Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO7MT28)

• DOT Name: Neuropeptide W (NPW)
• Synonyms: Preproprotein L8; hPPL8
• Gene Name: NPW
• Related Disease:
  Type-1 diabetes
  Adrenocortical carcinoma
  Anorexia nervosa cachexia
  High blood pressure
• UniProt ID: NPW_HUMAN
• Pfam ID: PF15180
• Sequence:
  MAWRPGERGAPASRPRLALLLLLLLLPLPSGAWYKHVASPRYHTVGRAAGLLMGLRRSPY
  LWRRALRAAAGPLARDTLSPEPAAREAPLLLPSWVQELWETRRRSSQAGIPVRAPRSPRA
  PEPALEPESLDFSGAGQRLRRDVSRPAVDPAANRLGLPCLAPGPF
• Function: Plays a regulatory role in the organization of neuroendocrine signals accessing the anterior pituitary gland. Stimulates water drinking and food intake. May play a role in the hypothalamic response to stress. NPW23 activates GPR7 and GPR8 more efficiently than NPW30.
• Tissue Specificity: Detected in cerebrospinal fluid and urine (at protein level) . Detected at high levels in the substantia nigra, fetal kidney and trachea; at lower levels in testis, uterus, ovary and placenta. Not detectable in many regions of the central nervous system. Also detected at high levels in lymphoblastic leukemia and colorectal adenocarcinoma.
• 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

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Type-1 diabetes	DIS7HLUB	Definitive	Biomarker	[1]
Adrenocortical carcinoma	DISZF4HX	Strong	Biomarker	[2]
Anorexia nervosa cachexia	DISFO5RQ	Strong	Biomarker	[3]
High blood pressure	DISY2OHH	moderate	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Neuropeptide W (NPW).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Neuropeptide W (NPW).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Neuropeptide W (NPW).	[7]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Neuropeptide W (NPW).	[8]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Neuropeptide W (NPW).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Neuropeptide W (NPW).	[11]

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 Neuropeptide W (NPW).	[10]

References

• [1] Neuropeptide B and neuropeptide W as new serum predictors of nutritional status and of clinical outcomes in pediatric patients with type 1 diabetes mellitus treated with the use of pens or insulin pumps.Arch Med Sci. 2019 May;15(3):619-631. doi: 10.5114/aoms.2018.75818. Epub 2018 May 16.
• [2] Neuropeptides B and W enhance the growth of human adrenocortical carcinoma-derived NCI-H295 cells by exerting MAPK p42/p44-mediated proliferogenic and antiapoptotic effects.Int J Mol Med. 2005 Dec;16(6):1021-8.
• [3] Neuropeptide B and Vaspin as New Biomarkers in Anorexia Nervosa.Biomed Res Int. 2018 Jun 10;2018:9727509. doi: 10.1155/2018/9727509. eCollection 2018.
• [4] Modulation of CaV1.2 calcium channel by neuropeptide W regulates vascular myogenic tone via G protein-coupled receptor 7.J Hypertens. 2015 Dec;33(12):2431-42. doi: 10.1097/HJH.0000000000000723.
• [5] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [6] 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.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [9] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [10] 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.
• [11] Genome-wide gene expression profiling of low-dose, long-term exposure of human osteosarcoma cells to bisphenol A and its analogs bisphenols AF and S. Toxicol In Vitro. 2015 Aug;29(5):1060-9.