 Feb 22;50(4):835-47.Design and synthesis of the first selective agonists for the rat vasopressin V(1b) receptor: based on modifications of deamino-[Cys1]arginine vasopressin at positions 4 and 8.
REF 20Bioorg Med Chem Lett. 2006 Feb 15;16(4):954-9. Epub 2005 Nov 15.Pyridobenzodiazepines: a novel class of orally active, vasopressin V2 receptor selective agonists.
REF 21J Med Chem. 2002 Jun 6;45(12):2579-88.Synthesis and characterization of fluorescent antagonists and agonists for human oxytocin and vasopressin V(1)(a) receptors.
REF 22Bioorg Med Chem Lett. 2009 Nov 1;19(21):6018-22. Epub 2009 Sep 17.Tetrahydroquinoline sulfonamides as vasopressin 1b receptor antagonists.
REF 23Eur J Med Chem. 2007 Jun;42(6):799-806. Epub 2007 Jan 10.Synthesis and biological activity of oxytocin analogues containing conformationally-restricted residues in position 7.
REF 24J Med Chem. 2007 Oct 4;50(20):4976-85. Epub 2007 Sep 12.Toward efficient drug screening by homogeneous assays based on the development of new fluorescent vasopressin and oxytocin receptor ligands.
REF 25Clinical pipeline report, company report or official report of darkpharma.
REF 26The effect of barusiban, a selective oxytocin antagonist, in threatened preterm labor at late gestational age: a randomized, double-blind, placebo-controlled trial. Am J Obstet Gynecol. 2009 Jun;200(6):627.e1-10.
REF 272,5-diketopiperazines as potent, selective, and orally bioavailable oxytocin antagonists. 2. Synthesis, chirality, and pharmacokinetics. J Med Chem. 2005 Nov 3;48(22):6956-69.
REF 28Characterization of the human oxytocin receptor stably expressed in 293 human embryonic kidney cells. Life Sci. 1995;57(24):2253-61.
REF 29Inhibition of ejaculation by the non-peptide oxytocin receptor antagonist GSK557296: a multi-level site of action. Br J Pharmacol. 2013 Aug;169(7):1477-85.
REF 30Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
REF 31Pharmacokinetics and disposition of the oxytocin receptor antagonist L-368,899 in rats and dogs. Drug Metab Dispos. 1997 Oct;25(10):1113-8.
REF 32Discovery and development of a new class of potent, selective, orally active oxytocin receptor antagonists. J Med Chem. 2005 Dec 1;48(24):7882-905.
REF 33Pharmacology of (2S,4Z)-N-[(2S)-2-hydroxy-2-phenylethyl]-4-(methoxyimino) -1-[(2'-methyl[1,1'-biphenyl]-4-yl)carbonyl]-2-pyrrolidinecarboxamide, a new potent and selective nonpeptide antagonist of the oxytocin receptor. J Pharmacol Exp Ther. 2003 Jul;306(1):253-61. Epub 2003 Mar 26.
REF 34(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 369).
REF 35SSR126768A (4-chloro-3-[(3R)-(+)-5-chloro-1-(2,4-dimethoxybenzyl)-3-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl]-N-ethyl-N-(3-pyridylmethyl)-benzamide, hydrochloride): a new selective and orally active oxytocin receptor antagonist for the prevention of preterm labor. J Pharmacol Exp Ther. 2004 Apr;309(1):414-24. Epub 2004 Jan 13.
REF 36In vivo activity of the potent oxytocin antagonist on uterine activity in the rat. In Vivo. 2004 Nov-Dec;18(6):763-6.
REF 37Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
REF 38A nonpeptide oxytocin receptor antagonist radioligand highly selective for human receptors. Eur J Pharmacol. 2002 Aug 16;450(1):19-28.
REF 39Structure and expression of a human oxytocin receptor. Nature. 1992 Apr 9;356(6369):526-9.
REF 40Peptide and non-peptide agonists and antagonists for the vasopressin and oxytocin V1a, V1b, V2 and OT receptors: research tools and potential therapeutic agents. Prog Brain Res. 2008;170:473-512.
REF 41Structural organization of the human oxytocin receptor gene. J Biol Chem. 1994 Dec 23;269(51):32451-6.
REF 42Design of potent and selective agonists for the human vasopressin V1b receptor based on modifications of [deamino-cys1]arginine vasopressin at position 4. J Med Chem. 2004 Apr 22;47(9):2375-88.
REF 43Oxytocin receptors and human parturition: a dual role for oxytocin in the initiation of labor. Science. 1982 Mar 12;215(4538):1396-8.
REF 44Two aromatic residues regulate the response of the human oxytocin receptor to the partial agonist arginine vasopressin. FEBS Lett. 1996 Nov 18;397(2-3):201-6.
REF 45[3H]-[Thr4,Gly7]OT: a highly selective ligand for central and peripheral OT receptors. Am J Physiol. 1988 Jan;254(1 Pt 1):E31-8.

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