Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFYS4LO)

DOT Name	Neuromedin-S (NMS)
Gene Name	NMS
Related Disease	Acute myelogenous leukaemia ( ) Advanced cancer ( ) Cytomegalovirus infection ( ) Glioblastoma multiforme ( ) Inclusion body myopathy with Paget disease of bone and frontotemporal dementia ( ) Irritable bowel syndrome ( ) Malignant peripheral nerve sheath tumor ( ) Neoplasm ( ) Neurofibromatosis type 1 ( ) Parkinson disease ( ) Bone osteosarcoma ( ) Influenza ( ) Osteosarcoma ( ) Adult glioblastoma ( )
UniProt ID	NMS_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	7W56; 7W57
Sequence	MKHLRPQFPLILAIYCFCMLQIPSSGFPQPLADPSDGLDIVQLEQLAYCLSQWAPLSRQP KDNQDIYKRFLFHYSRTQEATHPVKTGFPPVHPLMHLAAKLANRRMKRILQRGSGTAAVD FTKKDHTATWGRPFFLFRPRNGRNIEDEAQIQW
Function	Implicated in the regulation of circadian rhythms through autocrine and/or paracrine actions.
KEGG Pathway	Neuroactive ligand-receptor interaction (hsa04080 )
Reactome Pathway	G alpha (q) signalling events (R-HSA-416476 ) G alpha (i) signalling events (R-HSA-418594 ) Peptide ligand-binding receptors (R-HSA-375276 )

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Acute myelogenous leukaemia	DISCSPTN	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Cytomegalovirus infection	DISCEMGC	Strong	Biomarker	[3]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[4]
Inclusion body myopathy with Paget disease of bone and frontotemporal dementia	DISK4S94	Strong	Genetic Variation	[5]
Irritable bowel syndrome	DIS27206	Strong	Biomarker	[6]
Malignant peripheral nerve sheath tumor	DIS0JTN6	Strong	Biomarker	[7]
Neoplasm	DISZKGEW	Strong	Altered Expression	[8]
Neurofibromatosis type 1	DIS53JH9	Strong	Biomarker	[7]
Parkinson disease	DISQVHKL	Strong	Biomarker	[9]
Bone osteosarcoma	DIST1004	moderate	Biomarker	[10]
Influenza	DIS3PNU3	moderate	Genetic Variation	[11]
Osteosarcoma	DISLQ7E2	moderate	Biomarker	[10]
Adult glioblastoma	DISVP4LU	Limited	Biomarker	[4]
------------------------------------------------------------------------------------


⏷ Show the Full List of 14 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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 Neuromedin-S (NMS).	[12]
------------------------------------------------------------------------------------

References

1	NMS-P937, an orally available, specific small-molecule polo-like kinase 1 inhibitor with antitumor activity in solid and hematologic malignancies.Mol Cancer Ther. 2012 Apr;11(4):1006-16. doi: 10.1158/1535-7163.MCT-11-0765. Epub 2012 Feb 7.
2	Discovery of Stereospecific PARP-1 Inhibitor Isoindolinone NMS-P515.ACS Med Chem Lett. 2019 Mar 13;10(4):534-538. doi: 10.1021/acsmedchemlett.8b00569. eCollection 2019 Apr 11.
3	The host ubiquitin-dependent segregase VCP/p97 is required for the onset of human cytomegalovirus replication.PLoS Pathog. 2017 May 11;13(5):e1006329. doi: 10.1371/journal.ppat.1006329. eCollection 2017 May.
4	Hsp90 inhibitor NMS-E973 exerts the anticancer effect against glioblastoma via induction of PUMA-mediated apoptosis.Onco Targets Ther. 2018 Mar 20;11:1583-1593. doi: 10.2147/OTT.S160813. eCollection 2018.
5	Specific inhibition of p97/VCP ATPase and kinetic analysis demonstrate interaction between D1 and D2 ATPase domains.J Mol Biol. 2014 Jul 29;426(15):2886-99. doi: 10.1016/j.jmb.2014.05.022. Epub 2014 May 27.
6	From psychology to physicality: how nerve growth factor transduces early life stress into gastrointestinal motility disorders later in life.Cell Cycle. 2019 Aug;18(16):1824-1829. doi: 10.1080/15384101.2019.1637203. Epub 2019 Jul 4.
7	Characterization and chemosensitivity of two human malignant peripheral nerve sheath tumour cell lines derived from a patient with neurofibromatosis type 1.Virchows Arch. 1998 Nov;433(5):435-41. doi: 10.1007/s004280050271.
8	Evaluation of [(11)C]NMS-E973 as a PET tracer for in vivo visualisation of HSP90.Theranostics. 2019 Jan 1;9(2):554-572. doi: 10.7150/thno.27213. eCollection 2019.
9	Predictive markers for Parkinson's disease using deep neural nets on neuromelanin sensitive MRI.Neuroimage Clin. 2019;22:101748. doi: 10.1016/j.nicl.2019.101748. Epub 2019 Mar 6.
10	Targeting polo-like kinase 1 by NMS-P937 in osteosarcoma cell lines inhibits tumor cell growth and partially overcomes drug resistance.Invest New Drugs. 2014 Dec;32(6):1167-80. doi: 10.1007/s10637-014-0158-6. Epub 2014 Sep 7.
11	Identification of NMS-873, an allosteric and specific p97 inhibitor, as a broad antiviral against both influenza A and B viruses.Eur J Pharm Sci. 2019 May 15;133:86-94. doi: 10.1016/j.ejps.2019.03.020. Epub 2019 Mar 28.
12	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.