Target Information

Target General Infomation
Target ID
T79232
Former ID
TTDS00109
Target Name
Vasopressin V1a receptor
Gene Name
AVPR1A
Synonyms
AVPR V1a; Antidiuretic hormone receptor 1a; V1a vasopressin receptor; V1aR; Vascular/hepatic-type arginine vasopressin receptor; AVPR1A
Target Type
Successful
Disease Anxiety disorder [ICD9: 300, 311; ICD10: F32, F40-F42]
Acute and chronic heart failure [ICD9: 428; ICD10: I50]
Autism [ICD9: 299; ICD10: F84.0]
Cardiotonic [ICD10: I50]
Dysmenorrhea [ICD9: 625.3; ICD10: N94.4-N94.6]
Euvolemic hyponatremia [ICD9: 276.1; ICD10: E87.1]
Female sexual dysfunction [ICD9: 302.7; ICD10: F52]
Hyponatraemia [ICD10: E87.1]
Hypertension [ICD9: 401; ICD10: I10-I16]
Infertility [ICD9: 628; ICD10: N97.0]
Localisation [ICD code not available]
Septic shock [ICD9: 785.52; ICD10: A41.9]
Function
Receptor for arginine vasopressin. The activity of this receptor is mediated by G proteins which activate a phosphatidyl- inositol-calcium second messenger system. Has been involved in social behaviors, including affiliation and attachment.
BioChemical Class
GPCR rhodopsin
Target Validation
T79232
UniProt ID
P37288
Sequence
MRLSAGPDAGPSGNSSPWWPLATGAGNTSREAEALGEGNGPPRDVRNEELAKLEIAVLAV
TFAVAVLGNSSVLLALHRTPRKTSRMHLFIRHLSLADLAVAFFQVLPQMCWDITYRFRGP
DWLCRVVKHLQVFGMFASAYMLVVMTADRYIAVCHPLKTLQQPARRSRLMIAAAWVLSFV
LSTPQYFVFSMIEVNNVTKARDCWATFIQPWGSRAYVTWMTGGIFVAPVVILGTCYGFIC
YNIWCNVRGKTASRQSKGAEQAGVAFQKGFLLAPCVSSVKSISRAKIRTVKMTFVIVTAY
IVCWAPFFIIQMWSVWDPMSVWTESENPTITITALLGSLNSCCNPWIYMFFSGHLLQDCV
QSFPCCQNMKEKFNKEDTDSMSRRQTFYSNNRSPTNSTGMWKDSPKSSKSIKFIPVST
Drugs and Mode of Action
Drug(s) Conivaptan Drug Info Approved Euvolemic hyponatremia [1], [2]
Felypressin Drug Info Approved Localisation [3]
Mozavaptan Drug Info Approved Hyponatraemia [4], [5], [6]
OPC-31260 Drug Info Approved Hyponatraemia [5], [6]
Terlipressin Drug Info Approved Hypertension [7]
ATOSIBAN Drug Info Phase 4 Discovery agent [8], [9]
FE-202158 Drug Info Phase 2 Septic shock [10]
RG7314 Drug Info Phase 2 Autism [11]
VA-111913 Drug Info Phase 2 Dysmenorrhea [12]
SRX-246 Drug Info Phase 1/2 Anxiety disorder [13]
SRX-251 Drug Info Phase 1 Dysmenorrhea [14]
NOX-F37 Drug Info Preclinical Acute and chronic heart failure [15]
OPC-21268 Drug Info Discontinued in Phase 2 Cardiotonic [16], [17]
Relcovaptan Drug Info Discontinued in Phase 2 Discovery agent [18], [19]
PF-3274167 Drug Info Discontinued in Phase 1 Female sexual dysfunction [20]
JTV-605 Drug Info Terminated Dysmenorrhea [21]
L-371257 Drug Info Terminated Discovery agent [22], [23]
Inhibitor 1'-tosylspiro[indene-1,4'-piperidine] Drug Info [24]
A-987306 Drug Info [25]
Ac-Phe-[Orn-Pro-cha-Trp-Arg] Drug Info [26]
ARGENINE VASOPRESSIN Drug Info [27]
ATOSIBAN Drug Info [28]
D(CH2)5[Tyr(Me)2,Thr4,Orn8(5/6C-Flu),Tyr-NH29]VT Drug Info [29]
D(CH2)5[Tyr(Me)2,Thr4,Orn8,Tyr9-NH2]VT Drug Info [29]
DesGly-NH2,d(CH2)5[D-Tyr2,Thr4,Orn8(5/6C-Flu)]VT Drug Info [29]
DVDAVP Drug Info [27]
D[Arg4,Dab8]VP Drug Info [27]
D[Arg4,Lys8]VP Drug Info [27]
D[Arg4,Orn8]VP Drug Info [27]
D[Arg4]AVP Drug Info [27]
D[Cha4,Dab8]VP Drug Info [27]
D[Cha4,Dap8]VP Drug Info [27]
D[Cha4,Lys8]VP Drug Info [27]
D[Cha4,Orn8]VP Drug Info [27]
D[Cha4]AVP Drug Info [27]
D[D-3-Pal2]AVP Drug Info [27]
D[Leu4,Dab8]VP Drug Info [27]
D[Leu4,Dap8]VP Drug Info [27]
D[Leu4,Lys8]VP Drug Info [27]
D[Leu4,Orn8]VP Drug Info [27]
D[Leu4]AVP Drug Info [27]
D[Lys8(5/6-Flu)]VT Drug Info [29]
D[Orn4,Lys8]VP Drug Info [27]
D[Orn4,Orn8]VP Drug Info [27]
