Target Information

Target General Infomation
Target ID
T66237
Former ID
TTDS00111
Target Name
Vasopressin V2 receptor
Gene Name
AVPR2
Synonyms
AVPR V2; Antidiuretic hormone receptor; Renal-type arginine vasopressin receptor; AVPR2
Target Type
Successful
Disease Acute and chronic heart failure [ICD9: 428; ICD10: I50]
Congestive heart failure [ICD9: 428; ICD10: I50]
Dysmenorrhea [ICD9: 625.3; ICD10: N94.4-N94.6]
Euvolemic hyponatremia; Hypervolemic hyponatremia [ICD9: 276.1; ICD10: E87.1]
Euvolemic hyponatremia [ICD9: 276.1; ICD10: E87.1]
Enuresis; Polyuria; Diabetes insipidus [ICD9: 250, 253.5, 307.6, 588.1, 788.30, 788.42; ICD10: E08-E13, E23.2, F98.0, N25.1]
Hypervolaemic hyponatraemia; Euvolaemic hyponatraemia [ICD9: 276.1; ICD10: E87.1]
Heart failure [ICD9: 428; ICD10: I50]
Hyponatraemia [ICD10: E87.1]
Nocturia [ICD10: R35]
Urinary incontinence [ICD9: 788.3; ICD10: N39.3, N39.4, R32]
Function
Receptor for arginine vasopressin. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Involved in renal water reabsorption.
BioChemical Class
GPCR rhodopsin
Target Validation
T66237
UniProt ID
P30518
Sequence
MLMASTTSAVPGHPSLPSLPSNSSQERPLDTRDPLLARAELALLSIVFVAVALSNGLVLA
ALARRGRRGHWAPIHVFIGHLCLADLAVALFQVLPQLAWKATDRFRGPDALCRAVKYLQM
VGMYASSYMILAMTLDRHRAICRPMLAYRHGSGAHWNRPVLVAWAFSLLLSLPQLFIFAQ
RNVEGGSGVTDCWACFAEPWGRRTYVTWIALMVFVAPTLGIAACQVLIFREIHASLVPGP
SERPGGRRRGRRTGSPGEGAHVSAAVAKTVRMTLVIVVVYVLCWAPFFLVQLWAAWDPEA
PLEGAPFVLLMLLASLNSCTNPWIYASFSSSVSSELRSLLCCARGRTPPSLGPQDESCTT
ASSSLAKDTSS
Drugs and Mode of Action
Drug(s) Conivaptan Drug Info Approved Euvolemic hyponatremia [1], [2]
DDAVP Drug Info Approved Diabetes [3]
Mozavaptan Drug Info Approved Hyponatraemia [4], [5], [6]
OPC-31260 Drug Info Approved Hyponatraemia [5], [6]
Tolvaptan Drug Info Approved Hypervolaemic hyponatraemia; Euvolaemic hyponatraemia [7], [8]
Vasopressin Drug Info Approved Enuresis; Polyuria; Diabetes insipidus [9], [10]
ATOSIBAN Drug Info Phase 4 Discovery agent [11], [12]
Lixivaptan Drug Info Phase 3 Euvolemic hyponatremia; Hypervolemic hyponatremia [13], [14]
Satavaptan Drug Info Phase 3 Acute and chronic heart failure [15], [16]
SR121463B Drug Info Phase 3 Discovery agent [17]
Tolvaptan Drug Info Phase 3 Heart failure [7], [8]
ASP-7035 Drug Info Phase 2 Nocturia [18]
Lixivaptan Drug Info Phase 2 Congestive heart failure [13], [14]
SPD-556 Drug Info Phase 2 Heart failure [19]
VA-106483 Drug Info Phase 2 Nocturia [20]
OPC-51803 Drug Info Discontinued in Phase 1 Urinary incontinence [21], [22]
OX 19 Drug Info Discontinued in Phase 1 Urinary incontinence [23]
VNA-932 Drug Info Discontinued in Phase 1 Urinary incontinence [24], [25]
JTV-605 Drug Info Terminated Dysmenorrhea [26]
Inhibitor ARGENINE VASOPRESSIN Drug Info [27]
ATOSIBAN Drug Info [28]
D(CH2)5[Tyr(Me)2,Thr4,Orn8,Tyr9-NH2]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[Orn4,Lys8]VP Drug Info [27]
D[Orn4,Orn8]VP Drug Info [27]
D[Orn4]AVP Drug Info [27]
D[Val4]AVP Drug Info [27]
L-372662 Drug Info [30]
Mozavaptan Drug Info [31]
SR-149415 Drug Info [32]
VA-106483 Drug Info [33]
YM-35278 Drug Info [34]
Agonist ASP-7035 Drug Info [35]
dAVP Drug Info [36]
DDAVP Drug Info [37], [38], [39], [40]
OPC-51803 Drug Info [41]
OX 19 Drug Info [42]
Vasopressin Drug Info [43]
VNA-932 Drug Info [44], [6]
[3H]OT (human, mouse, rat) Drug Info [45]
