Target Information

Target General Information

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Target ID

T84486 (Former ID: TTDS00264)

Target Name

Oxytocin receptor (OTR)

Synonyms

OT-R

Gene Name

OXTR

Target Type

Successful target

[1]

Disease

[+] 3 Target-related Diseases

Acute diabete complication [ICD-11: 5A2Y]

Autism spectrum disorder [ICD-11: 6A02]

Postpartum haemorrhage [ICD-11: JA43]

Function

The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system. Receptor for oxytocin.

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BioChemical Class

GPCR rhodopsin

UniProt ID

OXYR_HUMAN

Sequence

MEGALAANWSAEAANASAAPPGAEGNRTAGPPRRNEALARVEVAVLCLILLLALSGNACV
LLALRTTRQKHSRLFFFMKHLSIADLVVAVFQVLPQLLWDITFRFYGPDLLCRLVKYLQV
VGMFASTYLLLLMSLDRCLAICQPLRSLRRRTDRLAVLATWLGCLVASAPQVHIFSLREV
ADGVFDCWAVFIQPWGPKAYITWITLAVYIVPVIVLAACYGLISFKIWQNLRLKTAAAAA
AEAPEGAAAGDGGRVALARVSSVKLISKAKIRTVKMTFIIVLAFIVCWTPFFFVQMWSVW
DANAPKEASAFIIVMLLASLNSCCNPWIYMLFTGHLFHELVQRFLCCSASYLKGRRLGET
SASKKSNSSSFVLSHRSSSQRSCSQPSTA

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3D Structure

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PDB

ADReCS ID

BADD_A01759 ; BADD_A05900

HIT2.0 ID

T76GZS

Drugs and Modes of Action

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Approved Drug(s)

[+] 3 Approved Drugs

Carbetocin

Drug Info

Approved

Postpartum haemorrhage

[2]

Desmopressin

Drug Info

Approved

Diabetic complication

[3], [4], [5]

Oxytocin

Drug Info

Approved

Autism spectrum disorder

[6]

Clinical Trial Drug(s)

[+] 5 Clinical Trial Drugs

Retosiban

Drug Info

Phase 3

Preterm labour

[7], [8]

Barusiban

Drug Info

Phase 2

Androgen deficiency

[9]

FE-202767

Drug Info

Phase 2

Erectile dysfunction

[10]

GSK-557296

Drug Info

Phase 2

Premature ejaculation

[11]

SSR149415

Drug Info

Phase 2

Anxiety disorder

[12], [13], [14]

Discontinued Drug(s)

[+] 4 Discontinued Drugs

L-368899

Drug Info

Discontinued in Phase 1

Miscarriage

[15], [16]

PF-3274167

Drug Info

Discontinued in Phase 1

Female sexual arousal dysfunction

[17]

TT-235

Drug Info

Discontinued in Phase 1

Miscarriage

[18]

AS-602305

Drug Info

Terminated

Androgen deficiency

[19]

Mode of Action

[+] 4 Modes of Action

Agonist

[+] 5 Agonist drugs

Carbetocin

Drug Info

[1], [20], [21]

Desmopressin

Drug Info

[22]

FE-202767

Drug Info

[23]

[Phe3]OT

Drug Info

[45]

[Thr4,Gly7]OT

Drug Info

[46]

Modulator

[+] 2 Modulator drugs

Oxytocin

Drug Info

[23], [24]

Retosiban

Drug Info

[26]

Inhibitor

[+] 56 Inhibitor drugs

ATOSIBAN

Drug Info

[25]

SSR149415

Drug Info

[29]

PF-3274167

Drug Info

[32]

L-371257

Drug Info

[32]

1'-tosylspiro[indene-1,4'-piperidine]

Drug Info

[32]

ARGENINE VASOPRESSIN

Drug Info

[35]

D(CH2)5[Tyr(Me)2,Thr4,Orn8(5/6C-Flu),Tyr-NH29]VT

Drug Info

[36]

D(CH2)5[Tyr(Me)2,Thr4,Orn8,Tyr9-NH2]VT

Drug Info

[36]

DesGly-NH2,d(CH2)5[D-Tyr2,Thr4,Orn8(5/6C-Flu)]VT

Drug Info

[36]

D[Arg4,Dab8]VP

Drug Info

[35]

D[Arg4,Lys8]VP

Drug Info

[35]

D[Arg4,Orn8]VP

Drug Info

[35]

D[Arg4]AVP

Drug Info

[35]

D[Cha4,Dab8]VP

Drug Info

[35]

D[Cha4,Dap8]VP

Drug Info

[35]

D[Cha4,Lys8]VP

Drug Info

[35]

D[Cha4,Orn8]VP

Drug Info

[35]

D[Cha4]AVP

Drug Info

[35]

D[Leu4,Dab8]VP

Drug Info

[35]

