Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUEKZ18)

• DOT Name: Peroxiredoxin-5, mitochondrial (PRDX5)
• Synonyms: EC 1.11.1.24; Alu corepressor 1; Antioxidant enzyme B166; AOEB166; Liver tissue 2D-page spot 71B; PLP; Peroxiredoxin V; Prx-V; Peroxisomal antioxidant enzyme; TPx type VI; Thioredoxin peroxidase PMP20; Thioredoxin-dependent peroxiredoxin 5
• Gene Name: PRDX5
• UniProt ID: PRDX5_HUMAN
• PDB ID: 1H4O; 1HD2; 1OC3; 1URM; 2VL2; 2VL3; 2VL9; 3MNG; 4K7I; 4K7N; 4K7O; 4MMM
• EC Number: 1.11.1.24
• Pfam ID: PF08534
• Sequence:
  MGLAGVCALRRSAGYILVGGAGGQSAAAAARRYSEGEWASGGVRSFSRAAAAMAPIKVGD
  AIPAVEVFEGEPGNKVNLAELFKGKKGVLFGVPGAFTPGCSKTHLPGFVEQAEALKAKGV
  QVVACLSVNDAFVTGEWGRAHKAEGKVRLLADPTGAFGKETDLLLDDSLVSIFGNRRLKR
  FSMVVQDGIVKALNVEPDGTGLTCSLAPNIISQL
• Function: Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by detoxifying peroxides and as sensor of hydrogen peroxide-mediated signaling events.
• Tissue Specificity: Widely expressed.
• KEGG Pathway: Peroxisome (hsa04146)
• Reactome Pathway:
  (Name not found)
  Detoxification of Reactive Oxygen Species (R-HSA-3299685)
• BioCyc Pathway: MetaCyc:HS05016-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydrogen peroxide	DM1NG5W	Approved	Peroxiredoxin-5, mitochondrial (PRDX5) affects the response to substance of Hydrogen peroxide.	[9]

21 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Peroxiredoxin-5, mitochondrial (PRDX5).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Peroxiredoxin-5, mitochondrial (PRDX5).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Peroxiredoxin-5, mitochondrial (PRDX5).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Peroxiredoxin-5, mitochondrial (PRDX5).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Peroxiredoxin-5, mitochondrial (PRDX5).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Peroxiredoxin-5, mitochondrial (PRDX5).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Peroxiredoxin-5, mitochondrial (PRDX5).	[7]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Peroxiredoxin-5, mitochondrial (PRDX5).	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Peroxiredoxin-5, mitochondrial (PRDX5).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Peroxiredoxin-5, mitochondrial (PRDX5).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Peroxiredoxin-5, mitochondrial (PRDX5).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Peroxiredoxin-5, mitochondrial (PRDX5).	[12]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Peroxiredoxin-5, mitochondrial (PRDX5).	[1]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Peroxiredoxin-5, mitochondrial (PRDX5).	[13]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Peroxiredoxin-5, mitochondrial (PRDX5).	[14]
Cocaine	DMSOX7I	Approved	Cocaine affects the expression of Peroxiredoxin-5, mitochondrial (PRDX5).	[15]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Peroxiredoxin-5, mitochondrial (PRDX5).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Peroxiredoxin-5, mitochondrial (PRDX5).	[18]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Peroxiredoxin-5, mitochondrial (PRDX5).	[19]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Peroxiredoxin-5, mitochondrial (PRDX5).	[20]
Okadaic acid	DM47CO1	Investigative	Okadaic acid decreases the expression of Peroxiredoxin-5, mitochondrial (PRDX5).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Peroxiredoxin-5, mitochondrial (PRDX5).	[16]

References

• [1] 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.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] 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.
• [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] 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.
• [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] Nucleophosmin in the pathogenesis of arsenic-related bladder carcinogenesis revealed by quantitative proteomics. Toxicol Appl Pharmacol. 2010 Jan 15;242(2):126-35. doi: 10.1016/j.taap.2009.09.016. Epub 2009 Oct 7.
• [9] Quercetin induces the expression of peroxiredoxins 3 and 5 via the Nrf2/NRF1 transcription pathway. Invest Ophthalmol Vis Sci. 2011 Feb 22;52(2):1055-63. doi: 10.1167/iovs.10-5777.
• [10] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [11] Endoplasmic reticulum stress contributes to arsenic trioxide-induced intrinsic apoptosis in human umbilical and bone marrow mesenchymal stem cells. Environ Toxicol. 2016 Mar;31(3):314-28.
• [12] Proteomic analysis revealed association of aberrant ROS signaling with suberoylanilide hydroxamic acid-induced autophagy in Jurkat T-leukemia cells. Autophagy. 2010 Aug;6(6):711-24. doi: 10.4161/auto.6.6.12397. Epub 2010 Aug 17.
• [13] Antineoplastic effects of decitabine, an inhibitor of DNA promoter methylation, in adrenocortical carcinoma cells. Arch Surg. 2010 Mar;145(3):226-32. doi: 10.1001/archsurg.2009.292.
• [14] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [15] Proteomic analysis of the nucleus accumbens of rats with different vulnerability to cocaine addiction. Neuropharmacology. 2009 Jul;57(1):41-8. doi: 10.1016/j.neuropharm.2009.04.005. Epub 2009 Apr 22.
• [16] 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.
• [17] The genome-wide expression profile of Scrophularia ningpoensis-treated thapsigargin-stimulated U-87MG cells. Neurotoxicology. 2009 May;30(3):368-76.
• [18] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [19] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [20] Quercetin reduces oxidative damage induced by paraquat via modulating expression of antioxidant genes in A549 cells. J Appl Toxicol. 2013 Dec;33(12):1460-7. doi: 10.1002/jat.2812. Epub 2012 Sep 20.
• [21] Proteomic analysis reveals multiple patterns of response in cells exposed to a toxin mixture. Chem Res Toxicol. 2009 Jun;22(6):1077-85.