Details of Drug Off-Target (DOT)

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

• DOT Name: Neuronal pentraxin receptor (NPTXR)
• Gene Name: NPTXR
• Related Disease:
  Cardiac failure
  Congestive heart failure
  Advanced cancer
  Aorta coarctation
  Atrial fibrillation
  Dilated cardiomyopathy 1A
  High blood pressure
  Non-insulin dependent diabetes
  Small-cell lung cancer
  Stroke
  Type-1/2 diabetes
• UniProt ID: NPTXR_HUMAN
• Pfam ID: PF00354
• Sequence:
  MKFLAVLLAAGMLAFLGAVICIIASVPLAASPARALPGGADNASVASGAAASPGPQRSLS
  ALHGAGGSAGPPALPGAPAASAHPLPPGPLFSRFLCTPLAAACPSGAQQGDAAGAAPGER
  EELLLLQSTAEQLRQTALQQEARIRADQDTIRELTGKLGRCESGLPRGLQGAGPRRDTMA
  DGPWDSPALILELEDAVRALRDRIDRLEQELPARVNLSAAPAPVSAVPTGLHSKMDQLEG
  QLLAQVLALEKERVALSHSSRRQRQEVEKELDVLQGRVAELEHGSSAYSPPDAFKISIPI
  RNNYMYARVRKALPELYAFTACMWLRSRSSGTGQGTPFSYSVPGQANEIVLLEAGHEPME
  LLINDKVAQLPLSLKDNGWHHICIAWTTRDGLWSAYQDGELQGSGENLAAWHPIKPHGIL
  ILGQEQDTLGGRFDATQAFVGDIAQFNLWDHALTPAQVLGIANCTAPLLGNVLPWEDKLV
  EAFGGATKAAFDVCKGRAKA
• Function: May be involved in mediating uptake of synaptic material during synapse remodeling or in mediating the synaptic clustering of AMPA glutamate receptors at a subset of excitatory synapses.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiac failure	DISDC067	Definitive	Biomarker	[1]
Congestive heart failure	DIS32MEA	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Aorta coarctation	DISAFXDJ	Strong	Genetic Variation	[3]
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[4]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Genetic Variation	[5]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[3]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[6]
Small-cell lung cancer	DISK3LZD	Strong	Biomarker	[2]
Stroke	DISX6UHX	Strong	Biomarker	[7]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Neuronal pentraxin receptor (NPTXR).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Neuronal pentraxin receptor (NPTXR).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Neuronal pentraxin receptor (NPTXR).	[10]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Neuronal pentraxin receptor (NPTXR).	[11]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Neuronal pentraxin receptor (NPTXR).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Neuronal pentraxin receptor (NPTXR).	[13]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Neuronal pentraxin receptor (NPTXR).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Neuronal pentraxin receptor (NPTXR).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Neuronal pentraxin receptor (NPTXR).	[17]

2 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 Neuronal pentraxin receptor (NPTXR).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Neuronal pentraxin receptor (NPTXR).	[18]

References

• [1] Regulation of neuronal type genes in congestive heart failure rats.Acta Physiol (Oxf). 2006 Jan;186(1):17-27. doi: 10.1111/j.1748-1716.2005.01503.x.
• [2] Specific sensitivity of small cell lung cancer cell lines to the snake venom toxin taipoxin.Lung Cancer. 2005 Dec;50(3):329-37. doi: 10.1016/j.lungcan.2005.06.011. Epub 2005 Aug 22.
• [3] Human genotyping and an experimental model reveal NPR-C as a possible contributor to morbidity in coarctation of the aorta.Physiol Genomics. 2019 Jun 1;51(6):177-185. doi: 10.1152/physiolgenomics.00049.2018. Epub 2019 Apr 19.
• [4] NPR-C (Natriuretic Peptide Receptor-C) Modulates the Progression of Angiotensin II-Mediated Atrial Fibrillation and Atrial Remodeling in Mice.Circ Arrhythm Electrophysiol. 2019 Jan;12(1):e006863. doi: 10.1161/CIRCEP.118.006863.
• [5] Polymorphisms of beta-adrenoceptor and natriuretic peptide receptor genes influence the susceptibility to and the severity of idiopathic dilated cardiomyopathy in a Chinese cohort.J Card Fail. 2010 Jan;16(1):36-44. doi: 10.1016/j.cardfail.2009.08.003. Epub 2009 Sep 25.
• [6] Bioactive compounds in plant materials for the prevention of diabetesand obesity.Biosci Biotechnol Biochem. 2019 Jun;83(6):975-985. doi: 10.1080/09168451.2019.1580560. Epub 2019 Feb 17.
• [7] Comparison of self-reported and register-based hospital medical data on comorbidities in women.Sci Rep. 2019 Mar 5;9(1):3527. doi: 10.1038/s41598-019-40072-0.
• [8] 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.
• [9] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [10] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [11] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [13] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [14] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [15] 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.
• [16] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [17] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [18] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.