Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2829ZC)

• DOT Name: Nucleolar protein 16 (NOP16)
• Synonyms: HBV pre-S2 trans-regulated protein 3
• Gene Name: NOP16
• Related Disease:
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Liver cancer
  Precancerous condition
  Advanced cancer
  Gastric cancer
  Stomach cancer
  Neoplasm
• UniProt ID: NOP16_HUMAN
• PDB ID: 8FKP; 8FKQ; 8FKR; 8FKS; 8FKT; 8FKU; 8FKV; 8FKW; 8FKX; 8FKY
• Pfam ID: PF09420
• Sequence:
  MPKAKGKTRRQKFGYSVNRKRLNRNARRKAAPRIECSHIRHAWDHAKSVRQNLAEMGLAV
  DPNRAVPLRKRKVKAMEVDIEERPKELVRKPYVLNDLEAEASLPEKKGNTLSRDLIDYVR
  YMVENHGEDYKAMARDEKNYYQDTPKQIRSKINVYKRFYPAEWQDFLDSLQKRKMEVE

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[2]
Liver cancer	DISDE4BI	Strong	Biomarker	[3]
Precancerous condition	DISV06FL	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Disputed	Altered Expression	[4]
Gastric cancer	DISXGOUK	Disputed	Altered Expression	[4]
Stomach cancer	DISKIJSX	Disputed	Altered Expression	[4]
Neoplasm	DISZKGEW	Limited	Altered Expression	[1]

18 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 Nucleolar protein 16 (NOP16).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Nucleolar protein 16 (NOP16).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Nucleolar protein 16 (NOP16).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Nucleolar protein 16 (NOP16).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Nucleolar protein 16 (NOP16).	[9]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Nucleolar protein 16 (NOP16).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Nucleolar protein 16 (NOP16).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Nucleolar protein 16 (NOP16).	[12]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Nucleolar protein 16 (NOP16).	[12]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Nucleolar protein 16 (NOP16).	[13]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Nucleolar protein 16 (NOP16).	[14]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Nucleolar protein 16 (NOP16).	[15]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Nucleolar protein 16 (NOP16).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Nucleolar protein 16 (NOP16).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Nucleolar protein 16 (NOP16).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Nucleolar protein 16 (NOP16).	[19]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Nucleolar protein 16 (NOP16).	[20]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Nucleolar protein 16 (NOP16).	[21]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Nucleolar protein 16 (NOP16).	[18]

References

• [1] HSPC111 governs breast cancer growth by regulating ribosomal biogenesis.Mol Cancer Res. 2014 Apr;12(4):583-94. doi: 10.1158/1541-7786.MCR-13-0168. Epub 2014 Jan 14.
• [2] The estrogen and c-Myc target gene HSPC111 is over-expressed in breast cancer and associated with poor patient outcome.Breast Cancer Res. 2008;10(2):R28. doi: 10.1186/bcr1985. Epub 2008 Mar 29.
• [3] Multiple genes exhibit phenobarbital-induced constitutive active/androstane receptor-mediated DNA methylation changes during liver tumorigenesis and in liver tumors.Toxicol Sci. 2009 Apr;108(2):273-89. doi: 10.1093/toxsci/kfp031. Epub 2009 Feb 20.
• [4] Significant association of YAP1 and HSPC111 proteins with poor prognosis in Chinese gastric cancer patients.Oncotarget. 2017 May 17;8(46):80303-80314. doi: 10.18632/oncotarget.17932. eCollection 2017 Oct 6.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [7] Retinoic acid-induced downmodulation of telomerase activity in human cancer cells. Exp Mol Pathol. 2005 Oct;79(2):108-17.
• [8] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [9] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Gene expression profile of human lymphoid CEM cells sensitive and resistant to glucocorticoid-evoked apoptosis. Genomics. 2003 Jun;81(6):543-55.
• [14] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [15] 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.
• [16] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [17] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [18] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [19] 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.
• [20] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [21] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.