Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTL9MHW)

• DTT Name: Vasopressin V1b receptor (V1BR)
• Synonyms: Vasopressin V3 receptor; Vasopressin V(1b) Receptor; VPR3; V1bR; Antidiuretic hormone receptor 1b; AVPR3; AVPR V3; AVPR V1b
• Gene Name: AVPR1B
• DTT Type: Successful target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: V1BR_HUMAN
• TTD ID: T59881
• Sequence:
  MDSGPLWDANPTPRGTLSAPNATTPWLGRDEELAKVEIGVLATVLVLATGGNLAVLLTLG
  QLGRKRSRMHLFVLHLALTDLAVALFQVLPQLLWDITYRFQGPDLLCRAVKYLQVLSMFA
  STYMLLAMTLDRYLAVCHPLRSLQQPGQSTYLLIAAPWLLAAIFSLPQVFIFSLREVIQG
  SGVLDCWADFGFPWGPRAYLTWTTLAIFVLPVTMLTACYSLICHEICKNLKVKTQAWRVG
  GGGWRTWDRPSPSTLAATTRGLPSRVSSINTISRAKIRTVKMTFVIVLAYIACWAPFFSV
  QMWSVWDKNAPDEDSTNVAFTISMLLGNLNSCCNPWIYMGFNSHLLPRPLRHLACCGGPQ
  PRMRRRLSDGSLSSRHTTLLTRSSCPATLSLSLSLTLSGRPRPEESPRDLELADGEGTAE
  TIIF
• Function: The activity of this receptor is mediated by G proteins which activate a phosphatidyl-inositol-calcium second messenger system. Receptor for arginine vasopressin.
• KEGG Pathway:
  Calcium signaling pathway (hsa04020)
  Neuroactive ligand-receptor interaction (hsa04080)
  Vascular smooth muscle contraction (hsa04270)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Vasopressin-like receptors (R-HSA-388479)

Molecular Interaction Atlas (MIA) of This DTT

4 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Desmopressin	DMS3GVE	Diabetic complication	5A2Y	Approved	[1]
Mozavaptan	DMZ905C	Hyponatraemia	5C72	Approved	[2]
Oxytocin	DMDL27I	Autism spectrum disorder	6A02	Approved	[3]
ATOSIBAN	DMB7WYM	N. A.	N. A.	Phase 4	[4]

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ABT-436	DMNAU1V	Anxiety disorder	6B00-6B0Z	Phase 2	[5]
SSR149415	DMCMD93	Anxiety disorder	6B00-6B0Z	Phase 2	[6]

