Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKVHCV0)

• DOT Name: Neuronal pentraxin-1 (NPTX1)
• Synonyms: NP1; Neuronal pentraxin I; NP-I
• Gene Name: NPTX1
• Related Disease:
  Hepatocellular carcinoma
  Alzheimer disease
  Amyloidosis
  Bipolar disorder
  Colon cancer
  Colon carcinoma
  Neoplasm
  Schizophrenia
  Spinocerebellar ataxia 50
  Lung cancer
  Lung carcinoma
  Cervical cancer
  Cervical carcinoma
  Gastric cancer
  Stomach cancer
  Colorectal carcinoma
  Helicoid peripapillary chorioretinal degeneration
  Sandhoff disease
  Tay-sachs disease
• UniProt ID: NPTX1_HUMAN
• PDB ID: 6YPE
• Pfam ID: PF00354
• Sequence:
  MPAGRAARTCALLALCLLGAGAQDFGPTRFICTSVPVDADMCAASVAAGGAEELRSSVLQ
  LRETVLQQKETILSQKETIRELTAKLGRCESQSTLDPGAGEARAGGGRKQPGSGKNTMGD
  LSRTPAAETLSQLGQTLQSLKTRLENLEQYSRLNSSSQTNSLKDLLQSKIDELERQVLSR
  VNTLEEGKGGPRNDTEERVKIETALTSLHQRISELEKGQKDNRPGDKFQLTFPLRTNYMY
  AKVKKSLPEMYAFTVCMWLKSSATPGVGTPFSYAVPGQANELVLIEWGNNPMEILINDKV
  AKLPFVINDGKWHHICVTWTTRDGVWEAYQDGTQGGSGENLAPYHPIKPQGVLVLGQEQD
  TLGGGFDATQAFVGELAHFNIWDRKLTPGEVYNLATCSTKALSGNVIAWAESHIEIYGGA
  TKWTFEACRQIN
• 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

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Amyloidosis	DISHTAI2	Strong	Biomarker	[3]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[4]
Colon cancer	DISVC52G	Strong	Biomarker	[5]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Schizophrenia	DISSRV2N	Strong	Biomarker	[4]
Spinocerebellar ataxia 50	DISN2Y44	Strong	Autosomal dominant	[6]
Lung cancer	DISCM4YA	moderate	Posttranslational Modification	[7]
Lung carcinoma	DISTR26C	moderate	Posttranslational Modification	[7]
Cervical cancer	DISFSHPF	Disputed	Altered Expression	[8]
Cervical carcinoma	DIST4S00	Disputed	Altered Expression	[8]
Gastric cancer	DISXGOUK	Disputed	Biomarker	[9]
Stomach cancer	DISKIJSX	Disputed	Biomarker	[9]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[10]
Helicoid peripapillary chorioretinal degeneration	DISFSS5N	Limited	Biomarker	[11]
Sandhoff disease	DISELKA4	Limited	Biomarker	[12]
Tay-sachs disease	DISWG5B4	Limited	Biomarker	[12]

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 Neuronal pentraxin-1 (NPTX1).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Neuronal pentraxin-1 (NPTX1).	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Neuronal pentraxin-1 (NPTX1).	[14]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Neuronal pentraxin-1 (NPTX1).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Neuronal pentraxin-1 (NPTX1).	[16]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of Neuronal pentraxin-1 (NPTX1).	[17]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Neuronal pentraxin-1 (NPTX1).	[18]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Neuronal pentraxin-1 (NPTX1).	[19]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Neuronal pentraxin-1 (NPTX1).	[20]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Neuronal pentraxin-1 (NPTX1).	[21]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Neuronal pentraxin-1 (NPTX1).	[22]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Neuronal pentraxin-1 (NPTX1).	[23]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Neuronal pentraxin-1 (NPTX1).	[24]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Neuronal pentraxin-1 (NPTX1).	[25]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Neuronal pentraxin-1 (NPTX1).	[27]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Neuronal pentraxin-1 (NPTX1).	[28]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Neuronal pentraxin-1 (NPTX1).	[29]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Neuronal pentraxin-1 (NPTX1).	[30]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Neuronal pentraxin-1 (NPTX1).	[31]

