Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7H7PM2)

• DOT Name: Large ribosomal subunit protein uL23m (MRPL23)
• Synonyms: 39S ribosomal protein L23, mitochondrial; L23mt; MRP-L23; L23 mitochondrial-related protein; Ribosomal protein L23-like
• Gene Name: MRPL23
• Related Disease:
  Epithelial ovarian cancer
  Ovarian cancer
  Ovarian neoplasm
• UniProt ID: RM23_HUMAN
• PDB ID: 3J7Y ; 3J9M ; 5OOL ; 5OOM ; 6I9R ; 6NU2 ; 6NU3 ; 6VLZ ; 6VMI ; 6ZM5 ; 6ZM6 ; 6ZS9 ; 6ZSA ; 6ZSB ; 6ZSC ; 6ZSD ; 6ZSE ; 6ZSG ; 7A5F ; 7A5G ; 7A5H ; 7A5I ; 7A5J ; 7A5K ; 7L08 ; 7L20 ; 7O9K ; 7O9M ; 7ODR ; 7ODS ; 7ODT ; 7OF0 ; 7OF2 ; 7OF3 ; 7OF4 ; 7OF5 ; 7OF6 ; 7OF7 ; 7OG4 ; 7OI6 ; 7OI7 ; 7OI8 ; 7OI9 ; 7OIA ; 7OIB ; 7OIC ; 7OID ; 7OIE ; 7PD3 ; 7PO4 ; 7QH6 ; 7QH7 ; 7QI4 ; 7QI5 ; 7QI6 ; 8ANY ; 8OIR ; 8OIT
• Pfam ID: PF00276
• Sequence:
  MARNVVYPLYRLGGPQLRVFRTNFFIQLVRPGVAQPEDTVQFRIPMEMTRVDLRNYLEGI
  YNVPVAAVRTRVQHGSNKRRDHRNVRIKKPDYKVAYVQLAHGQTFTFPDLFPEKDESPEG
  SAADDLYSMLEEERQQRQSSDPRRGGVPSWFGL
• KEGG Pathway: Ribosome (hsa03010)
• Reactome Pathway:
  Mitochondrial translation elongation (R-HSA-5389840)
  Mitochondrial translation termination (R-HSA-5419276)
  Mitochondrial translation initiation (R-HSA-5368286)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epithelial ovarian cancer	DIS56MH2	moderate	Genetic Variation	[1]
Ovarian cancer	DISZJHAP	moderate	Genetic Variation	[1]
Ovarian neoplasm	DISEAFTY	moderate	Genetic Variation	[1]

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 Large ribosomal subunit protein uL23m (MRPL23).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Large ribosomal subunit protein uL23m (MRPL23).	[11]

11 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 Large ribosomal subunit protein uL23m (MRPL23).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Large ribosomal subunit protein uL23m (MRPL23).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Large ribosomal subunit protein uL23m (MRPL23).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Large ribosomal subunit protein uL23m (MRPL23).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Large ribosomal subunit protein uL23m (MRPL23).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Large ribosomal subunit protein uL23m (MRPL23).	[8]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Large ribosomal subunit protein uL23m (MRPL23).	[9]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Large ribosomal subunit protein uL23m (MRPL23).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Large ribosomal subunit protein uL23m (MRPL23).	[12]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Large ribosomal subunit protein uL23m (MRPL23).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Large ribosomal subunit protein uL23m (MRPL23).	[14]

References

• [1] Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study.Hum Mol Genet. 2009 Jun 15;18(12):2297-304. doi: 10.1093/hmg/ddp138. Epub 2009 Mar 20.
• [2] 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.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [13] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [14] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.