D[Orn4]AVP Drug Info [27]
D[Orn8(5/6C-Flu)]VT Drug Info [29]
D[Thr4,Lys8(5/6C-Flu)]VT Drug Info [29]
D[Thr4,Orn8(5/6C-Flu)]VT Drug Info [29]
D[Val4]AVP Drug Info [27]
HO-LVA Drug Info [30]
Hoo-Phe-Orn-Pro-hle-Pff-Phe-NH2 Drug Info [26]
L-371257 Drug Info [24]
L-372662 Drug Info [24]
Mozavaptan Drug Info [31]
PF-3274167 Drug Info [24]
Relcovaptan Drug Info [30]
SR-149415 Drug Info [32]
[HO1][Lys8(5/6C-Flu)]VT Drug Info [29]
[HO1][Orn8(5/6C-Flu)]VT Drug Info [29]
[HO1][Orn8(5/6C-Rhm)]VT Drug Info [29]
[HO1][Thr4,Lys8(5/6C-Flu)]VT Drug Info [29]
[HO1][Thr4,Orn8(5/6C-Flu)]VT Drug Info [29]
[Lys8(Alexa 488) ]PVA Drug Info [30]
[Lys8(Alexa 546) ]PVA Drug Info [30]
Antagonist CL-385004 Drug Info [33]
d(CH2)5[Tyr(Me)2]AVP Drug Info [34]
d[Pen1,Tyr(Me)2]AVP Drug Info [35]
JTV-605 Drug Info [33]
L023103 Drug Info [36]
LS-192629 Drug Info [37]
NOX-F37 Drug Info [15]
OPC-21268 Drug Info [38], [33]
OPC-31260 Drug Info [38]
SRX-246 Drug Info [39]
SRX-251 Drug Info [40]
SSR126768A Drug Info [41]
V1A F/U Drug Info [42]
VA-111913 Drug Info [43]
YM 218 Drug Info [44]
YM 471 Drug Info [45]
[3H]relcovaptan Drug Info [46]
Modulator Conivaptan Drug Info [47], [48]
RG7314 Drug Info [49]
Agonist dAVP Drug Info [50]
FE-202158 Drug Info [51]
Felypressin Drug Info [52]
[3H]OT (human, mouse, rat) Drug Info [53]
[Phe3]OT Drug Info [54]
[Thr4,Gly7]OT Drug Info [53]
[Val4]AVP Drug Info [55]
Stimulator Terlipressin Drug Info [56]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Calcium signaling pathway
Neuroactive ligand-receptor interaction
Vascular smooth muscle contraction
Reactome Vasopressin-like receptors
G alpha (q) signalling events
WikiPathways GPCRs, Class A Rhodopsin-like
Gastrin-CREB signalling pathway via PKC and MAPK
Peptide GPCRs
GPCR ligand binding
GPCR downstream signaling
References
REF 1Emerging diuretics for the treatment of heart failure. Expert Opin Emerg Drugs. 2009 Mar;14(1):195-204.
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: 2203).
REF 3Drug Therapy in Nursing. 2008. By Diane S. Aschenbrenner, Samantha J. Venable.
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: 2197).
REF 5Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001739)
REF 6Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
REF 7Pharmacology, clinical efficacy and safety of terlipressin in esophageal varices bleeding, septic shock and hepatorenal syndrome. Expert Rev Gastroenterol Hepatol. 2007 Dec;1(2):207-17.
REF 8ClinicalTrials.gov (NCT01673399) Oxytocin Antagonist in Patients With Repeated Failure of Implantation. U.S. National Institutes of Health.
REF 9(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 10ClinicalTrials.gov (NCT01612676) Investigating FE 202158 as Potential Primary Treatment in Patients With Early Septic Shock. U.S. National Institutes of Health.
REF 11ClinicalTrials.gov (NCT01793441) A Study of RG7314 to Investigate Efficacy and Safety in Individuals With Autism Spectrum Disorders. U.S. National Institutes of Health.
REF 12ClinicalTrials.gov (NCT00963053) VA111913 Dysmenorrhoea Efficacy and Safety Proof of Concept. U.S. National Institutes of Health.
REF 13Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800023656)
REF 14Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025117)
REF 15Emerging drugs for acute and chronic heart failure: current and future developments. Expert Opin Emerg Drugs. 2007 Mar;12(1):75-95.
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: 2196).