35 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ARGENINE VASOPRESSIN	DM8KN0Q	Discovery agent	N.A.	Investigative	[7]
d(CH2)5[Tyr(Me)2]AVP	DMHTSAX	Discovery agent	N.A.	Investigative	[8]
D[Arg4,Dab8]VP	DMCU8HK	Discovery agent	N.A.	Investigative	[7]
D[Arg4,Lys8]VP	DM69OVM	Discovery agent	N.A.	Investigative	[7]
D[Arg4,Orn8]VP	DM8D4QT	Discovery agent	N.A.	Investigative	[7]
D[Arg4]AVP	DM76Q2B	Discovery agent	N.A.	Investigative	[7]
D[Cha4,Dab8]VP	DMCLUXI	Discovery agent	N.A.	Investigative	[7]
D[Cha4,Dap8]VP	DMAPZKB	Discovery agent	N.A.	Investigative	[7]
D[Cha4,Lys8]VP	DM0GO7U	Discovery agent	N.A.	Investigative	[7]
D[Cha4,Orn8]VP	DMZWTJK	Discovery agent	N.A.	Investigative	[7]
D[Cha4]AVP	DM8FCX5	Discovery agent	N.A.	Investigative	[7]
D[D-3-Pal2]AVP	DMD4V6U	Discovery agent	N.A.	Investigative	[7]
D[Leu4,Dab8]VP	DMNSXG9	Discovery agent	N.A.	Investigative	[7]
D[Leu4,Dap8]VP	DME3HK8	Discovery agent	N.A.	Investigative	[7]
D[Leu4,Lys8]VP	DMDBU7Q	Discovery agent	N.A.	Investigative	[7]
D[Leu4,Orn8]VP	DMJCW8Y	Discovery agent	N.A.	Investigative	[7]
D[Leu4]AVP	DMREZT7	Discovery agent	N.A.	Investigative	[7]
D[Lys8(5/6-Flu)]VT	DME2PKB	Discovery agent	N.A.	Investigative	[9]
D[Orn4,Lys8]VP	DMNQTBU	Discovery agent	N.A.	Investigative	[7]
D[Orn4,Orn8]VP	DMONV0M	Discovery agent	N.A.	Investigative	[7]
D[Orn4]AVP	DMJNT95	Discovery agent	N.A.	Investigative	[7]
D[Orn8(5/6C-Flu)]VT	DMH791N	Discovery agent	N.A.	Investigative	[9]
d[Pen1,Tyr(Me)2]AVP	DMT8KI6	Discovery agent	N.A.	Investigative	[10]
D[Thr4,Lys8(5/6C-Flu)]VT	DMS4F8O	Discovery agent	N.A.	Investigative	[9]
D[Thr4,Orn8(5/6C-Flu)]VT	DMBDZQA	Discovery agent	N.A.	Investigative	[9]
D[Val4]AVP	DM3GM8E	Discovery agent	N.A.	Investigative	[7]
YM 218	DMPYM3J	Discovery agent	N.A.	Investigative	[11]
YM 471	DM5BFL4	Discovery agent	N.A.	Investigative	[12]
[3H]nelivaptan	DM0163O	Discovery agent	N.A.	Investigative	[13]
[HO1][Lys8(5/6C-Flu)]VT	DMLZNK6	Discovery agent	N.A.	Investigative	[9]
[HO1][Orn8(5/6C-Flu)]VT	DMFK9V5	Discovery agent	N.A.	Investigative	[9]
[HO1][Thr4,Lys8(5/6C-Flu)]VT	DMT2UYR	Discovery agent	N.A.	Investigative	[9]
[HO1][Thr4,Orn8(5/6C-Flu)]VT	DM81B4W	Discovery agent	N.A.	Investigative	[9]
[Lys8(Alexa 488) ]PVA	DM7STF6	Discovery agent	N.A.	Investigative	[14]
[Val4]AVP	DMW82ZT	Discovery agent	N.A.	Investigative	[15]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Major depressive disorder	6A20	Pre-frontal cortex	5.14E-01	-0.03	-0.15

References

• [1] 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.
• [2] New analgesic drugs derived from phencyclidine. J Med Chem. 1981 May;24(5):496-9.
• [3] The human V3 pituitary vasopressin receptor: ligand binding profile and density-dependent signaling pathways. Endocrinology. 1997 Oct;138(10):4109-22.
• [4] The discovery of GSK221149A: a potent and selective oxytocin antagonist. Bioorg Med Chem Lett. 2008 Jan 1;18(1):90-4.
• [5] The vasopressin Avprlb receptor: Molecular and pharmacological studies. Stress. 2011 January; 14(1): 98-115.
• [6] Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008 Aug;33(9):2080-92.
• [7] 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.
• [8] 1-desamino-8-D-arginine vasopressin (DDAVP) as an agonist on V1b vasopressin receptor. Biochem Pharmacol. 1997 Jun 1;53(11):1711-7.
• [9] 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.
• [10] Pharmacological characterization of the human vasopressin receptor subtypes stably expressed in Chinese hamster ovary cells. Br J Pharmacol. 1998 Dec;125(7):1463-70.
• [11] Effects of YM218, a nonpeptide vasopressin V1A receptor-selective antagonist, on human vasopressin and oxytocin receptors. Pharmacol Res. 2005 Mar;51(3):275-81.
• [12] 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.
• [13] 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: 367).
• [14] 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.
• [15] [1-deamino-4-cyclohexylalanine] arginine vasopressin: a potent and specific agonist for vasopressin V1b receptors. Endocrinology. 2002 Dec;143(12):4655-64.