References

• [1] As a downstream target of the AKT pathway, NPTX1 inhibits proliferation and promotes apoptosis in hepatocellular carcinoma.Biosci Rep. 2019 Jun 4;39(6):BSR20181662. doi: 10.1042/BSR20181662. Print 2019 Jun 28.
• [2] Neuronal pentraxin 1: A synaptic-derived plasma biomarker in Alzheimer's disease.Neurobiol Dis. 2018 Jun;114:120-128. doi: 10.1016/j.nbd.2018.02.014. Epub 2018 Mar 6.
• [3] Neuronal pentraxin 1 contributes to the neuronal damage evoked by amyloid-beta and is overexpressed in dystrophic neurites in Alzheimer's brain.J Neurosci. 2006 Dec 6;26(49):12735-47. doi: 10.1523/JNEUROSCI.0575-06.2006.
• [4] Analysis of t(9;17)(q33.2;q25.3) chromosomal breakpoint regions and genetic association reveals novel candidate genes for bipolar disorder.Bipolar Disord. 2015 Mar;17(2):205-11. doi: 10.1111/bdi.12239. Epub 2014 Jul 23.
• [5] NPTX1 inhibits colon cancer cell proliferation through down-regulating cyclin A2 and CDK2 expression.Cell Biol Int. 2018 May;42(5):589-597. doi: 10.1002/cbin.10935. Epub 2018 Feb 6.
• [6] NPTX1 mutations trigger endoplasmic reticulum stress and cause autosomal dominant cerebellar ataxia. Brain. 2022 May 24;145(4):1519-1534. doi: 10.1093/brain/awab407.
• [7] NPTX1 is a novel epigenetic regulation gene and associated with prognosis in lung cancer.Biochem Biophys Res Commun. 2015 Mar 6;458(2):381-6. doi: 10.1016/j.bbrc.2015.01.124. Epub 2015 Jan 31.
• [8] Methylation markers for CCNA1 and C13ORF18 are strongly associated with high-grade cervical intraepithelial neoplasia and cervical cancer in cervical scrapings.Cancer Epidemiol Biomarkers Prev. 2009 Nov;18(11):3000-7. doi: 10.1158/1055-9965.EPI-09-0405. Epub 2009 Oct 20.
• [9] NPTX1 promotes metastasis via integrin/FAK signaling in gastric cancer.Cancer Manag Res. 2019 Apr 15;11:3237-3251. doi: 10.2147/CMAR.S196509. eCollection 2019.
• [10] Novel candidate colorectal cancer biomarkers identified by methylation microarray-based scanning.Endocr Relat Cancer. 2011 Jul 4;18(4):465-78. doi: 10.1530/ERC-11-0083. Print 2011 Aug.
• [11] Role of neuroparsin 1 in vitellogenesis in the mud crab, Scylla paramamosain.Gen Comp Endocrinol. 2020 Jan 1;285:113248. doi: 10.1016/j.ygcen.2019.113248. Epub 2019 Aug 17.
• [12] Neuronal pentraxin 1 depletion delays neurodegeneration and extends life in Sandhoff disease mice.Hum Mol Genet. 2017 Feb 15;26(4):661-673. doi: 10.1093/hmg/ddw422.
• [13] 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.
• [14] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [15] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [16] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [17] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [18] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [19] 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.
• [20] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [21] Unique signatures of stress-induced senescent human astrocytes. Exp Neurol. 2020 Dec;334:113466. doi: 10.1016/j.expneurol.2020.113466. Epub 2020 Sep 17.
• [22] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [23] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [24] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [25] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [26] 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.
• [27] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [28] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [29] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [30] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [31] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.