[Phe3]OT Drug Info [46]
[Val4]AVP Drug Info [47]
Antagonist CL-385004 Drug Info [48]
d(CH2)5[D-Ile2,Ile4]AVP Drug Info [49]
d(CH2)5[Tyr(Me)2]AVP Drug Info [49]
d[Pen1,Tyr(Me)2]AVP Drug Info [49]
FR161282 Drug Info [48]
JTV-605 Drug Info [48]
Lixivaptan Drug Info [50]
OPC-31260 Drug Info [51], [52], [48]
Satavaptan Drug Info [15]
SPD-556 Drug Info [45]
SR 121463 A Drug Info [51]
SR121463B Drug Info [37]
Tolvaptan Drug Info [7], [53]
VP-343 Drug Info [48]
YM 218 Drug Info [54]
YM 471 Drug Info [55]
[3H]SR 121463A Drug Info [56]
Modulator Conivaptan Drug Info [57], [58]
Pathways
KEGG Pathway Neuroactive ligand-receptor interaction
Vasopressin-regulated water reabsorption
Pathway Interaction Database Arf6 trafficking events
PathWhiz Pathway Vasopressin Regulation of Water Homeostasis
Reactome Vasopressin-like receptors
G alpha (s) signalling events
Vasopressin regulates renal water homeostasis via Aquaporins
WikiPathways GPCRs, Class A Rhodopsin-like
Regulation of Water Balance by Renal Aquaporins
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 3ClinicalTrials.gov (NCT00748072) 1-deamino 8-d-arginine Vasopressin (DDAVP) in Percutaneous Ultrasound-guided Renal Biopsy. 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: 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 7Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
REF 8(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: 2226).
REF 9New topics in vasopressin receptors and approach to novel drugs: research and development of conivaptan hydrochloride (YM087), a drug for the treatment of hyponatremia. J Pharmacol Sci. 2009 Jan;109(1):53-9.
REF 10(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: 2168).
REF 11ClinicalTrials.gov (NCT01673399) Oxytocin Antagonist in Patients With Repeated Failure of Implantation. U.S. National Institutes of Health.
REF 12(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 13Physical state of kappa-carrageenan modulates the mode of action of kappa-carrageenase from Pseudoalteromonas carrageenovora. Biochem J. 2009 May 1;419(3):545-53.
REF 14(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: 2238).
REF 15Post-translational import of protein into the endoplasmic reticulum of a trypanosome: an in vitro system for discovery of anti-trypanosomal chemical entities. Biochem J. 2009 Apr 15;419(2):507-17.
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: 2199).
REF 17ClinicalTrials.gov (NCT00264914) Safety and Efficacy of SR121463B in Patients With Syndrome of Inappropriate Antidiuretic Hormone Secretion. U.S. National Institutes of Health.
REF 18Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800030285)
REF 19ClinicalTrials.gov (NCT01179607) Study of Efficacy of a Vasopressin 2 Receptor Antagonist M0002 for Treatment of Ascites in Cirrhotic Subjects With Hypo- or Normonatraemia. U.S. National Institutes of Health.
REF 20ClinicalTrials.gov (NCT01038843) Efficacy Study of VA106483 in Males With Nocturia.. U.S. National Institutes of Health.
REF 21(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: 2173).
REF 22Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010599)
REF 23Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021110)
REF 24(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: 3537).
