Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4NLN6H)

• DOT Name: Neuromedin-B (NMB)
• Gene Name: NMB
• Related Disease:
  Cognitive impairment
  Vascular dementia
  Bardet biedl syndrome
  Carcinoid tumor
  Gastrin-producing neuroendocrine tumor
  Lung cancer
  Lung carcinoma
  Malignant soft tissue neoplasm
  Neoplasm
  Non-small-cell lung cancer
  Sarcoma
  Small-cell lung cancer
  Obesity
  Glaucoma/ocular hypertension
  Meningococcal disease
  Neuroblastoma
• UniProt ID: NMB_HUMAN
• PDB ID: 1C98; 1C9A
• Pfam ID: PF02044
• Sequence:
  MARRAGGARMFGSLLLFALLAAGVAPLSWDLPEPRSRASKIRVHSRGNLWATGHFMGKKS
  LEPSSPSPLGTAPHTSLRDQRLQLSHDLLGILLLKKALGVSLSRPAPQIQYRRLLVQILQ
  K
• Function: Stimulates smooth muscle contraction. Induces sighing by acting directly on the pre-Botzinger complex, a cluster of several thousand neurons in the ventrolateral medulla responsible for inspiration during respiratory activity. Contributes to the induction of sneezing following exposure to chemical irritants or allergens which causes release of NMB by nasal sensory neurons and activation of NMBR-expressing neurons in the sneeze-evoking region of the brainstem. These in turn activate neurons of the caudal ventral respiratory group, giving rise to the sneezing response. Contributes to induction of acute itch, possibly through activation of the NMBR receptor on dorsal root ganglion neurons. Increases expression of NMBR and steroidogenic mediators STAR, CYP11A1 and HSD3B1 in Leydig cells, induces secretion of testosterone by Leydig cells and also promotes Leydig cell proliferation. Plays a role in the innate immune response to influenza A virus infection by enhancing interferon alpha expression and reducing expression of IL6. Plays a role in CSF1-induced proliferation of osteoclast precursors by contributing to the positive regulation of the expression of the CSF1 receptor CSF1R.
• KEGG Pathway: Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cognitive impairment	DISH2ERD	Definitive	Biomarker	[1]
Vascular dementia	DISVO82H	Definitive	Biomarker	[1]
Bardet biedl syndrome	DISTBNZW	Strong	Biomarker	[2]
Carcinoid tumor	DISMNRDC	Strong	Biomarker	[3]
Gastrin-producing neuroendocrine tumor	DIS8TYKO	Strong	Biomarker	[4]
Lung cancer	DISCM4YA	Strong	Biomarker	[5]
Lung carcinoma	DISTR26C	Strong	Biomarker	[5]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Altered Expression	[6]
Neoplasm	DISZKGEW	Strong	Biomarker	[7]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[5]
Sarcoma	DISZDG3U	Strong	Altered Expression	[6]
Small-cell lung cancer	DISK3LZD	Strong	Altered Expression	[8]
Obesity	DIS47Y1K	moderate	Genetic Variation	[9]
Glaucoma/ocular hypertension	DISLBXBY	Limited	Biomarker	[10]
Meningococcal disease	DISGDM2Z	Limited	Biomarker	[11]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Neuromedin-B (NMB).	[13]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Neuromedin-B (NMB).	[14]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Neuromedin-B (NMB).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Neuromedin-B (NMB).	[16]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Neuromedin-B (NMB).	[17]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Neuromedin-B (NMB).	[18]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Neuromedin-B (NMB).	[19]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Neuromedin-B (NMB).	[20]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Neuromedin-B (NMB).	[21]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Neuromedin-B (NMB).	[22]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Neuromedin-B (NMB).	[23]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Neuromedin-B (NMB).	[24]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Neuromedin-B (NMB).	[25]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Neuromedin-B (NMB).	[20]
Prednisolone	DMQ8FR2	Approved	Prednisolone decreases the expression of Neuromedin-B (NMB).	[20]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone decreases the expression of Neuromedin-B (NMB).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Neuromedin-B (NMB).	[26]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Neuromedin-B (NMB).	[27]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Neuromedin-B (NMB).	[28]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Neuromedin-B (NMB).	[29]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Neuromedin-B (NMB).	[30]

References

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• [18] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [19] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
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• [23] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [24] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [25] Folic acid induces cell type-specific changes in the transcriptome of breast cancer cell lines: a proof-of-concept study. J Nutr Sci. 2016 Apr 26;5:e17. doi: 10.1017/jns.2016.8. eCollection 2016.
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• [27] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [28] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [29] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [30] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.