Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEG25A2)

DOT Name	Neuropeptide S (NPS)
Gene Name	NPS
Related Disease	Anxiety disorder ( ) Chronic kidney disease ( ) Nail-patella syndrome ( ) Nephropathy ( ) Parkinsonian disorder ( ) Advanced cancer ( ) Alcohol dependence ( ) Alzheimer disease ( ) Analgesia ( ) Anxiety ( ) Breast cancer ( ) Breast carcinoma ( ) Cardiovascular disease ( ) Cognitive impairment ( ) Constipation ( ) Dementia ( ) Fibromyalgia ( ) Hypocalcemia ( ) Inflammatory bowel disease ( ) Intestinal disorder ( ) Mental disorder ( ) Non-insulin dependent diabetes ( ) Obsessive compulsive disorder ( ) Obstructive sleep apnea ( ) Panic disorder ( ) Polycystic kidney disease 1 ( ) Post-traumatic stress disorder ( ) Schizophrenia ( ) Sleep apnea syndrome ( ) Sleep disorder ( ) Substance abuse ( ) Neoplasm ( ) Asthma ( ) Cocaine addiction ( ) Type-1/2 diabetes ( )
UniProt ID	NPS_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF14993
Sequence	MISSVKLNLILVLSLSTMHVFWCYPVPSSKVSGKSDYFLILLNSCPTRLDRSKELAFLKP ILEKMFVKRSFRNGVGTGMKKTSFQRAKS
Function	Modulates arousal and anxiety. May play an important anorexigenic role. Binds to its receptor NPSR1 with nanomolar affinity to increase intracellular calcium concentrations.
KEGG Pathway	Neuroactive ligand-receptor interaction (hsa04080 )
Reactome Pathway	G alpha (q) signalling events (R-HSA-416476 ) G alpha (s) signalling events (R-HSA-418555 ) Peptide ligand-binding receptors (R-HSA-375276 )

Molecular Interaction Atlas (MIA) of This DOT

35 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Anxiety disorder	DISBI2BT	Definitive	Biomarker	[1]
Chronic kidney disease	DISW82R7	Definitive	Genetic Variation	[2]
Nail-patella syndrome	DIS8C4CT	Definitive	Genetic Variation	[3]
Nephropathy	DISXWP4P	Definitive	Genetic Variation	[4]
Parkinsonian disorder	DISHGY45	Definitive	Biomarker	[5]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[6]
Alcohol dependence	DIS4ZSCO	Strong	Biomarker	[7]
Alzheimer disease	DISF8S70	Strong	Biomarker	[8]
Analgesia	DISK3TVI	Strong	Biomarker	[9]
Anxiety	DISIJDBA	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[10]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[10]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[11]
Cognitive impairment	DISH2ERD	Strong	Biomarker	[12]
Constipation	DISRQXWI	Strong	Biomarker	[13]
Dementia	DISXL1WY	Strong	Biomarker	[14]
Fibromyalgia	DISZJDS2	Strong	Biomarker	[15]
Hypocalcemia	DISTCK2W	Strong	Biomarker	[16]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[17]
Intestinal disorder	DISGPMUQ	Strong	Altered Expression	[18]
Mental disorder	DIS3J5R8	Strong	Biomarker	[19]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[20]
Obsessive compulsive disorder	DIS1ZMM2	Strong	Biomarker	[21]
Obstructive sleep apnea	DIS0SVD1	Strong	Genetic Variation	[22]
Panic disorder	DISD3VNY	Strong	Biomarker	[23]
Polycystic kidney disease 1	DIS9FB3R	Strong	Altered Expression	[24]
Post-traumatic stress disorder	DISHL1EY	Strong	Biomarker	[25]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[21]
Sleep apnea syndrome	DISER6KS	Strong	Genetic Variation	[22]
Sleep disorder	DIS3JP1U	Strong	Biomarker	[26]
Substance abuse	DIS327VW	Strong	Biomarker	[27]
Neoplasm	DISZKGEW	Disputed	Biomarker	[28]
Asthma	DISW9QNS	Limited	Genetic Variation	[29]
Cocaine addiction	DISHTRXG	Limited	Biomarker	[30]
Type-1/2 diabetes	DISIUHAP	Limited	Genetic Variation	[31]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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 affects the methylation of Neuropeptide S (NPS).	[32]
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References

1	Sustained overexpression of neuropeptide S in the amygdala reduces anxiety-like behavior in rats.Behav Brain Res. 2019 Jul 23;367:28-34. doi: 10.1016/j.bbr.2019.03.039. Epub 2019 Mar 23.
