Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD2F4C8)

• DOT Name: Quinone oxidoreductase (CRYZ)
• Synonyms: EC 1.6.5.5; NADPH:quinone reductase; Zeta-crystallin
• Gene Name: CRYZ
• UniProt ID: QOR_HUMAN
• PDB ID: 1YB5
• EC Number: 1.6.5.5
• Pfam ID: PF08240 ; PF00107
• Sequence:
  MATGQKLMRAVRVFEFGGPEVLKLRSDIAVPIPKDHQVLIKVHACGVNPVETYIRSGTYS
  RKPLLPYTPGSDVAGVIEAVGDNASAFKKGDRVFTSSTISGGYAEYALAADHTVYKLPEK
  LDFKQGAAIGIPYFTAYRALIHSACVKAGESVLVHGASGGVGLAACQIARAYGLKILGTA
  GTEEGQKIVLQNGAHEVFNHREVNYIDKIKKYVGEKGIDIIIEMLANVNLSKDLSLLSHG
  GRVIVVGSRGTIEINPRDTMAKESSIIGVTLFSSTKEEFQQYAAALQAGMEIGWLKPVIG
  SQYPLEKVAEAHENIIHGSGATGKMILLL
• Function: Does not have alcohol dehydrogenase activity. Binds NADP and acts through a one-electron transfer process. Orthoquinones, such as 1,2-naphthoquinone or 9,10-phenanthrenequinone, are the best substrates (in vitro). May act in the detoxification of xenobiotics. Interacts with (AU)-rich elements (ARE) in the 3'-UTR of target mRNA species. Enhances the stability of mRNA coding for BCL2. NADPH binding interferes with mRNA binding.
• Tissue Specificity: Only very low amounts in the lens.

Molecular Interaction Atlas (MIA) of This DOT

16 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 Quinone oxidoreductase (CRYZ).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Quinone oxidoreductase (CRYZ).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Quinone oxidoreductase (CRYZ).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Quinone oxidoreductase (CRYZ).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Quinone oxidoreductase (CRYZ).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Quinone oxidoreductase (CRYZ).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Quinone oxidoreductase (CRYZ).	[7]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Quinone oxidoreductase (CRYZ).	[8]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Quinone oxidoreductase (CRYZ).	[9]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Quinone oxidoreductase (CRYZ).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Quinone oxidoreductase (CRYZ).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Quinone oxidoreductase (CRYZ).	[12]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Quinone oxidoreductase (CRYZ).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Quinone oxidoreductase (CRYZ).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Quinone oxidoreductase (CRYZ).	[15]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Quinone oxidoreductase (CRYZ).	[16]

References

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• [2] 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.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] Apoptosis, cell cycle progression and gene expression in TP53-depleted HCT116 colon cancer cells in response to short-term 5-fluorouracil treatment. Int J Oncol. 2007 Dec;31(6):1491-500.
• [10] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [11] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [12] 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.
• [13] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [14] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [16] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.