Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPIYZU7)

• DOT Name: Prenylcysteine oxidase-like (PCYOX1L)
• Synonyms: EC 1.8.3.-
• Gene Name: PCYOX1L
• UniProt ID: PCYXL_HUMAN
• EC Number: 1.8.3.-
• Pfam ID: PF13450 ; PF07156
• Sequence:
  MARAAPLLAALTALLAAAAAGGDAPPGKIAVVGAGIGGSAVAHFLQQHFGPRVQIDVYEK
  GTVGGRLATISVNKQHYESGAASFHSLSLHMQDFVKLLGLRHRREVVGRSAIFGGEHFML
  EETDWYLLNLFRLWWHYGISFLRLQMWVEEVMEKFMRIYKYQAHGYAFSGVEELLYSLGE
  STFVNMTQHSVAESLLQVGVTQRFIDDVVSAVLRASYGQSAAMPAFAGAMSLAGAQGSLW
  SVEGGNKLVCSGLLKLTKANVIHATVTSVTLHSTEGKALYQVAYENEVGNSSDFYDIVVI
  ATPLHLDNSSSNLTFAGFHPPIDDVQGSFQPTVVSLVHGYLNSSYFGFPDPKLFPFANIL
  TTDFPSFFCTLDNICPVNISASFRRKQPQEAAVWRVQSPKPLFRTQLKTLFRSYYSVQTA
  EWQAHPLYGSRPTLPRFALHDQLFYLNALEWAASSVEVMAVAAKNVALLAYNRWYQDLDK
  IDQKDLMHKVKTEL
• Function: Probable oxidoreductase.
• Reactome Pathway: Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

14 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 Prenylcysteine oxidase-like (PCYOX1L).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Prenylcysteine oxidase-like (PCYOX1L).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Prenylcysteine oxidase-like (PCYOX1L).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Prenylcysteine oxidase-like (PCYOX1L).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Prenylcysteine oxidase-like (PCYOX1L).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Prenylcysteine oxidase-like (PCYOX1L).	[6]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Prenylcysteine oxidase-like (PCYOX1L).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Prenylcysteine oxidase-like (PCYOX1L).	[8]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Prenylcysteine oxidase-like (PCYOX1L).	[9]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Prenylcysteine oxidase-like (PCYOX1L).	[10]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Prenylcysteine oxidase-like (PCYOX1L).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Prenylcysteine oxidase-like (PCYOX1L).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Prenylcysteine oxidase-like (PCYOX1L).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Prenylcysteine oxidase-like (PCYOX1L).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Prenylcysteine oxidase-like (PCYOX1L).	[13]

References

• [1] 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.
• [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] 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.
• [5] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [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] 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.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [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] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [14] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.