2	Functional proteins involved in regulation of intracellular Ca(2+) for drug development: the extracellular calcium receptor and an innovative medical approach to control secondary hyperparathyroidism by calcimimetics.J Pharmacol Sci. 2005 Mar;97(3):355-60. doi: 10.1254/jphs.fmj04007x6. Epub 2005 Mar 17.
3	Limb and kidney defects in Lmx1b mutant mice suggest an involvement of LMX1B in human nail patella syndrome.Nat Genet. 1998 May;19(1):51-5. doi: 10.1038/ng0598-51.
4	Clinical and histological findings of autosomal dominant renal-limited disease with LMX1B mutation.Nephrology (Carlton). 2016 Sep;21(9):765-73. doi: 10.1111/nep.12666.
5	Central neuropeptide-S treatment improves neurofunctions of 6-OHDA-induced Parkinsonian rats.Exp Neurol. 2019 Jul;317:78-86. doi: 10.1016/j.expneurol.2019.02.015. Epub 2019 Feb 27.
6	Nutritional quality of food as represented by the FSAm-NPS nutrient profiling system underlying the Nutri-Score label and cancer risk in Europe: Results from the EPIC prospective cohort study.PLoS Med. 2018 Sep 18;15(9):e1002651. doi: 10.1371/journal.pmed.1002651. eCollection 2018 Sep.
7	Neuropeptide S receptor gene expression in alcohol withdrawal and protracted abstinence in postdependent rats.Alcohol Clin Exp Res. 2010 Jan;34(1):90-7. doi: 10.1111/j.1530-0277.2009.01070.x. Epub 2009 Oct 23.
8	Calcilytic NPS 2143 Reduces Amyloid Secretion and Increases sAPP Release from PSEN1 Mutant iPSC-Derived Neurons.J Alzheimers Dis. 2019;72(3):885-899. doi: 10.3233/JAD-190602.
9	Central noradrenergic activity affects analgesic effect of Neuropeptide S.J Anesth. 2018 Feb;32(1):48-53. doi: 10.1007/s00540-017-2427-y. Epub 2017 Nov 11.
10	Are self-reported unhealthy food choices associated with an increased risk of breast cancer? Prospective cohort study using the British Food Standards Agency nutrient profiling system.BMJ Open. 2017 Jun 8;7(6):e013718. doi: 10.1136/bmjopen-2016-013718.
11	Association between a dietary quality index based on the food standard agency nutrient profiling system and cardiovascular disease risk among French adults.Int J Cardiol. 2017 May 1;234:22-27. doi: 10.1016/j.ijcard.2017.02.092. Epub 2017 Feb 24.
12	Neuropeptide S Ameliorates Cognitive Impairment of APP/PS1 Transgenic Mice by Promoting Synaptic Plasticity and Reducing A Deposition.Front Behav Neurosci. 2019 Jun 25;13:138. doi: 10.3389/fnbeh.2019.00138. eCollection 2019.
13	Clinical Outcomes in Early Cervical Cancer Patients Treated with Nerve Plane-sparing Laparoscopic Radical Hysterectomy.J Minim Invasive Gynecol. 2020 Mar-Apr;27(3):687-696. doi: 10.1016/j.jmig.2019.04.025. Epub 2019 May 7.
14	Determinants of Cross-Sectional and Longitudinal Health-Related Quality of Life in Memory Clinic Patients Without Dementia.J Geriatr Psychiatry Neurol. 2020 Sep;33(5):256-264. doi: 10.1177/0891988719882104. Epub 2019 Oct 23.
15	Towards a neurophysiological signature for fibromyalgia.Pain. 2017 Jan;158(1):34-47. doi: 10.1097/j.pain.0000000000000707.
16	The Calcilytic Agent NPS 2143 Rectifies Hypocalcemia in a Mouse Model With an Activating Calcium-Sensing Receptor (CaSR) Mutation: Relevance to Autosomal Dominant Hypocalcemia Type 1 (ADH1).Endocrinology. 2015 Sep;156(9):3114-21. doi: 10.1210/en.2015-1269. Epub 2015 Jun 8.
