Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOHDWX1)

• DOT Name: Glucose-fructose oxidoreductase domain-containing protein 1 (GFOD1)
• Synonyms: EC 1.-.-.-
• Gene Name: GFOD1
• Related Disease:
  Acute myocardial infarction
  Clear cell renal carcinoma
• UniProt ID: GFOD1_HUMAN
• EC Number: 1.-.-.-
• Pfam ID: PF01408 ; PF02894
• Sequence:
  MLPGVGVFGTSLTARVIIPLLKDEGFAVKALWGRTQEEAEELAKEMSVPFYTSRIDEVLL
  HQDVDLVCINLPPPLTRQIAVKTLGIGKNVICDRTATPLDAFRMTSAAHYYPKLMSIMGN
  VLRFLPAFVRMKQLIEEGYVGEPLVCEVQVHGGSLLGKKYNWSCDDLMGGGGLHSVGTYI
  IDLLTFLTGQKAVKVHGLLKTFVKQTDHIKGIRQITSDDFCTFQMVLEGGVCCTVTLNFN
  VPGEFKQDVTVVGSAGRLLAVGTDLYGQRNSAPEQELLVQDATPVSNSLLPEKAFSDIPS
  PYLRGTIKMMQAVRQAFQDQDDRRTWDGRPLTMAATFDDCLYALCVVDTIKRSSQTGEWQ
  NIAIMTEEPELSPAYLISEAMRRSRMSLYC
• Reactome Pathway: RHOQ GTPase cycle (R-HSA-9013406)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myocardial infarction	DISE3HTG	Strong	Biomarker	[1]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[2]

12 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 Glucose-fructose oxidoreductase domain-containing protein 1 (GFOD1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Glucose-fructose oxidoreductase domain-containing protein 1 (GFOD1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Glucose-fructose oxidoreductase domain-containing protein 1 (GFOD1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Glucose-fructose oxidoreductase domain-containing protein 1 (GFOD1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Glucose-fructose oxidoreductase domain-containing protein 1 (GFOD1).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Glucose-fructose oxidoreductase domain-containing protein 1 (GFOD1).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Glucose-fructose oxidoreductase domain-containing protein 1 (GFOD1).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Glucose-fructose oxidoreductase domain-containing protein 1 (GFOD1).	[11]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Glucose-fructose oxidoreductase domain-containing protein 1 (GFOD1).	[12]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Glucose-fructose oxidoreductase domain-containing protein 1 (GFOD1).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Glucose-fructose oxidoreductase domain-containing protein 1 (GFOD1).	[14]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Glucose-fructose oxidoreductase domain-containing protein 1 (GFOD1).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Glucose-fructose oxidoreductase domain-containing protein 1 (GFOD1).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Glucose-fructose oxidoreductase domain-containing protein 1 (GFOD1).	[15]

References

• [1] Potential biomarkers of acute myocardial infarction based on weighted gene co-expression network analysis.Biomed Eng Online. 2019 Jan 25;18(1):9. doi: 10.1186/s12938-019-0625-6.
• [2] GFOD1 and peejar are promising markers for clear-cell renal cell carcinoma disease progression.Oncotarget. 2016 Jun 21;7(25):38004-38009. doi: 10.18632/oncotarget.9379.
• [3] A genomic approach to predict synergistic combinations for breast cancer treatment. Pharmacogenomics J. 2013 Feb;13(1):94-104. doi: 10.1038/tpj.2011.48. Epub 2011 Nov 15.
• [4] 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.
• [5] 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.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [9] 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.
• [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] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [13] 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.
• [14] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [15] 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.
• [16] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.