D[Leu4,Dap8]VP

Drug Info

[35]

D[Leu4,Lys8]VP

Drug Info

[35]

D[Leu4,Orn8]VP

Drug Info

[35]

D[Leu4]AVP

Drug Info

[35]

D[Lys8(5/6-Flu)]VT

Drug Info

[36]

D[Orn4,Lys8]VP

Drug Info

[35]

D[Orn4,Orn8]VP

Drug Info

[35]

D[Orn4]AVP

Drug Info

[35]

D[Orn8(5/6C-Flu)]VT

Drug Info

[36]

D[Thr4,Lys8(5/6C-Flu)]VT

Drug Info

[36]

D[Thr4,Orn8(5/6C-Flu)]VT

Drug Info

[36]

D[Val4]AVP

Drug Info

[35]

L-372662

Drug Info

[32]

[Aib7]OT

Drug Info

[43]

[D-Tic7]OT

Drug Info

[43]

[Gly(But)7]OT

Drug Info

[43]

[HO1][Lys8(5/6C-Flu)]VT

Drug Info

[36]

[HO1][Orn8(5/6C-Flu)]VT

Drug Info

[36]

[HO1][Orn8(5/6C-Rhm)]VT

Drug Info

[36]

[HO1][Thr4,Lys8(5/6C-Flu)]VT

Drug Info

[36]

[HO1][Thr4,Orn8(5/6C-Flu)]VT

Drug Info

[36]

[L-Tic7]OT

Drug Info

[43]

[Lys8(Alexa 488) ]PVA

Drug Info

[44]

[Lys8(Alexa 546) ]PVA

Drug Info

[44]

[Mpa1, D-Tic2, Aib7]OT

Drug Info

[43]

[Mpa1, D-Tic7]OT

Drug Info

[43]

[Mpa1, D-Tyr(Et)2, Aib7, D-Tic9]OT

Drug Info

[43]

[Mpa1, D-Tyr(Et)2, Aib7]OT

Drug Info

[43]

[Mpa1, D-Tyr(Et)2, D-Tic7, Aib9]OT

Drug Info

[43]

[Mpa1, D-Tyr(Et)2, D-Tic7, D-Tic9]OT

Drug Info

[43]

[Mpa1, D-Tyr(Et)2, D-Tic7]OT

Drug Info

[43]

[Mpa1, D-Tyr(Et)2, Gly(But)3, Gly(But)7]OT

Drug Info

[43]

[Mpa1, D-Tyr(Et)2, Gly(But)7]OT

Drug Info

[43]

[Mpa1, D-Tyr(Et)2, L-Tic7]OT

Drug Info

[43]

[Mpa1, D-Tyr(Et)2, Pip7]OT

Drug Info

[43]

[Mpa1, L-Tic7]OT

Drug Info

[43]

[Pip7]OT

Drug Info

[43]

Antagonist

[+] 27 Antagonist drugs

Barusiban

Drug Info

[27]

GSK-557296

Drug Info

[28]

PMID28906174-Compound-figure1g

Drug Info

[30]

Pyrrolidine derivative 10

Drug Info

[30]

Pyrrolidine derivative 11

Drug Info

[30]

Pyrrolidine derivative 12

Drug Info

[30]

Pyrrolidine derivative 13

Drug Info

[30]

Pyrrolidine derivative 9

Drug Info

[30]

Triazole derivative 4

Drug Info

[30]

Triazole derivative 5

Drug Info

[30]

Triazole derivative 6

Drug Info

[30]

Triazole derivative 7

Drug Info

[30]

L-368899

Drug Info

[31]

TT-235

Drug Info

[33], [4]

AS-602305

Drug Info

[34]

d(CH2)5[Tyr(Me)2]AVP

Drug Info

[37]

L-365,209

Drug Info

[37]

L-366,509

Drug Info

[37]

L-366,682

Drug Info

[37]

L-366,948

Drug Info

[37]

L-367,773

Drug Info

[37]

L023103

Drug Info

[38]

LS-192629

Drug Info

[39]

PF-271836

Drug Info

[23]

PMID16250654C37

Drug Info

[40]

SSR126768A

Drug Info

[41]

[35S]-non-peptide OT antagonist

Drug Info

[42]

Chemical Structure based Activity Landscape of Target

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Drug Property Profile of Target

Top

(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Co-Targets

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Co-Targets

Co-Targets Info

Target Poor or Non Binders

Top

Target Poor or Non Binders

Target Poor or Non Binders Info

Target Regulators

Top

Target-regulating microRNAs

Target-regulating microRNAs Info

Target Affiliated Biological Pathways

Top

KEGG Pathway

[+] 4 KEGG Pathways

Calcium signaling pathway

cAMP signaling pathway

Neuroactive ligand-receptor interaction

Oxytocin signaling pathway

NetPath Pathway

[+] 1 NetPath Pathways

TGF_beta_Receptor Signaling Pathway

Panther Pathway

[+] 1 Panther Pathways

Oxytocin receptor mediated signaling pathway

Reactome

[+] 2 Reactome Pathways

Vasopressin-like receptors

G alpha (q) signalling events

WikiPathways

[+] 7 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

Target-Related Models and Studies

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Target Validation

Target Validation Info

References

Top

REF 1

Peptide 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 2

Clinical Textbook of Dental Hygiene and Therapy. 2006, P237. By Robert Ireland.

