Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDVWT5V)

• DOT Name: Small ribosomal subunit protein mS23 (MRPS23)
• Synonyms: 28S ribosomal protein S23, mitochondrial; MRP-S23; S23mt
• Gene Name: MRPS23
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Hepatocellular carcinoma
  Neoplasm
  Combined oxidative phosphorylation deficiency 46
• UniProt ID: RT23_HUMAN
• PDB ID: 3J9M ; 6NU2 ; 6NU3 ; 6RW4 ; 6RW5 ; 6VLZ ; 6VMI ; 6ZM5 ; 6ZM6 ; 6ZS9 ; 6ZSA ; 6ZSB ; 6ZSC ; 6ZSD ; 6ZSE ; 6ZSG ; 7A5F ; 7A5G ; 7A5I ; 7A5K ; 7L08 ; 7OG4 ; 7P2E ; 7PNX ; 7PNY ; 7PNZ ; 7PO0 ; 7PO1 ; 7PO2 ; 7PO3 ; 7QI4 ; 7QI5 ; 7QI6 ; 8ANY ; 8CSP ; 8CSQ ; 8CSR ; 8CSS ; 8CST ; 8CSU ; 8OIR ; 8OIS
• Pfam ID: PF10484
• Sequence:
  MAGSRLETVGSIFSRTRDLVRAGVLKEKPLWFDVYDAFPPLREPVFQRPRVRYGKAKAPI
  QDIWYHEDRIRAKFYSVYGSGQRAFDLFNPNFKSTCQRFVEKYTELQKLGETDEEKLFVE
  TGKALLAEGVILRRVGEARTQHGGSHVSRKSEHLSVRPQTALEENETQKEVPQDQHLEAP
  ADQSKGLLPP
• 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

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Combined oxidative phosphorylation deficiency 46	DISD25E9	Limited	Unknown	[4]

7 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 Small ribosomal subunit protein mS23 (MRPS23).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Small ribosomal subunit protein mS23 (MRPS23).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Small ribosomal subunit protein mS23 (MRPS23).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Small ribosomal subunit protein mS23 (MRPS23).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Small ribosomal subunit protein mS23 (MRPS23).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Small ribosomal subunit protein mS23 (MRPS23).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Small ribosomal subunit protein mS23 (MRPS23).	[11]

References

• [1] High MRPS23 expression contributes to hepatocellular carcinoma proliferation and indicates poor survival outcomes.Tumour Biol. 2017 Jul;39(7):1010428317709127. doi: 10.1177/1010428317709127.
• [2] Down-regulation of MRPS23 inhibits rat breast cancer proliferation and metastasis.Oncotarget. 2017 May 15;8(42):71772-71781. doi: 10.18632/oncotarget.17888. eCollection 2017 Sep 22.
• [3] An integrated genomics approach identifies drivers of proliferation in luminal-subtype human breast cancer.Nat Genet. 2014 Oct;46(10):1051-9. doi: 10.1038/ng.3073. Epub 2014 Aug 24.
• [4] A Comprehensive Genomic Analysis Reveals the Genetic Landscape of Mitochondrial Respiratory Chain Complex Deficiencies. PLoS Genet. 2016 Jan 7;12(1):e1005679. doi: 10.1371/journal.pgen.1005679. eCollection 2016 Jan.
• [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] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] 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.