Details of Drug Off-Target (DOT)

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

DOT Name Prepronociceptin (PNOC)
Gene Name PNOC
Related Disease
Cognitive impairment ( )
Pachyonychia congenita ( )
Cocaine addiction ( )
Coxopodopatellar syndrome ( )
Depression ( )
Drug dependence ( )
Fibromyalgia ( )
Hypotension ( )
Mixed anxiety and depressive disorder ( )
Neonatal abstinence syndrome ( )
Neuroblastoma ( )
Non-small-cell lung cancer ( )
Parkinson disease ( )
Post-traumatic stress disorder ( )
Substance withdrawal syndrome ( )
Wilson disease ( )
Adult glioblastoma ( )
Alcohol withdrawal ( )
Glioblastoma multiforme ( )
Mood disorder ( )
Leishmaniasis ( )
Migraine disorder ( )
Alcohol dependence ( )
Asthma ( )
Autosomal recessive juvenile Parkinson disease 2 ( )
Juvenile-onset Parkinson disease ( )
Neuralgia ( )
Obesity ( )
Parkinsonian disorder ( )
Type-1/2 diabetes ( )
UniProt ID
PNOC_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
8F7X
Pfam ID
PF01160
Sequence
MKVLLCDLLLLSLFSSVFSSCQRDCLTCQEKLHPALDSFDLEVCILECEEKVFPSPLWTP
CTKVMARSSWQLSPAAPEHVAAALYQPRASEMQHLRRMPRVRSLFQEQEEPEPGMEEAGE
MEQKQLQKRFGGFTGARKSARKLANQKRFSEFMRQYLVLSMQSSQRRRTLHQNGNV
Function
[Nociceptin]: Ligand of the opioid receptor-like receptor OPRL1. It may act as a transmitter in the brain by modulating nociceptive and locomotor behavior. May be involved in neuronal differentiation and development; [Nocistatin]: Blocks nociceptin action in pain transmission by inhibiting nociceptin-induced hyperalgesia and allodynia; [Orphanin FQ2]: Has potent analgesic activity.
Tissue Specificity Predominantly expressed in the brain and spinal cord. Also expressed and secreted by peripheral blood neutrophils following degranulation.
KEGG Pathway
Neuroactive ligand-receptor interaction (hsa04080 )
Reactome Pathway
G alpha (i) signalling events (R-HSA-418594 )
Peptide ligand-binding receptors (R-HSA-375276 )

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Cognitive impairment DISH2ERD Definitive Biomarker [1]
Pachyonychia congenita DISW8VPN Definitive Altered Expression [2]
Cocaine addiction DISHTRXG Strong Altered Expression [3]
Coxopodopatellar syndrome DISMJAT7 Strong Biomarker [4]
Depression DIS3XJ69 Strong Biomarker [5]
Drug dependence DIS9IXRC Strong Biomarker [6]
Fibromyalgia DISZJDS2 Strong Genetic Variation [7]
Hypotension DISYNSM9 Strong Biomarker [8]
Mixed anxiety and depressive disorder DISV809X Strong Biomarker [9]
Neonatal abstinence syndrome DIS9OO80 Strong Genetic Variation [10]
Neuroblastoma DISVZBI4 Strong Altered Expression [11]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [12]
Parkinson disease DISQVHKL Strong Altered Expression [13]
Post-traumatic stress disorder DISHL1EY Strong Biomarker [14]
Substance withdrawal syndrome DISTT24U Strong Therapeutic [15]
Wilson disease DISVS9H7 Strong Altered Expression [16]
Adult glioblastoma DISVP4LU moderate Biomarker [17]
Alcohol withdrawal DIS7INCX moderate Biomarker [18]
Glioblastoma multiforme DISK8246 moderate Biomarker [17]
Mood disorder DISLVMWO moderate Biomarker [19]
Leishmaniasis DISABTW7 Disputed Genetic Variation [20]
Migraine disorder DISFCQTG Disputed Altered Expression [21]
Alcohol dependence DIS4ZSCO Limited Genetic Variation [22]
Asthma DISW9QNS Limited Biomarker [23]
Autosomal recessive juvenile Parkinson disease 2 DISNSTD1 Limited Biomarker [24]
Juvenile-onset Parkinson disease DISNT5BI Limited Biomarker [24]
Neuralgia DISWO58J Limited Biomarker [25]
Obesity DIS47Y1K Limited Biomarker [26]
Parkinsonian disorder DISHGY45 Limited Biomarker [24]
Type-1/2 diabetes DISIUHAP Limited Biomarker [27]
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⏷ Show the Full List of 30 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin increases the expression of Prepronociceptin (PNOC). [28]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Prepronociceptin (PNOC). [29]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Prepronociceptin (PNOC). [32]
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2 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 Prepronociceptin (PNOC). [30]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Prepronociceptin (PNOC). [31]
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References

1 Intra-nasal dopamine alleviates cognitive deficits in tgDISC1 rats which overexpress the human DISC1 gene.Neurobiol Learn Mem. 2017 Dec;146:12-20. doi: 10.1016/j.nlm.2017.10.015. Epub 2017 Oct 28.
