Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNE4THC)

• DOT Name: Nuclear autoantigenic sperm protein (NASP)
• Synonyms: NASP
• Gene Name: NASP
• Related Disease:
  Advanced cancer
  Gastric cancer
  Stomach cancer
  Carcinoma of liver and intrahepatic biliary tract
  Hepatocellular carcinoma
  Liver cancer
  Neoplasm
• UniProt ID: NASP_HUMAN
• PDB ID: 7V1K; 7V1L; 7V1M; 7V6P; 7V6Q
• Pfam ID: PF10516 ; PF13181
• Sequence:
  MAMESTATAAVAAELVSADKIEDVPAPSTSADKVESLDVDSEAKKLLGLGQKHLVMGDIP
  AAVNAFQEAASLLGKKYGETANECGEAFFFYGKSLLELARMENGVLGNALEGVHVEEEEG
  EKTEDESLVENNDNIDEEAREELREQVYDAMGEKEEAKKTEDKSLAKPETDKEQDSEMEK
  GGREDMDISKSAEEPQEKVDLTLDWLTETSEEAKGGAAPEGPNEAEVTSGKPEQEVPDAE
  EEKSVSGTDVQEECREKGGQEKQGEVIVSIEEKPKEVSEEQPVVTLEKQGTAVEVEAESL
  DPTVKPVDVGGDEPEEKVVTSENEAGKAVLEQLVGQEVPPAEESPEVTTEAAEASAVEAG
  SEVSEKPGQEAPVLPKDGAVNGPSVVGDQTPIEPQTSIERLTETKDGSGLEEKVRAKLVP
  SQEETKLSVEESEAAGDGVDTKVAQGATEKSPEDKVQIAANEETQEREEQMKEGEETEGS
  EEDDKENDKTEEMPNDSVLENKSLQENEEEEIGNLELAWDMLDLAKIIFKRQETKEAQLY
  AAQAHLKLGEVSVESENYVQAVEEFQSCLNLQEQYLEAHDRLLAETHYQLGLAYGYNSQY
  DEAVAQFSKSIEVIENRMAVLNEQVKEAEGSSAEYKKEIEELKELLPEIREKIEDAKESQ
  RSGNVAELALKATLVESSTSGFTPGGGGSSVSMIASRKPTDGASSSNCVTDISHLVRKKR
  KPEEESPRKDDAKKAKQEPEVNGGSGDAVPSGNEVSENMEEEAENQAESRAAVEGTVEAG
  ATVESTAC
• Function: Required for DNA replication, normal cell cycle progression and cell proliferation. Forms a cytoplasmic complex with HSP90 and H1 linker histones and stimulates HSP90 ATPase activity. NASP and H1 histone are subsequently released from the complex and translocate to the nucleus where the histone is released for binding to DNA.
• Tissue Specificity: Isoform 1 is testis- and sperm-specific.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Gastric cancer	DISXGOUK	moderate	Biomarker	[2]
Stomach cancer	DISKIJSX	moderate	Biomarker	[2]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Altered Expression	[3]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[3]
Liver cancer	DISDE4BI	Limited	Altered Expression	[3]
Neoplasm	DISZKGEW	Limited	Altered Expression	[3]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Nuclear autoantigenic sperm protein (NASP) increases the response to substance of Arsenic trioxide.	[29]

3 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 Nuclear autoantigenic sperm protein (NASP).	[4]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Nuclear autoantigenic sperm protein (NASP).	[24]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Nuclear autoantigenic sperm protein (NASP).	[24]

25 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 Nuclear autoantigenic sperm protein (NASP).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Nuclear autoantigenic sperm protein (NASP).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Nuclear autoantigenic sperm protein (NASP).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Nuclear autoantigenic sperm protein (NASP).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Nuclear autoantigenic sperm protein (NASP).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Nuclear autoantigenic sperm protein (NASP).	[10]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Nuclear autoantigenic sperm protein (NASP).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Nuclear autoantigenic sperm protein (NASP).	[11]
Selenium	DM25CGV	Approved	Selenium increases the expression of Nuclear autoantigenic sperm protein (NASP).	[12]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Nuclear autoantigenic sperm protein (NASP).	[13]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Nuclear autoantigenic sperm protein (NASP).	[14]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Nuclear autoantigenic sperm protein (NASP).	[15]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Nuclear autoantigenic sperm protein (NASP).	[16]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Nuclear autoantigenic sperm protein (NASP).	[17]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Nuclear autoantigenic sperm protein (NASP).	[18]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Nuclear autoantigenic sperm protein (NASP).	[19]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Nuclear autoantigenic sperm protein (NASP).	[20]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Nuclear autoantigenic sperm protein (NASP).	[21]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Nuclear autoantigenic sperm protein (NASP).	[22]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Nuclear autoantigenic sperm protein (NASP).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Nuclear autoantigenic sperm protein (NASP).	[23]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Nuclear autoantigenic sperm protein (NASP).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Nuclear autoantigenic sperm protein (NASP).	[26]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Nuclear autoantigenic sperm protein (NASP).	[27]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Nuclear autoantigenic sperm protein (NASP).	[28]

References

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• [2] microRNA-29c inhibits cell proliferation by targeting NASP in human gastric cancer.BMC Cancer. 2017 Feb 7;17(1):109. doi: 10.1186/s12885-017-3096-9.
• [3] NASP antagonize chromatin accessibility through maintaining histone H3K9me1 in hepatocellular carcinoma.Biochim Biophys Acta Mol Basis Dis. 2018 Oct;1864(10):3438-3448. doi: 10.1016/j.bbadis.2018.07.033. Epub 2018 Aug 1.
• [4] 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.
• [5] 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.
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• [8] 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.
• [9] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [10] 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.
• [11] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [12] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [13] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [14] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
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• [17] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [18] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [19] Gene expression signatures after ethanol exposure in differentiating embryoid bodies. Toxicol In Vitro. 2018 Feb;46:66-76.
• [20] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [21] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [22] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [23] 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.
• [24] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [25] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [26] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [27] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [28] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.
• [29] The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.