Details of Drug Off-Target (DOT)

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

• DOT Name: Glutathione S-transferase omega-2 (GSTO2)
• Synonyms: GSTO-2; EC 2.5.1.18; Glutathione S-transferase omega 2-2; GSTO 2-2; Glutathione-dependent dehydroascorbate reductase; EC 1.8.5.1; Monomethylarsonic acid reductase; MMA(V) reductase; EC 1.20.4.2
• Gene Name: GSTO2
• UniProt ID: GSTO2_HUMAN
• PDB ID: 3Q18; 3Q19; 3QAG
• EC Number: 1.20.4.2; 1.8.5.1; 2.5.1.18
• Pfam ID: PF13417
• Sequence:
  MSGDATRTLGKGSQPPGPVPEGLIRIYSMRFCPYSHRTRLVLKAKDIRHEVVNINLRNKP
  EWYYTKHPFGHIPVLETSQCQLIYESVIACEYLDDAYPGRKLFPYDPYERARQKMLLELF
  CKVPHLTKECLVALRCGRECTNLKAALRQEFSNLEEILEYQNTTFFGGTCISMIDYLLWP
  WFERLDVYGILDCVSHTPALRLWISAMKWDPTVCALLMDKSIFQGFLNLYFQNNPNAFDF
  GLC
• Function: Exhibits glutathione-dependent thiol transferase activity. Has high dehydroascorbate reductase activity and may contribute to the recycling of ascorbic acid. Participates in the biotransformation of inorganic arsenic and reduces monomethylarsonic acid (MMA).
• Tissue Specificity: Expressed in a range of tissues, including the liver, kidney, skeletal muscle and prostate. Strongest expression in the testis.
• KEGG Pathway:
  Glutathione metabolism (hsa00480)
  Metabolism of xenobiotics by cytochrome P450 (hsa00980)
  Drug metabolism - cytochrome P450 (hsa00982)
  Drug metabolism - other enzymes (hsa00983)
  Metabolic pathways (hsa01100)
  Platinum drug resistance (hsa01524)
  Pathways in cancer (hsa05200)
  Chemical carcinogenesis - D. adducts (hsa05204)
  Chemical carcinogenesis - receptor activation (hsa05207)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
  Hepatocellular carcinoma (hsa05225)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  Vitamin C (ascorbate) metabolism (R-HSA-196836)
  Glutathione conjugation (R-HSA-156590)

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
Arsenic	DMTL2Y1	Approved	Glutathione S-transferase omega-2 (GSTO2) increases the response to substance of Arsenic.	[12]

11 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 Glutathione S-transferase omega-2 (GSTO2).	[1]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Glutathione S-transferase omega-2 (GSTO2).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Glutathione S-transferase omega-2 (GSTO2).	[3]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Glutathione S-transferase omega-2 (GSTO2).	[4]
Quercetin	DM3NC4M	Approved	Quercetin affects the expression of Glutathione S-transferase omega-2 (GSTO2).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Glutathione S-transferase omega-2 (GSTO2).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Glutathione S-transferase omega-2 (GSTO2).	[3]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Glutathione S-transferase omega-2 (GSTO2).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Glutathione S-transferase omega-2 (GSTO2).	[8]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Glutathione S-transferase omega-2 (GSTO2).	[9]
MG-132	DMKA2YS	Preclinical	MG-132 increases the expression of Glutathione S-transferase omega-2 (GSTO2).	[11]

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 increases the methylation of Glutathione S-transferase omega-2 (GSTO2).	[10]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] 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.
• [4] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [5] 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.
• [6] 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.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [9] 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.
• [10] 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.
• [11] Differential effects of arsenic species on Nrf2 and Bach1 nuclear localization in cultured hepatocytes. Toxicol Appl Pharmacol. 2021 Feb 15;413:115404. doi: 10.1016/j.taap.2021.115404. Epub 2021 Jan 9.
• [12] Association between arsenic metabolism gene polymorphisms and arsenic-induced skin lesions in individuals exposed to high-dose inorganic arsenic in northwest China. Sci Rep. 2018 Jan 11;8(1):413. doi: 10.1038/s41598-017-18925-3.