2 Nociceptin/orphanin FQ opioid peptide-receptor expression in pachyonychia congenita.J Peripher Nerv Syst. 2018 Dec;23(4):241-248. doi: 10.1111/jns.12288. Epub 2018 Oct 16.
3 Potent and selective NOP receptor activation reduces cocaine self-administration in rats by lowering hedonic set point.Addict Biol. 2020 Nov;25(6):e12844. doi: 10.1111/adb.12844. Epub 2019 Nov 10.
4 Sex Differences in Nociceptin/Orphanin FQ Peptide Receptor-Mediated Pain and Anxiety Symptoms in a Preclinical Model of Post-traumatic Stress Disorder.Front Psychiatry. 2019 Jan 8;9:731. doi: 10.3389/fpsyt.2018.00731. eCollection 2018.
5 Role of nociceptin/orphanin FQ and nociceptin opioid peptide receptor in depression and antidepressant effects of nociceptin opioid peptide receptor antagonists.Korean J Physiol Pharmacol. 2019 Nov;23(6):427-448. doi: 10.4196/kjpp.2019.23.6.427. Epub 2019 Oct 24.
6 Genetic Deletion of the Nociceptin/Orphanin FQ Receptor in the Rat Confers Resilience to the Development of Drug Addiction.Neuropsychopharmacology. 2017 Feb;42(3):695-706. doi: 10.1038/npp.2016.171. Epub 2016 Aug 26.
7 Nociceptin/orphanin FQ receptor modulates painful and fatigue symptoms in a mouse model of fibromyalgia.Pain. 2019 Jun;160(6):1383-1401. doi: 10.1097/j.pain.0000000000001513.
8 Nociceptin receptor activation produces nitric oxide-mediated systemic hypotension.Life Sci. 2000;66(6):PL99-104. doi: 10.1016/s0024-3205(99)00627-x.
9 Nociceptin/orphanin FQ receptor agonists increase aggressiveness in the mouse resident-intruder test.Behav Brain Res. 2019 Jan 1;356:120-126. doi: 10.1016/j.bbr.2018.08.019. Epub 2018 Aug 22.
10 Association of maternal and infant variants in PNOC and COMT genes with neonatal abstinence syndrome severity.Am J Addict. 2017 Jan;26(1):42-49. doi: 10.1111/ajad.12483. Epub 2016 Dec 16.
11 The standardized Withania somnifera Dunal root extract alters basal and morphine-induced opioid receptor gene expression changes in neuroblastoma cells.BMC Complement Altern Med. 2018 Jan 10;18(1):9. doi: 10.1186/s12906-017-2065-9.
12 Nociceptin Receptor Is Overexpressed in Non-small Cell Lung Cancer and Predicts Poor Prognosis.Front Oncol. 2019 Apr 5;9:235. doi: 10.3389/fonc.2019.00235. eCollection 2019.
