Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3WXFPR)

DOT Name	Pro-FMRFamide-related neuropeptide FF (NPFF)
Synonyms	FMRFamide-related peptides
Gene Name	NPFF
Related Disease	Analgesia ( ) Epilepsy ( ) Anxiety ( ) Anxiety disorder ( ) Neuroblastoma ( )
UniProt ID	NPFF_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF15085
Sequence	MDSRQAAALLVLLLLIDGGCAEGPGGQQEDQLSAEEDSEPLPPQDAQTSGSLLHYLLQAM ERPGRSQAFLFQPQRFGRNTQGSWRNEWLSPRAGEGLNSQFWSLAAPQRFGKK
Function	Morphine modulating peptides. Have wide-ranging physiologic effects, including the modulation of morphine-induced analgesia, elevation of arterial blood pressure, and increased somatostatin secretion from the pancreas. Neuropeptide FF potentiates and sensitizes ASIC1 and ASIC3 channels.
KEGG Pathway	Neuroactive ligand-receptor interaction (hsa04080 )
Reactome Pathway	G alpha (q) signalling events (R-HSA-416476 ) Orexin and neuropeptides FF and QRFP bind to their respective receptors (R-HSA-389397 )

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Analgesia	DISK3TVI	Strong	Biomarker	[1]
Epilepsy	DISBB28L	Strong	Biomarker	[2]
Anxiety	DISIJDBA	Limited	Biomarker	[3]
Anxiety disorder	DISBI2BT	Limited	Biomarker	[3]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[4]
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Molecular Interaction Atlas (MIA)

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Pro-FMRFamide-related neuropeptide FF (NPFF).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Pro-FMRFamide-related neuropeptide FF (NPFF).	[7]
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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 increases the methylation of Pro-FMRFamide-related neuropeptide FF (NPFF).	[6]
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References

1	Analgesic activities of the mixed opioid and NPFF receptors agonist DN-9 in a mouse model of formalin-induced orofacial inflammatory pain.Peptides. 2018 Dec;110:30-39. doi: 10.1016/j.peptides.2018.10.010. Epub 2018 Nov 1.
2	Neuropeptide FF receptors as novel targets for limbic seizure attenuation.Neuropharmacology. 2015 Aug;95:415-23. doi: 10.1016/j.neuropharm.2015.04.030. Epub 2015 May 9.
3	Identification and characterization of novel mammalian neuropeptide FF-like peptides that attenuate morphine-induced antinociception.J Biol Chem. 2001 Oct 5;276(40):36961-9. doi: 10.1074/jbc.M105308200. Epub 2001 Jul 31.
4	GRK2 protein-mediated transphosphorylation contributes to loss of function of -opioid receptors induced by neuropeptide FF (NPFF2) receptors.J Biol Chem. 2012 Apr 13;287(16):12736-49. doi: 10.1074/jbc.M111.314617. Epub 2012 Feb 28.
5	Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
6	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.
7	Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.