Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ97TF3)

• DOT Name: N-glycosylase/DNA lyase (OGG1)
• Gene Name: OGG1
• UniProt ID: OGG1_HUMAN
• PDB ID: 1EBM; 1FN7; 1HU0; 1KO9; 1LWV; 1LWW; 1LWY; 1M3H; 1M3Q; 1N39; 1N3A; 1N3C; 1YQK; 1YQL; 1YQM; 1YQR; 2I5W; 2NOB; 2NOE; 2NOF; 2NOH; 2NOI; 2NOL; 2NOZ; 2XHI; 3IH7; 3KTU; 5AN4; 6RLW; 6W0M; 6W0R; 6W13; 7AYY
• EC Number: 3.2.2.-; 4.2.99.18
• Pfam ID: PF00730 ; PF07934
• Sequence:
  MPARALLPRRMGHRTLASTPALWASIPCPRSELRLDLVLPSGQSFRWREQSPAHWSGVLA
  DQVWTLTQTEEQLHCTVYRGDKSQASRPTPDELEAVRKYFQLDVTLAQLYHHWGSVDSHF
  QEVAQKFQGVRLLRQDPIECLFSFICSSNNNIARITGMVERLCQAFGPRLIQLDDVTYHG
  FPSLQALAGPEVEAHLRKLGLGYRARYVSASARAILEEQGGLAWLQQLRESSYEEAHKAL
  CILPGVGTKVADCICLMALDKPQAVPVDVHMWHIAQRDYSWHPTTSQAKGPSPQTNKELG
  NFFRSLWGPYAGWAQAVLFSADLRQSRHAQEPPAKRRKGSKGPEG
• Function: DNA repair enzyme that incises DNA at 8-oxoG residues. Excises 7,8-dihydro-8-oxoguanine and 2,6-diamino-4-hydroxy-5-N-methylformamidopyrimidine (FAPY) from damaged DNA. Has a beta-lyase activity that nicks DNA 3' to the lesion.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway: Base excision repair (hsa03410)
• Reactome Pathway:
  (Name not found)
  Cleavage of the damaged pyrimidine (R-HSA-110329)
  Recognition and association of DNA glycosylase with site containing an affected purine (R-HSA-110330)
  Cleavage of the damaged purine (R-HSA-110331)
  Displacement of DNA glycosylase by APEX1 (R-HSA-110357)
  APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway (R-HSA-5649702)
  Defective OGG1 Substrate Binding (R-HSA-9656255)
  Defective OGG1 Substrate Processing (R-HSA-9656256)
  Recognition and association of DNA glycosylase with site containing an affected pyrimidine (R-HSA-110328)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
DTI-015	DMXZRW0	Approved	N-glycosylase/DNA lyase (OGG1) decreases the response to substance of DTI-015.	[17]
Thiotepa	DMIZKOP	Approved	N-glycosylase/DNA lyase (OGG1) decreases the response to substance of Thiotepa.	[17]
Paraquat	DMR8O3X	Investigative	N-glycosylase/DNA lyase (OGG1) affects the response to substance of Paraquat.	[18]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
8-hydroxyguanine	DMT9BPN	Investigative	N-glycosylase/DNA lyase (OGG1) decreases the abundance of 8-hydroxyguanine.	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of N-glycosylase/DNA lyase (OGG1).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of N-glycosylase/DNA lyase (OGG1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of N-glycosylase/DNA lyase (OGG1).	[3]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of N-glycosylase/DNA lyase (OGG1).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of N-glycosylase/DNA lyase (OGG1).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of N-glycosylase/DNA lyase (OGG1).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of N-glycosylase/DNA lyase (OGG1).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of N-glycosylase/DNA lyase (OGG1).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of N-glycosylase/DNA lyase (OGG1).	[4]
Selenium	DM25CGV	Approved	Selenium increases the expression of N-glycosylase/DNA lyase (OGG1).	[5]
Menadione	DMSJDTY	Approved	Menadione increases the expression of N-glycosylase/DNA lyase (OGG1).	[8]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of N-glycosylase/DNA lyase (OGG1).	[9]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of N-glycosylase/DNA lyase (OGG1).	[10]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of N-glycosylase/DNA lyase (OGG1).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of N-glycosylase/DNA lyase (OGG1).	[12]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of N-glycosylase/DNA lyase (OGG1).	[10]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of N-glycosylase/DNA lyase (OGG1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of N-glycosylase/DNA lyase (OGG1).	[13]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of N-glycosylase/DNA lyase (OGG1).	[15]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos decreases the expression of N-glycosylase/DNA lyase (OGG1).	[16]