REF 3

URL: 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: 2182).

REF 4

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015

REF 5

ClinicalTrials.gov (NCT00748072) 1-deamino 8-d-arginine Vasopressin (DDAVP) in Percutaneous Ultrasound-guided Renal Biopsy. U.S. National Institutes of Health.

REF 6

REF 7

REF 8

ClinicalTrials.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 9

ClinicalTrials.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 10

ClinicalTrials.gov (NCT02545127) Trial Exploring the Efficacy and Safety of FE 202767.

REF 11

ClinicalTrials.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 12

REF 13

Anxiolytic- and antidepressant-like effects of the non-peptide vasopressin V1b receptor antagonist, SSR149415, suggest an innovative approach for t... Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):6370-5.

REF 14

Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008 Aug;33(9):2080-92.

REF 15

REF 16

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010521)

REF 17

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025596)

REF 18

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010692)

REF 19

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020775)

REF 20

Structural organization of the human oxytocin receptor gene. J Biol Chem. 1994 Dec 23;269(51):32451-6.

REF 21

Structure and expression of a human oxytocin receptor. Nature. 1992 Apr 9;356(6369):526-9.

REF 22

Design 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 23

REF 24

Oxytocin receptors and human parturition: a dual role for oxytocin in the initiation of labor. Science. 1982 Mar 12;215(4538):1396-8.

REF 25

Pyridobenzodiazepines: a novel class of orally active, vasopressin V2 receptor selective agonists. Bioorg Med Chem Lett. 2006 Feb 15;16(4):954-9.

REF 26

The Effect of an Oxytocin Receptor Antagonist (Retosiban, GSK221149A) on the Response of Human Myometrial Explants to Prolonged Mechanical Stretch.Endocrinology.2015 Oct;156(10):3511-6.

REF 27

The 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 28

Inhibition 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 29

Tetrahydroquinoline sulfonamides as vasopressin 1b receptor antagonists. Bioorg Med Chem Lett. 2009 Nov 1;19(21):6018-22.

REF 30

A patent review of oxytocin receptor antagonists 2013-2017.Expert Opin Ther Pat. 2017 Dec;27(12):1287-1290.

REF 31

Pharmacokinetics and disposition of the oxytocin receptor antagonist L-368,899 in rats and dogs. Drug Metab Dispos. 1997 Oct;25(10):1113-8.

REF 32

Oral oxytocin antagonists. J Med Chem. 2010 Sep 23;53(18):6525-38.

REF 33

In vivo activity of the potent oxytocin antagonist on uterine activity in the rat. In Vivo. 2004 Nov-Dec;18(6):763-6.

REF 34

Clinical pipeline report, company report or official report of darkpharma.

REF 35

Design and synthesis of the first selective agonists for the rat vasopressin V(1b) receptor: based on modifications of deamino-[Cys1]arginine vasop... J Med Chem. 2007 Feb 22;50(4):835-47.

REF 36

Synthesis and characterization of fluorescent antagonists and agonists for human oxytocin and vasopressin V(1)(a) receptors. J Med Chem. 2002 Jun 6;45(12):2579-88.

REF 37

Characterization of the human oxytocin receptor stably expressed in 293 human embryonic kidney cells. Life Sci. 1995;57(24):2253-61.

REF 38

Discovery 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 39

Pharmacology of (2S,4Z)-N-[(2S)-2-hydroxy-2-phenylethyl]-4-(methoxyimino) -1-[(2'-methyl[1,1'-biphenyl]-4-yl)carbonyl]-2-pyrrolidinecarboxamide, a ... J Pharmacol Exp Ther. 2003 Jul;306(1):253-61.

REF 40

2,5-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 41

SSR126768A (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, ... J Pharmacol Exp Ther. 2004 Apr;309(1):414-24.

REF 42

A nonpeptide oxytocin receptor antagonist radioligand highly selective for human receptors. Eur J Pharmacol. 2002 Aug 16;450(1):19-28.

REF 43

Synthesis and biological activity of oxytocin analogues containing conformationally-restricted residues in position 7. Eur J Med Chem. 2007 Jun;42(6):799-806.

REF 44

Toward efficient drug screening by homogeneous assays based on the development of new fluorescent vasopressin and oxytocin receptor ligands. J Med Chem. 2007 Oct 4;50(20):4976-85.

REF 45

Two 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 46

[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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