REF 25Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800013621)
REF 26Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010443)
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. 2010 Sep 23;53(18):6525-38.Oral oxytocin antagonists.
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 33J Med Chem. 2008 Dec 25;51(24):8124-34.New benzylureas as a novel series of potent, nonpeptidic vasopressin V2 receptor agonists.
REF 34Bioorg Med Chem. 2008 Nov 1;16(21):9524-35. Epub 2008 Sep 17.Preparation of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene)acetamide derivatives as novel arginine vasopressin V(2) receptor agonists.
REF 35Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800030285)
REF 36Design 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 37Vasopressin-induced von Willebrand factor secretion from endothelial cells involves V2 receptors and cAMP. J Clin Invest. 2000 Jul;106(1):107-16.
REF 38Hydronephrosis: prevention by restoration of urinary concentrating ability using desamino-8D-arginine vasopressin (DDAVP) in Brattleboro rats. Int J Exp Pathol. 1991 Oct;72(5):581-7.
REF 39An extracellular residue determines the agonist specificity of V2 vasopressin receptors. FEBS Lett. 1995 Mar 27;362(1):19-23.
REF 40The abnormal quinine drinking aversion in the Brattleboro rat with diabetes insipidus is reversed by the vasopressin agonist DDAVP: a possible role for vasopressin in the motivation to drink. PhysiolBehav. 1994 Mar;55(3):407-12.
REF 41Effects of OPC-51803, a novel, nonpeptide vasopressin V2-receptor agonist, on micturition frequency in Brattleboro and aged rats. J Pharmacol Sci. 2003 Dec;93(4):484-8.
REF 42Investigation of mechanism of desmopressin binding in vasopressin V2 receptor versus vasopressin V1a and oxytocin receptors: molecular dynamics simulation of the agonist-bound state in the membrane-aqueous system. Biopolymers. 2006 Apr 5;81(5):321-38.
REF 43Vasopressin receptors: structure/function relationships and signal transduction in target cells. J Soc Biol. 2005;199(4):351-9.
REF 44Biased Agonist Pharmacochaperones of the AVP V2 Receptor May Treat Congenital Nephrogenic Diabetes Insipidus. J Am Soc Nephrol. 2009 October; 20(10): 2190-2203.
REF 45(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: 368).
REF 46Tyr115 is the key residue for determining agonist selectivity in the V1a vasopressin receptor. EMBO J. 1995 May 15;14(10):2176-82.
REF 47[1-deamino-4-cyclohexylalanine] arginine vasopressin: a potent and specific agonist for vasopressin V1b receptors. Endocrinology. 2002 Dec;143(12):4655-64.
REF 48Nonpeptide vasopressin receptor antagonists: development of selective and orally active V1a, V2 and V1b receptor ligands. Prog Brain Res. 2002;139:197-210.
REF 49Binding properties of a selective tritiated vasopressin V2 receptor antagonist, [H]-SR 121463. Kidney Int. 2000 Oct;58(4):1613-22.
REF 50Emerging drugs for acute and chronic heart failure: current and future developments. Expert Opin Emerg Drugs. 2007 Mar;12(1):75-95.
REF 51Nonpeptide vasopressin antagonists: a new group of hormone blockers entering the scene. Exp Clin Endocrinol Diabetes. 1999;107(3):157-65.
REF 52Effects of an oral vasopressin receptor antagonist (OPC-31260) in a dog with syndrome of inappropriate secretion of antidiuretic hormone. Aust Vet J. 2000 Dec;78(12):825-30.
REF 53Antibody-mediated disruption of the interaction between PCSK9 and the low-density lipoprotein receptor. Biochem J. 2009 May 1;419(3):577-84.
REF 54Effects of YM218, a nonpeptide vasopressin V1A receptor-selective antagonist, on human vasopressin and oxytocin receptors. Pharmacol Res. 2005 Mar;51(3):275-81.
REF 55Effects 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 56Characterization of SR 121463A, a highly potent and selective, orally active vasopressin V2 receptor antagonist. J Clin Invest. 1996 Dec 15;98(12):2729-38.
REF 57Acute 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 58Conivaptan: a dual vasopressin receptor v1a/v2 antagonist [corrected]. Cardiovasc Drug Rev. 2007 Fall;25(3):261-79.

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