Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZWHU0N)

• DOT Name: Ribosomal protein eS27-like (RPS27L)
• Synonyms: 40S ribosomal protein S27-like; Small ribosomal subunit protein eS27-like
• Gene Name: RPS27L
• Related Disease:
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
• UniProt ID: RS27L_HUMAN
• Pfam ID: PF01667
• Sequence:
  MPLARDLLHPSLEEEKKKHKKKRLVQSPNSYFMDVKCPGCYKITTVFSHAQTVVLCVGCS
  TVLCQPTGGKARLTEGCSFRRKQH
• KEGG Pathway:
  Ribosome (hsa03010)
  Coro.virus disease - COVID-19 (hsa05171)
• Reactome Pathway:
  Peptide chain elongation (R-HSA-156902)
  SRP-dependent cotranslational protein targeting to membrane (R-HSA-1799339)
  Viral mRNA Translation (R-HSA-192823)
  Selenocysteine synthesis (R-HSA-2408557)
  Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226)
  Translation initiation complex formation (R-HSA-72649)
  Formation of a pool of free 40S subunits (R-HSA-72689)
  Formation of the ternary complex, and subsequently, the 43S complex (R-HSA-72695)
  Ribosomal scanning and start codon recognition (R-HSA-72702)
  GTP hydrolysis and joining of the 60S ribosomal subunit (R-HSA-72706)
  Eukaryotic Translation Termination (R-HSA-72764)
  Regulation of expression of SLITs and ROBOs (R-HSA-9010553)
  Response of EIF2AK4 (GCN2) to amino acid deficiency (R-HSA-9633012)
  SARS-CoV-1 modulates host translation machinery (R-HSA-9735869)
  SARS-CoV-2 modulates host translation machinery (R-HSA-9754678)
  Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) (R-HSA-975956)
  Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) (R-HSA-975957)
  L13a-mediated translational silencing of Ceruloplasmin expression (R-HSA-156827)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[2]

33 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 Ribosomal protein eS27-like (RPS27L).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ribosomal protein eS27-like (RPS27L).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ribosomal protein eS27-like (RPS27L).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Ribosomal protein eS27-like (RPS27L).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ribosomal protein eS27-like (RPS27L).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Ribosomal protein eS27-like (RPS27L).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Ribosomal protein eS27-like (RPS27L).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ribosomal protein eS27-like (RPS27L).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Ribosomal protein eS27-like (RPS27L).	[11]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Ribosomal protein eS27-like (RPS27L).	[12]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Ribosomal protein eS27-like (RPS27L).	[13]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Ribosomal protein eS27-like (RPS27L).	[14]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Ribosomal protein eS27-like (RPS27L).	[15]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Ribosomal protein eS27-like (RPS27L).	[16]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Ribosomal protein eS27-like (RPS27L).	[17]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Ribosomal protein eS27-like (RPS27L).	[18]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Ribosomal protein eS27-like (RPS27L).	[19]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Ribosomal protein eS27-like (RPS27L).	[20]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Ribosomal protein eS27-like (RPS27L).	[6]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Ribosomal protein eS27-like (RPS27L).	[20]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of Ribosomal protein eS27-like (RPS27L).	[20]
Ursodeoxycholic acid	DMCUT21	Approved	Ursodeoxycholic acid affects the expression of Ribosomal protein eS27-like (RPS27L).	[21]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil increases the expression of Ribosomal protein eS27-like (RPS27L).	[20]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ribosomal protein eS27-like (RPS27L).	[22]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Ribosomal protein eS27-like (RPS27L).	[23]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Ribosomal protein eS27-like (RPS27L).	[24]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Ribosomal protein eS27-like (RPS27L).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Ribosomal protein eS27-like (RPS27L).	[26]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Ribosomal protein eS27-like (RPS27L).	[19]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Ribosomal protein eS27-like (RPS27L).	[27]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Ribosomal protein eS27-like (RPS27L).	[28]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone affects the splicing of Ribosomal protein eS27-like (RPS27L).	[29]
Z-Pro-Prolinal	DM43O2U	Investigative	Z-Pro-Prolinal increases the expression of Ribosomal protein eS27-like (RPS27L).	[30]

References

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• [2] Ribosomal protein S27-like in colorectal cancer: a candidate for predicting prognoses.PLoS One. 2013 Jun 24;8(6):e67043. doi: 10.1371/journal.pone.0067043. Print 2013.
• [3] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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.
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• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] p53 hypersensitivity is the predominant mechanism of the unique responsiveness of testicular germ cell tumor (TGCT) cells to cisplatin. PLoS One. 2011 Apr 21;6(4):e19198. doi: 10.1371/journal.pone.0019198.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [13] 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.
• [14] 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.
• [15] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [16] 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.
• [17] 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.
• [18] Transcriptional profiling of MCF7 breast cancer cells in response to 5-Fluorouracil: relationship with cell cycle changes and apoptosis, and identification of novel targets of p53. Int J Cancer. 2006 Sep 1;119(5):1164-75.
• [19] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [20] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [21] Gene expression profiling of early primary biliary cirrhosis: possible insights into the mechanism of action of ursodeoxycholic acid. Liver Int. 2008 Aug;28(7):997-1010. doi: 10.1111/j.1478-3231.2008.01744.x. Epub 2008 Apr 15.
• [22] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [23] 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.
• [24] 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.
• [25] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [26] Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells. Toxicol Appl Pharmacol. 2010 Oct 15;248(2):111-21.
• [27] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [28] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [29] Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing-by-synthesis approach. BMC Genomics. 2006 Sep 29;7:246. doi: 10.1186/1471-2164-7-246.
• [30] Prolyl endopeptidase is involved in cellular signalling in human neuroblastoma SH-SY5Y cells. Neurosignals. 2011;19(2):97-109. doi: 10.1159/000326342. Epub 2011 Apr 10.