Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE8CQ7K)

• DOT Name: RRP15-like protein (RRP15)
• Synonyms: Ribosomal RNA-processing protein 15
• Gene Name: RRP15
• Related Disease: Advanced cancer
• UniProt ID: RRP15_HUMAN
• PDB ID: 8FKP; 8FKQ; 8FKR; 8FKS
• Pfam ID: PF07890
• Sequence:
  MAAAAPDSRVSEEENLKKTPKKKMKMVTGAVASVLEDEATDTSDSEGSCGSEKDHFYSDD
  DAIEADSEGDAEPCDKENENDGESSVGTNMGWADAMAKVLNKKTPESKPTILVKNKKLEK
  EKEKLKQERLEKIKQRDKRLEWEMMCRVKPDVVQDKETERNLQRIATRGVVQLFNAVQKH
  QKNVDEKVKEAGSSMRKRAKLISTVSKKDFISVLRGMDGSTNETASSRKKPKAKQTEVKS
  EEGPGWTILRDDFMMGASMKDWDKESDGPDDSRPESASDSDT

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Biomarker	[1]

18 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 RRP15-like protein (RRP15).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of RRP15-like protein (RRP15).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of RRP15-like protein (RRP15).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of RRP15-like protein (RRP15).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of RRP15-like protein (RRP15).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of RRP15-like protein (RRP15).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of RRP15-like protein (RRP15).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of RRP15-like protein (RRP15).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of RRP15-like protein (RRP15).	[10]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of RRP15-like protein (RRP15).	[11]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of RRP15-like protein (RRP15).	[12]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of RRP15-like protein (RRP15).	[13]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of RRP15-like protein (RRP15).	[14]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of RRP15-like protein (RRP15).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of RRP15-like protein (RRP15).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of RRP15-like protein (RRP15).	[2]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of RRP15-like protein (RRP15).	[18]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of RRP15-like protein (RRP15).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of RRP15-like protein (RRP15).	[16]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of RRP15-like protein (RRP15).	[16]

References

• [1] The roles of RRP15 in nucleolar formation, ribosome biogenesis and checkpoint control in human cells.Oncotarget. 2017 Feb 21;8(8):13240-13252. doi: 10.18632/oncotarget.14658.
• [2] 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.
• [3] 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.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer. Cancer Res. 2006 Mar 1;66(5):2765-77.
• [13] 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.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] 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.
• [16] 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.
• [17] 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.
• [18] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [19] Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.