Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTK8R02)

• DTT Name: Vasopressin V2 receptor (V2R)
• Synonyms: Renal-type arginine vasopressin receptor; DIR3; DIR; Antidiuretic hormone receptor; AVPR V2; ADHR
• Gene Name: AVPR2
• DTT Type: Successful target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: V2R_HUMAN
• TTD ID: T66237
• Sequence:
  MLMASTTSAVPGHPSLPSLPSNSSQERPLDTRDPLLARAELALLSIVFVAVALSNGLVLA
  ALARRGRRGHWAPIHVFIGHLCLADLAVALFQVLPQLAWKATDRFRGPDALCRAVKYLQM
  VGMYASSYMILAMTLDRHRAICRPMLAYRHGSGAHWNRPVLVAWAFSLLLSLPQLFIFAQ
  RNVEGGSGVTDCWACFAEPWGRRTYVTWIALMVFVAPTLGIAACQVLIFREIHASLVPGP
  SERPGGRRRGRRTGSPGEGAHVSAAVAKTVRMTLVIVVVYVLCWAPFFLVQLWAAWDPEA
  PLEGAPFVLLMLLASLNSCTNPWIYASFSSSVSSELRSLLCCARGRTPPSLGPQDESCTT
  ASSSLAKDTSS
• Function: The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Involved in renal water reabsorption. Receptor for arginine vasopressin.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Vasopressin-regulated water reabsorption (hsa04962)
• Reactome Pathway:
  G alpha (s) signalling events (R-HSA-418555)
  Vasopressin regulates renal water homeostasis via Aquaporins (R-HSA-432040)
  Vasopressin-like receptors (R-HSA-388479)

Molecular Interaction Atlas (MIA) of This DTT

7 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Conivaptan	DM1V329	Euvolemic hyponatremia	5C72	Approved	[2]
Desmopressin	DMS3GVE	Diabetic complication	5A2Y	Approved	[3]
Mozavaptan	DMZ905C	Hyponatraemia	5C72	Approved	[4]
Oxytocin	DMDL27I	Autism spectrum disorder	6A02	Approved	[5]
Tolvaptan	DMIWFRL	Autosomal dominant polycystic kidney disease	GB81	Approved	[6]
Vasopressin	DMQ2FPC	Diabetes insipidus	5A61.5	Approved	[1]
ATOSIBAN	DMB7WYM	N. A.	N. A.	Phase 4	[7]

6 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Lixivaptan	DMDN4ZP	Hyponatraemia	5C72	Phase 3	[8]
Satavaptan	DME5PN3	Acute and chronic heart failure	BD1Z	Phase 3	[9]
ASP-7035	DMTF24A	Nocturia	MF55	Phase 2	[10]
SPD-556	DM9OPK3	Heart failure	BD10-BD13	Phase 2	[5]
SSR149415	DMCMD93	Anxiety disorder	6B00-6B0Z	Phase 2	[11]
VA-106483	DM1ODP6	Nocturia	MF55	Phase 2	[12]

4 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
OPC-51803	DMDCOSP	Urinary incontinence	MF50.2	Discontinued in Phase 1	[13]
OX 19	DM5UYI7	Urinary incontinence	MF50.2	Discontinued in Phase 1	[14]
VNA-932	DMKRG0I	Urinary incontinence	MF50.2	Discontinued in Phase 1	[15]
JTV-605	DM89TXB	Dysmenorrhea	GA34.3	Terminated	[4]

