Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMT9BPN)

• Drug Name: 8-hydroxyguanine Drug Info

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 135420630
  ChEBI ID: CHEBI:52617
  CAS Number: CAS 5614-64-2
  TTD Drug ID: DMT9BPN

Molecule-Related Drug Atlas

Drug(s) Targeting GTP cyclohydrolase-I (GCH1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Guanine	DMIWLJE	N. A.	N. A.	Phase 3	[1]
ProSavin	DMJ42E6	Parkinson disease	8A00.0	Phase 1/2	[5]
OXB-102	DMXF9DM	Parkinson disease	8A00.0	Phase 1/2	[6]
2-Propanol, Isopropanol	DML5O0H	Discovery agent	N.A.	Investigative	[7]
Guanosine-5'-Triphosphate	DMV2OJX	Discovery agent	N.A.	Investigative	[8]

Drug(s) Affected By N-glycosylase/DNA lyase (OGG1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[9]
Selenium	DM25CGV	N. A.	N. A.	Approved	[10]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[9]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[11]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[12]
Ethanol	DMDRQZU	Chronic pain	MG30	Approved	[13]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[14]
Paclitaxel	DMLB81S	Breast carcinoma		Approved	[15]
Decitabine	DMQL8XJ	Acute myelogenous leukaemia	2A41	Approved	[16]
Menadione	DMSJDTY	Vitamin K deficiency	5B59	Approved	[17]

Drug(s) Affected By Metallothionein-3 (MT3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Quercetin	DM3NC4M	Obesity	5B81	Approved	[18]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[11]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[19]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[20]
Gallium nitrate	DMF9O6B	Hypercalcaemia	5B91.0	Approved	[21]
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[22]
Decitabine	DMQL8XJ	Acute myelogenous leukaemia	2A41	Approved	[23]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[24]
Arsenic	DMTL2Y1	N. A.	N. A.	Approved	[25]
Triclosan	DMZUR4N	Malaria	1F40-1F45	Approved	[26]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
GTP cyclohydrolase-I (GCH1)	TTLSWP6	GCH1_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN	OT81JS6K	WRN_HUMAN	Drug Response	[2]
Metallothionein-3 (MT3)	OTVCZ7HI	MT3_HUMAN	Regulation of Drug Effects	[3]
N-glycosylase/DNA lyase (OGG1)	OTJ97TF3	OGG1_HUMAN	Regulation of Drug Effects	[4]

References

• [1] GTP cyclohydrolase I feedback regulatory protein-dependent and -independent inhibitors of GTP cyclohydrolase I. Arch Biochem Biophys. 2001 Apr 1;388(1):67-73.
• [2] Action-at-a-distance mutagenesis induced by oxidized guanine in Werner syndrome protein-reduced human cells. Chem Res Toxicol. 2015 Apr 20;28(4):621-8. doi: 10.1021/tx500418m. Epub 2015 Mar 2.
• [3] Metallothionein-III prevents gamma-ray-induced 8-oxoguanine accumulation in normal and hOGG1-depleted cells. J Biol Chem. 2004 Aug 13;279(33):34138-49. doi: 10.1074/jbc.M402530200. Epub 2004 Jun 8.
• [4] 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.
• [5] Clinical pipeline report, company report or official report of Oxford BioMedica.
• [6] Clinical pipeline report, company report or official report of Oxford BioMedica.
• [7] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [8] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
• [18] Quercetin reduces oxidative damage induced by paraquat via modulating expression of antioxidant genes in A549 cells. J Appl Toxicol. 2013 Dec;33(12):1460-7. doi: 10.1002/jat.2812. Epub 2012 Sep 20.
• [19] Arsenic trioxide (ATO) influences the gene expression of metallothioneins in human glioblastoma cells. Biol Trace Elem Res. 2012 Dec;149(3):331-9.
• [20] 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.
• [21] Role of oxidative stress in the induction of metallothionein-2A and heme oxygenase-1 gene expression by the antineoplastic agent gallium nitrate in human lymphoma cells. Free Radic Biol Med. 2008 Sep 15;45(6):763-72.
• [22] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [23] Absence of Metallothionein 3 Expression in Breast Cancer is a Rare, But Favorable Marker of Outcome that is Under Epigenetic Control. Toxicol Environ Chem. 2010 Oct;92(9):1673-1695. doi: 10.1080/02772241003711274.
• [24] Altered ErbB receptor signaling and gene expression in cisplatin-resistant ovarian cancer. Cancer Res. 2005 Aug 1;65(15):6789-800. doi: 10.1158/0008-5472.CAN-04-2684.
• [25] Metallothionein 3: an androgen-upregulated gene enhances cell invasion and tumorigenesis of prostate carcinoma cells. Prostate. 2013 Oct;73(14):1495-506. doi: 10.1002/pros.22697. Epub 2013 Jun 21.
• [26] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.