Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTH80PN)

• DOT Name: Probable glutathione peroxidase 8 (GPX8)
• Synonyms: GPx-8; GSHPx-8; EC 1.11.1.9
• Gene Name: GPX8
• UniProt ID: GPX8_HUMAN
• PDB ID: 3CYN; 3KIJ
• EC Number: 1.11.1.9
• Pfam ID: PF00255
• Sequence:
  MEPLAAYPLKCSGPRAKVFAVLLSIVLCTVTLFLLQLKFLKPKINSFYAFEVKDAKGRTV
  SLEKYKGKVSLVVNVASDCQLTDRNYLGLKELHKEFGPSHFSVLAFPCNQFGESEPRPSK
  EVESFARKNYGVTFPIFHKIKILGSEGEPAFRFLVDSSKKEPRWNFWKYLVNPEGQVVKF
  WKPEEPIEVIRPDIAALVRQVIIKKKEDL
• KEGG Pathway:
  Glutathione metabolism (hsa00480)
  Metabolic pathways (hsa01100)
  Thyroid hormone synthesis (hsa04918)
  Amyotrophic lateral sclerosis (hsa05014)
  Huntington disease (hsa05016)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
• Reactome Pathway: Detoxification of Reactive Oxygen Species (R-HSA-3299685)

Molecular Interaction Atlas (MIA) of This DOT

21 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 Probable glutathione peroxidase 8 (GPX8).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Probable glutathione peroxidase 8 (GPX8).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Probable glutathione peroxidase 8 (GPX8).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Probable glutathione peroxidase 8 (GPX8).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Probable glutathione peroxidase 8 (GPX8).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Probable glutathione peroxidase 8 (GPX8).	[2]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Probable glutathione peroxidase 8 (GPX8).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Probable glutathione peroxidase 8 (GPX8).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Probable glutathione peroxidase 8 (GPX8).	[8]
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the expression of Probable glutathione peroxidase 8 (GPX8).	[9]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Probable glutathione peroxidase 8 (GPX8).	[10]
Orlistat	DMRJSP8	Approved	Orlistat increases the expression of Probable glutathione peroxidase 8 (GPX8).	[11]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Probable glutathione peroxidase 8 (GPX8).	[12]
APR-246	DMNFADH	Phase 2	APR-246 affects the expression of Probable glutathione peroxidase 8 (GPX8).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Probable glutathione peroxidase 8 (GPX8).	[2]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Probable glutathione peroxidase 8 (GPX8).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Probable glutathione peroxidase 8 (GPX8).	[15]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Probable glutathione peroxidase 8 (GPX8).	[16]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Probable glutathione peroxidase 8 (GPX8).	[17]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Probable glutathione peroxidase 8 (GPX8).	[18]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Probable glutathione peroxidase 8 (GPX8).	[2]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] 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.
• [7] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [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] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [10] Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.
• [11] Inhibition of fatty-acid synthase induces caspase-8-mediated tumor cell apoptosis by up-regulating DDIT4. J Biol Chem. 2008 Nov 14;283(46):31378-84. doi: 10.1074/jbc.M803384200. Epub 2008 Sep 16.
• [12] Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
• [13] Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis. Oncogene. 2010 Mar 4;29(9):1329-38. doi: 10.1038/onc.2009.425. Epub 2009 Nov 30.
• [14] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [15] 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.
• [16] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
• [17] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [18] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.