Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAVZ76K)

• DOT Name: Vasopressin-neurophysin 2-copeptin (AVP)
• Synonyms: AVP-NPII
• Gene Name: AVP
• Related Disease: Neurohypophyseal diabetes insipidus
• UniProt ID: NEU2_HUMAN
• PDB ID: 7BB6; 7BB7; 7DW9; 7KH0; 7R0C
• Pfam ID: PF00220 ; PF00184
• Sequence:
  MPDTMLPACFLGLLAFSSACYFQNCPRGGKRAMSDLELRQCLPCGPGGKGRCFGPSICCA
  DELGCFVGTAEALRCQEENYLPSPCQSGQKACGSGGRCAAFGVCCNDESCVTEPECREGF
  HRRARASDRSNATQLDGPAGALLLRLVQLAGAPEPFEPAQPDAY
• Function: [Neurophysin 2]: Specifically binds vasopressin.; [Arg-vasopressin]: Has a direct antidiuretic action on the kidney, it also causes vasoconstriction of the peripheral vessels. Acts by binding to vasopressin receptors (V1bR/AVPR1B, V1aR/AVPR1A, and V2R/AVPR2).
• KEGG Pathway:
  Phospholipase D sig.ling pathway (hsa04072)
  Neuroactive ligand-receptor interaction (hsa04080)
  Vascular smooth muscle contraction (hsa04270)
  Vasopressin-regulated water reabsorption (hsa04962)
• Reactome Pathway:
  Vasopressin-like receptors (R-HSA-388479)
  G alpha (q) signalling events (R-HSA-416476)
  G alpha (s) signalling events (R-HSA-418555)
  Vasopressin regulates renal water homeostasis via Aquaporins (R-HSA-432040)
  Defective AVP does not bind AVPR1A,B and causes neurohypophyseal diabetes insipidus (NDI) (R-HSA-5619099)
  Transport of organic anions (R-HSA-879518)
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  Defective AVP does not bind AVPR2 and causes neurohypophyseal diabetes insipidus (NDI) (R-HSA-9036092)
  BMAL1 (R-HSA-1368108)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neurohypophyseal diabetes insipidus	DISRZHB5	Strong	Autosomal dominant	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Insulin	DMB7CE0	Approved	Vasopressin-neurophysin 2-copeptin (AVP) increases the Hypoglycaemia ADR of Insulin.	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Vasopressin-neurophysin 2-copeptin (AVP).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Vasopressin-neurophysin 2-copeptin (AVP).	[14]

6 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Methotrexate increases the secretion of Vasopressin-neurophysin 2-copeptin (AVP).	[3]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the secretion of Vasopressin-neurophysin 2-copeptin (AVP).	[4]
Levodopa	DMN3E57	Approved	Levodopa decreases the secretion of Vasopressin-neurophysin 2-copeptin (AVP).	[7]
Hydrochlorothiazide	DMUSZHD	Approved	Hydrochlorothiazide affects the secretion of Vasopressin-neurophysin 2-copeptin (AVP).	[8]
Naloxone	DM3FXMA	Approved	Naloxone decreases the secretion of Vasopressin-neurophysin 2-copeptin (AVP).	[7]
Chlorpropamide	DMPHZQE	Approved	Chlorpropamide decreases the secretion of Vasopressin-neurophysin 2-copeptin (AVP).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Sodium chloride	DMM3950	Approved	Sodium chloride increases the expression of Vasopressin-neurophysin 2-copeptin (AVP).	[5]
Carvedilol	DMHTEAO	Approved	Carvedilol decreases the expression of Vasopressin-neurophysin 2-copeptin (AVP).	[6]
Luvox	DMJKROX	Approved	Luvox increases the expression of Vasopressin-neurophysin 2-copeptin (AVP).	[9]
Oxprenolol	DM51OQW	Approved	Oxprenolol decreases the expression of Vasopressin-neurophysin 2-copeptin (AVP).	[11]
Chlorpromazine	DMBGZI3	Phase 3 Trial	Chlorpromazine increases the expression of Vasopressin-neurophysin 2-copeptin (AVP).	[12]
G1	DMTV42K	Phase 1/2	G1 decreases the expression of Vasopressin-neurophysin 2-copeptin (AVP).	[13]
Apomorphine SL	DMPH7EO	Investigative	Apomorphine SL increases the expression of Vasopressin-neurophysin 2-copeptin (AVP).	[15]

References

• [1] Identification of five novel arginine vasopressin gene mutations in patients with familial neurohypophyseal diabetes insipidus. Int J Mol Med. 2016 Oct;38(4):1243-9. doi: 10.3892/ijmm.2016.2703. Epub 2016 Aug 11.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] [Increased secretion of vasopressin and edema formation in high dosage methotrexate therapy]. Z Gesamte Inn Med. 1988 Aug 1;43(15):411-4.
• [4] Urinary ET-1, AVP and sodium in premature infants treated with indomethacin and ibuprofen for patent ductus arteriosus. Pediatr Nephrol. 2005 Nov;20(11):1552-6. doi: 10.1007/s00467-005-2022-6. Epub 2005 Aug 17.
• [5] Osmoregulation of vasopressin and thirst: comparison of 20% mannitol with 5% saline as osmotic stimulants in healthy man. Clin Endocrinol (Oxf). 1994 Aug;41(2):207-12. doi: 10.1111/j.1365-2265.1994.tb02531.x.
• [6] Lower plasma noradrenaline and blood viscosity on carvedilol vs atenolol in men with recent myocardial infarction. Blood Press. 2002;11(6):377-84. doi: 10.1080/080370502321095357.
• [7] Blood pressure and vasopressin in progressive autonomic failure. Response to postural stimulation, L-dopa and naloxone. Brain. 1983 Jun;106 (Pt 2):503-11. doi: 10.1093/brain/106.2.503.
• [8] Thiazide-induced hyponatremia. South Med J. 1983 Nov;76(11):1363-7. doi: 10.1097/00007611-198311000-00009.
• [9] [Three cases of severe hyponatremia under taking selective serotonin reuptake inhibitor (SSRI)]. Nihon Jinzo Gakkai Shi. 2000 Oct;42(8):644-8.
• [10] Inappropriate secretion of antidiuretic hormone induced by chlorpropamide. Am J Med Sci. 1972 Mar;263(3):137-41. doi: 10.1097/00000441-197203000-00002.
• [11] Increased plasma vasopressin and serum uric acid in the low renin type of essential hypertension. Acta Med Scand. 1984;215(2):165-72. doi: 10.1111/j.0954-6820.1984.tb04988.x.
• [12] Antipsychotic drugs and plasma vasopressin in normals and acute schizophrenic patients. Biol Psychiatry. 1987 Apr;22(4):453-62. doi: 10.1016/0006-3223(87)90167-3.
• [13] The Selective Estrogen Receptor Modulator Raloxifene Regulates Arginine-Vasopressin Gene Expression in Human Female Neuroblastoma Cells Through G Protein-Coupled Estrogen Receptor and ERK Signaling. Endocrinology. 2015 Oct;156(10):3706-16. doi: 10.1210/en.2014-2010. Epub 2015 Jul 22.
• [14] 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.
• [15] Betamethasone does not prevent nausea and vomiting induced by the dopamine-agonist apomorphine. Can J Anaesth. 2006 Apr;53(4):370-4. doi: 10.1007/BF03022501.
• [16] 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.