Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKR8AFL)

• DOT Name: Vasopressin V1a receptor (AVPR1A)
• Synonyms: V1aR; AVPR V1a; Antidiuretic hormone receptor 1a; Vascular/hepatic-type arginine vasopressin receptor
• Gene Name: AVPR1A
• Related Disease: Autism spectrum disorder
• UniProt ID: V1AR_HUMAN
• PDB ID: 1YTV
• Pfam ID: PF00001 ; PF08983
• Sequence:
  MRLSAGPDAGPSGNSSPWWPLATGAGNTSREAEALGEGNGPPRDVRNEELAKLEIAVLAV
  TFAVAVLGNSSVLLALHRTPRKTSRMHLFIRHLSLADLAVAFFQVLPQMCWDITYRFRGP
  DWLCRVVKHLQVFGMFASAYMLVVMTADRYIAVCHPLKTLQQPARRSRLMIAAAWVLSFV
  LSTPQYFVFSMIEVNNVTKARDCWATFIQPWGSRAYVTWMTGGIFVAPVVILGTCYGFIC
  YNIWCNVRGKTASRQSKGAEQAGVAFQKGFLLAPCVSSVKSISRAKIRTVKMTFVIVTAY
  IVCWAPFFIIQMWSVWDPMSVWTESENPTITITALLGSLNSCCNPWIYMFFSGHLLQDCV
  QSFPCCQNMKEKFNKEDTDSMSRRQTFYSNNRSPTNSTGMWKDSPKSSKSIKFIPVST
• 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.
• KEGG Pathway:
  Calcium sig.ling pathway (hsa04020)
  Phospholipase D sig.ling pathway (hsa04072)
  Neuroactive ligand-receptor interaction (hsa04080)
  Vascular smooth muscle contraction (hsa04270)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Defective AVP does not bind AVPR1A,B and causes neurohypophyseal diabetes insipidus (NDI) (R-HSA-5619099)
  Vasopressin-like receptors (R-HSA-388479)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism spectrum disorder	DISXK8NV	Disputed	Unknown	[1]

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Dinoprostone	DMTYOPD	Approved	Vasopressin V1a receptor (AVPR1A) increases the Miosis ADR of Dinoprostone.	[11]
Alprostadil	DMWH7NQ	Approved	Vasopressin V1a receptor (AVPR1A) increases the Miosis ADR of Alprostadil.	[11]
Insulin	DMB7CE0	Approved	Vasopressin V1a receptor (AVPR1A) increases the Hypoglycaemia ADR of Insulin.	[11]
Dinoprost Tromethamine	DMXQKSL	Approved	Vasopressin V1a receptor (AVPR1A) increases the Miosis ADR of Dinoprost Tromethamine.	[11]

8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Vasopressin V1a receptor (AVPR1A).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Vasopressin V1a receptor (AVPR1A).	[3]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Vasopressin V1a receptor (AVPR1A).	[4]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Vasopressin V1a receptor (AVPR1A).	[5]
DTI-015	DMXZRW0	Approved	DTI-015 increases the expression of Vasopressin V1a receptor (AVPR1A).	[6]
Vasopressin	DMQ2FPC	Approved	Vasopressin increases the activity of Vasopressin V1a receptor (AVPR1A).	[7]
Bardoxolone methyl	DMODA2X	Phase 3	Bardoxolone methyl decreases the activity of Vasopressin V1a receptor (AVPR1A).	[8]
GW7647	DM9RD0C	Investigative	GW7647 increases the expression of Vasopressin V1a receptor (AVPR1A).	[10]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Vasopressin V1a receptor (AVPR1A).	[9]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [3] Functional cardiotoxicity assessment of cosmetic compounds using human-induced pluripotent stem cell-derived cardiomyocytes. Arch Toxicol. 2018 Jan;92(1):371-381.
• [4] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [5] Cell death mechanisms of the anti-cancer drug etoposide on human cardiomyocytes isolated from pluripotent stem cells. Arch Toxicol. 2018 Apr;92(4):1507-1524.
• [6] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [7] Characterizing fucoxanthin as a selective dopamine D(3)/D(4) receptor agonist: Relevance to Parkinson's disease. Chem Biol Interact. 2019 Sep 1;310:108757. doi: 10.1016/j.cbi.2019.108757. Epub 2019 Jul 16.
• [8] Characterization of the potent, selective Nrf2 activator, 3-(pyridin-3-ylsulfonyl)-5-(trifluoromethyl)-2H-chromen-2-one, in cellular and in vivo models of pulmonary oxidative stress. J Pharmacol Exp Ther. 2017 Oct;363(1):114-125.
• [9] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [10] Identifying qualitative differences in PPAR signaling networks in human and rat hepatocytes and their significance for next generation chemical risk assessment methods. Toxicol In Vitro. 2020 Apr;64:104463. doi: 10.1016/j.tiv.2019.02.017. Epub 2019 Oct 15.
• [11] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.