34 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ARGENINE VASOPRESSIN	DM8KN0Q	Discovery agent	N.A.	Investigative	[16]
CL-385004	DMLQZGJ	Discovery agent	N.A.	Investigative	[4]
d(CH2)5[D-Ile2,Ile4]AVP	DMAX7LW	Discovery agent	N.A.	Investigative	[17]
D(CH2)5[Tyr(Me)2,Thr4,Orn8,Tyr9-NH2]VT	DM1BMT7	Discovery agent	N.A.	Investigative	[18]
d(CH2)5[Tyr(Me)2]AVP	DMHTSAX	Discovery agent	N.A.	Investigative	[17]
DVDAVP	DM53079	Discovery agent	N.A.	Investigative	[16]
D[Arg4,Dab8]VP	DMCU8HK	Discovery agent	N.A.	Investigative	[16]
D[Arg4,Lys8]VP	DM69OVM	Discovery agent	N.A.	Investigative	[16]
D[Arg4,Orn8]VP	DM8D4QT	Discovery agent	N.A.	Investigative	[16]
D[Arg4]AVP	DM76Q2B	Discovery agent	N.A.	Investigative	[16]
D[Cha4,Dab8]VP	DMCLUXI	Discovery agent	N.A.	Investigative	[16]
D[Cha4,Dap8]VP	DMAPZKB	Discovery agent	N.A.	Investigative	[16]
D[Cha4,Lys8]VP	DM0GO7U	Discovery agent	N.A.	Investigative	[16]
D[Cha4,Orn8]VP	DMZWTJK	Discovery agent	N.A.	Investigative	[16]
D[Cha4]AVP	DM8FCX5	Discovery agent	N.A.	Investigative	[16]
D[D-3-Pal2]AVP	DMD4V6U	Discovery agent	N.A.	Investigative	[16]
D[Leu4,Dab8]VP	DMNSXG9	Discovery agent	N.A.	Investigative	[16]
D[Leu4,Dap8]VP	DME3HK8	Discovery agent	N.A.	Investigative	[16]
D[Leu4,Lys8]VP	DMDBU7Q	Discovery agent	N.A.	Investigative	[16]
D[Leu4,Orn8]VP	DMJCW8Y	Discovery agent	N.A.	Investigative	[16]
D[Leu4]AVP	DMREZT7	Discovery agent	N.A.	Investigative	[16]
D[Orn4,Lys8]VP	DMNQTBU	Discovery agent	N.A.	Investigative	[16]
D[Orn4,Orn8]VP	DMONV0M	Discovery agent	N.A.	Investigative	[16]
D[Orn4]AVP	DMJNT95	Discovery agent	N.A.	Investigative	[16]
d[Pen1,Tyr(Me)2]AVP	DMT8KI6	Discovery agent	N.A.	Investigative	[17]
D[Val4]AVP	DM3GM8E	Discovery agent	N.A.	Investigative	[16]
FR161282	DMZSFEP	Discovery agent	N.A.	Investigative	[4]
L-372662	DMQV974	Discovery agent	N.A.	Investigative	[19]
VP-343	DMT03VB	Discovery agent	N.A.	Investigative	[4]
YM 218	DMPYM3J	Discovery agent	N.A.	Investigative	[20]
YM 471	DM5BFL4	Discovery agent	N.A.	Investigative	[21]
YM-35278	DMXRZ6N	Discovery agent	N.A.	Investigative	[22]
[Phe3]OT	DMK18CS	Discovery agent	N.A.	Investigative	[23]
[Val4]AVP	DMW82ZT	Discovery agent	N.A.	Investigative	[24]

References

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• [3] 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.
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• [5] 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. (Target id: 368).
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• [13] Effects 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.
• [14] Investigation 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.
• [15] Biased Agonist Pharmacochaperones of the AVP V2 Receptor May Treat Congenital Nephrogenic Diabetes Insipidus. J Am Soc Nephrol. 2009 October; 20(10): 2190-2203.
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• [17] Binding properties of a selective tritiated vasopressin V2 receptor antagonist, [H]-SR 121463. Kidney Int. 2000 Oct;58(4):1613-22.
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• [19] Oral oxytocin antagonists. J Med Chem. 2010 Sep 23;53(18):6525-38.
• [20] Effects of YM218, a nonpeptide vasopressin V1A receptor-selective antagonist, on human vasopressin and oxytocin receptors. Pharmacol Res. 2005 Mar;51(3):275-81.
• [21] Effects 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.
• [22] 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. Bioorg Med Chem. 2008 Nov 1;16(21):9524-35.
• [23] Tyr115 is the key residue for determining agonist selectivity in the V1a vasopressin receptor. EMBO J. 1995 May 15;14(10):2176-82.
• [24] [1-deamino-4-cyclohexylalanine] arginine vasopressin: a potent and specific agonist for vasopressin V1b receptors. Endocrinology. 2002 Dec;143(12):4655-64.