13 Anti-Parkinsonian and anti-dyskinetic profiles of two novel potent and selective nociceptin/orphanin FQ receptor agonists.Br J Pharmacol. 2018 Mar;175(5):782-796. doi: 10.1111/bph.14123. Epub 2018 Jan 31.
14 Decreased Nociceptin Receptors Are Related to Resilience and Recovery in College Women Who Have Experienced Sexual Violence: Therapeutic Implications for Posttraumatic Stress Disorder.Biol Psychiatry. 2019 Jun 15;85(12):1056-1064. doi: 10.1016/j.biopsych.2019.02.017. Epub 2019 Apr 4.
15 Orphanin FQ/nociceptin inhibits morphine withdrawal.Life Sci. 2000 Jan 14;66(8):PL119-23. doi: 10.1016/s0024-3205(99)00648-7.
16 Elevated plasma nociceptin level in patients with Wilson disease.Brain Res Bull. 2002 Jul;58(3):311-3. doi: 10.1016/s0361-9230(02)00795-5.
17 Nociceptin/orphanin FQ antagonizes lipopolysaccharide-stimulated proliferation, migration and inflammatory signaling in human glioblastoma U87 cells.Biochem Pharmacol. 2017 Sep 15;140:89-104. doi: 10.1016/j.bcp.2017.05.021. Epub 2017 Jun 2.
18 Nociceptin Receptors Upregulated in Cocaine Use Disorder: A Positron Emission Tomography Imaging Study Using [(11)C]NOP-1A.Am J Psychiatry. 2019 Jun 1;176(6):468-476. doi: 10.1176/appi.ajp.2019.18081007. Epub 2019 May 6.
19 Social defeat disrupts reward learning and potentiates striatal nociceptin/orphanin FQ mRNA in rats.Psychopharmacology (Berl). 2017 May;234(9-10):1603-1614. doi: 10.1007/s00213-017-4584-y. Epub 2017 Mar 9.
20 Molecular detection of the blood meal source of sand flies (Diptera: Psychodidae) in a transmission area of American cutaneous leishmaniasis, Paran State, Brazil.Acta Trop. 2015 Mar;143:8-12. doi: 10.1016/j.actatropica.2014.11.006. Epub 2014 Dec 18.
21 Circulating nociceptin and CGRP in medication-overuse headache.Acta Neurol Scand. 2019 Mar;139(3):269-275. doi: 10.1111/ane.13053. Epub 2018 Dec 11.
22 Nociceptin Receptors in Alcohol Use Disorders: APositron Emission Tomography Study Using [(11)C]NOP-1A.Biol Psychiatry. 2018 Nov 15;84(10):708-714. doi: 10.1016/j.biopsych.2017.05.019. Epub 2017 May 31.
23 Nociceptin reduces the inflammatory immune microenvironment in a conventional murine model of airway hyperresponsiveness.Clin Exp Allergy. 2017 Feb;47(2):208-216. doi: 10.1111/cea.12808. Epub 2016 Oct 5.
24 Nociceptin/Orphanin FQ Inhibits the Survival and Axon Growth of Midbrain Dopaminergic Neurons Through a p38-MAPK Dependent Mechanism.Mol Neurobiol. 2016 Dec;53(10):7284-7297. doi: 10.1007/s12035-015-9611-6. Epub 2015 Dec 21.
25 Analysis of the distribution of spinal NOP receptors in a chronic pain model using NOP-eGFP knock-in mice.Br J Pharmacol. 2018 Jul;175(13):2662-2675. doi: 10.1111/bph.14225. Epub 2018 May 6.
26 Nociceptin/orphanin FQ modulates energy homeostasis through inhibition of neurotransmission at VMN SF-1/ARC POMC synapses in a sex- and diet-dependent manner.Biol Sex Differ. 2019 Feb 12;10(1):9. doi: 10.1186/s13293-019-0220-3.
27 Effect of nociceptin on insulin release in normal and diabetic rat pancreas.Cell Tissue Res. 2018 Dec;374(3):517-529. doi: 10.1007/s00441-018-2903-1. Epub 2018 Aug 15.
28 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
29 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
30 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.
31 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
32 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.