Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0U82T3)

• DOT Name: Neuropeptide B (NPB)
• Synonyms: Preproprotein L7; hPPL7
• Gene Name: NPB
• Related Disease:
  Niemann-pick disease
  Type-1 diabetes
  Anorexia nervosa cachexia
  Niemann-Pick disease type A
  Polycystic ovarian syndrome
  Progressive multifocal leukoencephalopathy
  Niemann-Pick disease type B
  Niemann-Pick disease type C
  Advanced cancer
• UniProt ID: NPB_HUMAN
• Pfam ID: PF15180
• Sequence:
  MARSATLAAAALALCLLLAPPGLAWYKPAAGHSSYSVGRAAGLLSGLRRSPYARRSQPYR
  GAEPPGGAGASPELQLHPRLRSLAVCVQDVAPNLQRCERLPDGRGTYQCKANVFLSLRAA
  DCLAA
• Function: May be involved in the regulation of feeding, neuroendocrine system, memory, learning and in the afferent pain pathway.
• Tissue Specificity: Widely expressed in the central nervous system. High levels are found in substantia nigra, hypothalamus, hippocampus, spinal cord, placenta and fetal brain; lower levels are found in testis, uterus and ovary. Also detected at high levels in 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

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Niemann-pick disease	DISKS5FO	Definitive	Biomarker	[1]
Type-1 diabetes	DIS7HLUB	Definitive	Biomarker	[2]
Anorexia nervosa cachexia	DISFO5RQ	Strong	Altered Expression	[3]
Niemann-Pick disease type A	DISRCINF	Strong	Biomarker	[4]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[5]
Progressive multifocal leukoencephalopathy	DISX02WS	Strong	Biomarker	[6]
Niemann-Pick disease type B	DISVJCFK	moderate	Genetic Variation	[7]
Niemann-Pick disease type C	DIS492ZO	moderate	Genetic Variation	[7]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[8]

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 Neuropeptide B (NPB).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Neuropeptide B (NPB).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Neuropeptide B (NPB).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Neuropeptide B (NPB).	[11]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Neuropeptide B (NPB).	[12]

References

• [1] Niemann-Pick disease type A and B are clinically but also enzymatically heterogeneous: pitfall in the laboratory diagnosis of sphingomyelinase deficiency associated with the mutation Q292 K.Neuropediatrics. 2003 Dec;34(6):301-6. doi: 10.1055/s-2003-44668.
• [2] 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.
• [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] Lung involvement in Niemann-Pick disease type C1: improvement with bronchoalveolar lavage.Neurol Sci. 2005 Jul;26(3):171-3. doi: 10.1007/s10072-005-0456-z.
• [5] Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles.J Clin Endocrinol Metab. 2011 Jun;96(6):1737-46. doi: 10.1210/jc.2010-2600. Epub 2011 Mar 16.
• [6] Use of a GFP-PML-expressing cell line as a biosensor for human cytomegalovirus infection.Methods Mol Biol. 2009;515:33-44. doi: 10.1007/978-1-59745-559-6_3.
• [7] Subclinical course of adult visceral Niemann-Pick type C1 disease. A rare or underdiagnosed disorder?.J Inherit Metab Dis. 2006 Aug;29(4):591. doi: 10.1007/s10545-006-0330-z. Epub 2006 Jun 26.
• [8] Morphology based scoring of chromosomal instability and its correlation with cell viability.Pathol Res Pract. 2017 Sep;213(9):1231-1234. doi: 10.1016/j.prp.2017.06.015. Epub 2017 Jul 1.
• [9] 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.
• [10] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [11] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [12] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [13] 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.