REF 17Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000284)
REF 18(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: 2200).
REF 19Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004942)
REF 20Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025596)
REF 21Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010443)
REF 22(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 23Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008273)
REF 24J Med Chem. 2010 Sep 23;53(18):6525-38.Oral oxytocin antagonists.
REF 25J Med Chem. 2008 Nov 27;51(22):7094-8.cis-4-(Piperazin-1-yl)-5,6,7a,8,9,10,11,11a-octahydrobenzofuro[2,3-h]quinazolin-2-amine (A-987306), a new histamine H4R antagonist that blocks pain responses against carrageenan-induced hyperalgesia.
REF 26Bioorg Med Chem Lett. 2006 Oct 1;16(19):5088-92. Epub 2006 Jul 28.Peptidomimetic C5a receptor antagonists with hydrophobic substitutions at the C-terminus: increased receptor specificity and in vivoactivity.
REF 27J 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 28Bioorg Med Chem Lett. 2008 Jan 1;18(1):90-4. Epub 2007 Nov 6.The discovery of GSK221149A: a potent and selective oxytocin antagonist.
REF 29J 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 30J 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 31J Med Chem. 1981 May;24(5):496-9.New analgesic drugs derived from phencyclidine.
REF 32Bioorg Med Chem Lett. 2009 Nov 1;19(21):6018-22. Epub 2009 Sep 17.Tetrahydroquinoline sulfonamides as vasopressin 1b receptor antagonists.
REF 33Nonpeptide vasopressin receptor antagonists: development of selective and orally active V1a, V2 and V1b receptor ligands. Prog Brain Res. 2002;139:197-210.
REF 34Conserved aromatic residues in the transmembrane region VI of the V1a vasopressin receptor differentiate agonist vs. antagonist ligand binding. Eur J Biochem. 2000 Jul;267(13):4253-63.
REF 35Pharmacological characterization of the human vasopressin receptor subtypes stably expressed in Chinese hamster ovary cells. Br J Pharmacol. 1998 Dec;125(7):1463-70.
REF 36Discovery 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 37Pharmacology 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 38Nonpeptide vasopressin antagonists: a new group of hormone blockers entering the scene. Exp Clin Endocrinol Diabetes. 1999;107(3):157-65.
REF 39Pharmacokinetics and metabolism of SRX246: a potent and selective vasopressin 1a antagonist. J Pharm Sci. 2013 Jun;102(6):2033-43.
REF 40Orally active vasopressin V1a receptor antagonist, SRX251, selectively blocks aggressive behavior. Pharmacol Biochem Behav. 2006 Feb;83(2):169-74. Epub 2006 Feb 28.
REF 41SSR126768A (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 42(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: 366).
REF 43Clinical pipeline report, company report or official report of Avarx.
REF 44Effects of YM218, a nonpeptide vasopressin V1A receptor-selective antagonist, on human vasopressin and oxytocin receptors. Pharmacol Res. 2005 Mar;51(3):275-81.
REF 45Effects of YM471, a nonpeptide AVP V(1A) and V(2) receptor antagonist, on human AVP receptor subtypes expressed in CHO cells and oxytocin receptors in human uterine smooth muscle cells. Br J Pharmacol. 2001 Jul;133(5):746-54.
REF 46Binding of [3H] SR 49059, a potent nonpeptide vasopressin V1a antagonist, to rat and human liver membranes. Biochem Biophys Res Commun. 1994 Feb 28;199(1):353-60.
REF 47Acute hemodynamic effects of conivaptan, a dual V(1A) and V(2) vasopressin receptor antagonist, in patients with advanced heart failure. Circulation. 2001 Nov 13;104(20):2417-23.
REF 48Conivaptan: a dual vasopressin receptor v1a/v2 antagonist [corrected]. Cardiovasc Drug Rev. 2007 Fall;25(3):261-79.
REF 49Social Communication is an Emerging Target for Pharmacotherapy in Autism Spectrum Disorder - A Review of the Literature on Potential Agents. J Can Acad Child Adolesc Psychiatry. 2014 February; 23(1):20-30.
REF 50Design 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 51The selective vasopressin type 1a receptor agonist selepressin (FE 202158) blocks vascular leak in ovine severe sepsis*. Crit Care Med. 2014 Jul;42(7):e525-33.
REF 52Peptide 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 53Mapping peptide-binding domains of the human V1a vasopressin receptor with a photoactivatable linear peptide antagonist. J Biol Chem. 1997 Oct 17;272(42):26536-44.
REF 54Tyr115 is the key residue for determining agonist selectivity in the V1a vasopressin receptor. EMBO J. 1995 May 15;14(10):2176-82.
REF 55[1-deamino-4-cyclohexylalanine] arginine vasopressin: a potent and specific agonist for vasopressin V1b receptors. Endocrinology. 2002 Dec;143(12):4655-64.
REF 56Investigational vasopressin receptor modulators in the pipeline. Expert Opin Investig Drugs. 2009 Aug;18(8):1119-31.

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