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 increases the methylation of N-glycosylase/DNA lyase (OGG1).	[14]

References

• [1] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [2] 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.
• [3] Exploring pradimicin-IRD antineoplastic mechanisms and related DNA repair pathways. Chem Biol Interact. 2023 Feb 1;371:110342. doi: 10.1016/j.cbi.2023.110342. Epub 2023 Jan 10.
• [4] DNA demethylation by 5-aza-2-deoxycytidine treatment abrogates 17 beta-estradiol-induced cell growth and restores expression of DNA repair genes in human breast cancer cells. Cancer Lett. 2012 Mar;316(1):62-9. doi: 10.1016/j.canlet.2011.10.022. Epub 2011 Oct 23.
• [5] High selenium status in individuals exposed to arsenic through coal-burning in Shaanxi (PR of China) modulates antioxidant enzymes, heme oxygenase-1 and DNA damage. Clin Chim Acta. 2010 Sep 6;411(17-18):1312-8.
• [6] Quercetin inhibits hydrogen peroxide-induced DNA damage and enhances DNA repair in Caco-2 cells. Food Chem Toxicol. 2009 Nov;47(11):2716-22. doi: 10.1016/j.fct.2009.07.033. Epub 2009 Aug 3.
• [7] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [8] Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
• [9] Higher Concentrations of Folic Acid Cause Oxidative Stress, Acute Cytotoxicity, and Long-Term Fibrogenic Changes in Kidney Epithelial Cells. Chem Res Toxicol. 2022 Nov 21;35(11):2168-2179. doi: 10.1021/acs.chemrestox.2c00258. Epub 2022 Nov 10.
• [10] Differences in the activities of resveratrol and ascorbic acid in protection of ethanol-induced oxidative DNA damage in human peripheral lymphocytes. Food Chem Toxicol. 2012 Feb;50(2):168-74.
• [11] Proteomic analysis of anti-cancer effects by paclitaxel treatment in cervical cancer cells. Gynecol Oncol. 2005 Jul;98(1):45-53. doi: 10.1016/j.ygyno.2005.04.010.
• [12] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [13] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [14] Genome-wide distribution of histone trimethylation reveals a global impact of bisphenol A on telomeric binding proteins and histone acetyltransferase factors: a pilot study with human and in vitro data. Clin Epigenetics. 2022 Dec 26;14(1):186. doi: 10.1186/s13148-022-01408-2.
• [15] Glyphosate-based herbicides at low doses affect canonical pathways in estrogen positive and negative breast cancer cell lines. PLoS One. 2019 Jul 11;14(7):e0219610. doi: 10.1371/journal.pone.0219610. eCollection 2019.
• [16] APE1 modulates cellular responses to organophosphate pesticide-induced oxidative damage in non-small cell lung carcinoma A549 cells. Mol Cell Biochem. 2018 Apr;441(1-2):201-216.
• [17] Protection of mammalian cells against chemotherapeutic agents thiotepa, 1,3-N,N'-bis(2-chloroethyl)-N-nitrosourea, and mafosfamide using the DNA base excision repair genes Fpg and alpha-hOgg1: implications for protective gene therapy applications. J Pharmacol Exp Ther. 2001 Mar;296(3):825-31.
• [18] Editor's Highlight: Base Excision Repair Variants and Pesticide Exposure Increase Parkinson's Disease Risk. Toxicol Sci. 2017 Jul 1;158(1):188-198. doi: 10.1093/toxsci/kfx086.
• [19] Cardiac overexpression of 8-oxoguanine DNA glycosylase 1 protects mitochondrial DNA and reduces cardiac fibrosis following transaortic constriction. Am J Physiol Heart Circ Physiol. 2011 Nov;301(5):H2073-80. doi: 10.1152/ajpheart.00157.2011. Epub 2011 Aug 26.