17	Neuropeptide S inhibits gastrointestinal motility and increases mucosal permeability through nitric oxide.Am J Physiol Gastrointest Liver Physiol. 2015 Oct 15;309(8):G625-34. doi: 10.1152/ajpgi.00104.2015. Epub 2015 Jul 23.
18	Neuropeptide S receptor 1 expression in the intestine and skin--putative role in peptide hormone secretion.Neurogastroenterol Motil. 2010 Jan;22(1):79-87, e30. doi: 10.1111/j.1365-2982.2009.01366.x. Epub 2009 Jul 13.
19	The Physio-Pharmacological Role of the NPS/NPSR System in Psychiatric Disorders: A Translational Overview.Curr Protein Pept Sci. 2016;17(4):380-97. doi: 10.2174/1389203717666151218150704.
20	Prescribing for people with type 2 diabetes and renal impairment in Australian general practice: A national cross sectional study.Prim Care Diabetes. 2019 Apr;13(2):113-121. doi: 10.1016/j.pcd.2018.09.001. Epub 2018 Sep 24.
21	The functional coding variant Asn107Ile of the neuropeptide S receptor gene (NPSR1) influences age at onset of obsessive-compulsive disorder.Int J Neuropsychopharmacol. 2013 Oct;16(9):1951-8. doi: 10.1017/S1461145713000382. Epub 2013 May 17.
22	Non-synonymous polymorphism in the neuropeptide S precursor gene and sleep apnea.Sleep Breath. 2011 Sep;15(3):403-8. doi: 10.1007/s11325-010-0348-1. Epub 2010 Apr 21.
23	Modulation of prefrontal functioning in attention systems by NPSR1 gene variation.Neuroimage. 2015 Jul 1;114:199-206. doi: 10.1016/j.neuroimage.2015.03.064. Epub 2015 Apr 2.
24	Activation of Calcium-Sensing Receptor increases intracellular calcium and decreases cAMP and mTOR in PKD1 deficient cells.Sci Rep. 2018 Apr 9;8(1):5704. doi: 10.1038/s41598-018-23732-5.
25	Neuropeptide S in the basolateral amygdala mediates an adaptive behavioral stress response in a rat model of posttraumatic stress disorder by increasing the expression of BDNF and the neuropeptide YY1 receptor.Eur Neuropsychopharmacol. 2018 Jan;28(1):159-170. doi: 10.1016/j.euroneuro.2017.11.006. Epub 2017 Nov 20.
26	Neuropeptide S Counteracts Paradoxical Sleep Deprivation-Induced Anxiety-Like Behavior and Sleep Disturbances.Front Cell Neurosci. 2018 Mar 6;12:64. doi: 10.3389/fncel.2018.00064. eCollection 2018.
27	Mapping novel psychoactive substances policy in the EU: The case of Portugal, the Netherlands, Czech Republic, Poland, the United Kingdom and Sweden.PLoS One. 2019 Jun 26;14(6):e0218011. doi: 10.1371/journal.pone.0218011. eCollection 2019.
28	Prussian blue nanoparticles: Synthesis, surface modification, and application in cancer treatment.Int J Pharm. 2018 Oct 5;549(1-2):31-49. doi: 10.1016/j.ijpharm.2018.07.055. Epub 2018 Jul 24.
29	Neuropeptide S (NPS) variants modify the signaling and risk effects of NPS Receptor 1 (NPSR1) variants in asthma.PLoS One. 2017 May 2;12(5):e0176568. doi: 10.1371/journal.pone.0176568. eCollection 2017.
30	Synthesis and separation of the enantiomers of the neuropeptide S receptor antagonist (9R/S)-3-oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid 4-fluoro-benzylamide (SHA 68).J Med Chem. 2011 Apr 28;54(8):2738-44. doi: 10.1021/jm200138r. Epub 2011 Apr 5.
31	Use of SGLT2 inhibitors for diabetes and risk of infection: Analysis using general practice records from the NPS MedicineWise MedicineInsight program.Diabetes Res Clin Pract. 2017 Aug;130:180-185. doi: 10.1016/j.diabres.2017.06.018. Epub 2017 Jun 15.
32	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.