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

General Information of Drug (ID: DMFBOQ7)

• Drug Name: Xanthine Drug Info
• Synonyms: xanthine; 69-89-6; 2,6-Dihydroxypurine; Xanthin; 2,6-dioxopurine; Pseudoxanthine; Isoxanthine; 1H-Purine-2,6(3H,7H)-dione; Xanthic oxide; 1H-Purine-2,6-diol; 9H-Purine-2,6-diol; Purine-2,6-diol; 3,7-Dihydro-1H-purine-2,6-dione; 2,6(1,3)-Purinedion; 1H-Purine-2,6-dione, 3,7-dihydro-; 3,7-dihydropurine-2,6-dione; USAF CB-17; XAN; Purine-2(3H),6(1H)-dione; 2,6-Dioxo-1,2,3,6-tetrahydropurine; 3,9-dihydro-1H-purine-2,6-dione; 9H-Purine-2,6-(1H,3H)-dione; 1H-Purine-2,6-dione, 3,9-dihydro-; Purine-2,6-(1H,3H)-dione; 9H-xanthine

Indication

Disease Entry	ICD 11	Status	REF
Apnea	MD11.0	Phase 1	[1]

• Cross-matching ID:
  PubChem CID: 1188
  ChEBI ID: CHEBI:17712
  CAS Number: CAS 69-89-6
  TTD Drug ID: DMFBOQ7
  INTEDE Drug ID: DR1719

Molecule-Related Drug Atlas

Drug(s) Targeting Adenosine A2b receptor (ADORA2B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Adenosine	DMM2NSK	Paroxysmal supraventricular tachycardia	BC81.Z	Approved	[6]
Vidarabine	DM0N85H	Hepatosplenic T-cell lymphoma		Approved	[6]
A295	DM55GO2	Aggressive cancer	2A00-2F9Z	IND submitted	[7]
Tonapofylline	DMBH316	Acute and chronic heart failure	BD1Z	Phase 2	[8]
YT-146	DM3YVKQ	Hypertension	BA00-BA04	Phase 2	[9]
AB928	DMDOXMN	Metastatic colorectal cancer	2B91	Phase 1/2	[10]
KF-17837	DMQ6DLZ	Parkinson disease	8A00.0	Phase 1	[11]
CVT-6883	DMY84TW	Asthma	CA23	Phase 1	[12]
PBF-1129	DMOPGXM	Non-small-cell lung cancer	2C25.Y	Phase 1	[10]
PF-1913539	DMXEU14	Alzheimer disease	8A20	Discontinued in Phase 3	[13]

Drug(s) Metabolized By Cytochrome P450 1A2 (CYP1A2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[14]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[15]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[16]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[17]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[18]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[19]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[20]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[21]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[22]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[23]

Drug(s) Metabolized By Xanthine dehydrogenase/oxidase (XDH)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[24]

Drug(s) Affected By Aldehyde dehydrogenase 1A1 (ALDH1A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[25]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[26]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[27]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[28]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[29]
Cyclophosphamide	DM4O2Z7	Advanced cancer	2A00-2F9Z	Approved	[30]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[31]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[32]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[33]
Disulfiram	DMCL2OK	Alcohol dependence	6C40.2	Approved	[34]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Adenosine A2b receptor (ADORA2B)	TTNE7KG	AA2BR_HUMAN	Antagonist	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Substrate	[3]
Xanthine dehydrogenase/oxidase (XDH)	DECG04O	XDH_HUMAN	Substrate	[4]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Aldehyde dehydrogenase 1A1 (ALDH1A1)	OTCUWZKB	AL1A1_HUMAN	Gene/Protein Processing	[5]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4557).
• [2] Role of adenosine in asthma. Drug Dev Res. 1996;39:333-6.
• [3] Rapid determination of five probe drugs and their metabolites in human plasma and urine by liquid chromatography/tandem mass spectrometry: application to cytochrome P450 phenotyping studies. Rapid Commun Mass Spectrom. 2004;18(23):2921-33.
• [4] Molecular characterization and taurine regulation of two novel CDOs (CDO1 and CDO2) from Carassius auratus. Comp Biochem Physiol B Biochem Mol Biol. 2019 Sep;235:54-61.
• [5] Development of a high-throughput in vitro assay to identify selective inhibitors for human ALDH1A1. Chem Biol Interact. 2015 Jun 5;234:29-37.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [7] Clinical pipeline report, company report or official report of Klus Pharma
• [8] 2-Amino-5-benzoyl-4-phenylthiazoles: Development of potent and selective adenosine A1 receptor antagonists. Bioorg Med Chem. 2010 Mar 15;18(6):2195-2203.
• [9] Identification of adenosine A2 receptor-cAMP system in human aortic endothelial cells. Biochem Biophys Res Commun. 1994 Mar 15;199(2):905-10.
• [10] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [11] Photoisomerization of a potent and selective adenosine A2 antagonist, (E)-1,3-Dipropyl-8-(3,4-dimethoxystyryl)-7-methylxanthine. J Med Chem. 1993 Nov 12;36(23):3731-3.
• [12] GS-6201, a selective blocker of the A2B adenosine receptor, attenuates cardiac remodeling after acute myocardial infarction in the mouse. J Pharmacol Exp Ther. 2012 Dec;343(3):587-95.
• [13] Differences in the order of potency for agonists but not antagonists at human and rat adenosine A2A receptors. Biochem Pharmacol. 1999 Jan 1;57(1):65-75.
• [14] Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos. 2000 Dec;28(12):1457-63.
• [15] Effects of polyunsaturated fatty acids on prostaglandin synthesis and cyclooxygenase-mediated DNA adduct formation by heterocyclic aromatic amines in human adenocarcinoma colon cells. Mol Carcinog. 2004 Jul;40(3):180-8.
• [16] Endoxifen and other metabolites of tamoxifen inhibit human hydroxysteroid sulfotransferase 2A1 (hSULT2A1). Drug Metab Dispos. 2014 Nov;42(11):1843-50.
• [17] Cytochrome P450 1A2 (CYP1A2) activity and risk factors for breast cancer: a cross-sectional study. Breast Cancer Res. 2004;6(4):R352-65.
• [18] PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics. 2015 Aug;25(8):416-26.
• [19] The effect of apigenin on pharmacokinetics of imatinib and its metabolite N-desmethyl imatinib in rats. Biomed Res Int. 2013;2013:789184.
• [20] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [21] The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentrations in Chinese coke oven workers. Sci Total Environ. 2007 Aug 1;381(1-3):38-46.
• [22] Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1993 Sep;348(3):332-7.
• [23] Metabolism and metabolic inhibition of xanthotoxol in human liver microsomes. Evid Based Complement Alternat Med. 2016;2016:5416509.
• [24] Xanthine oxidoreductase in drug metabolism: beyond a role as a detoxifying enzyme. Curr Med Chem. 2016;23(35):4027-4036.
• [25] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [26] Ciprofloxacin mediates cancer stem cell phenotypes in lung cancer cells through caveolin-1-dependent mechanism. Chem Biol Interact. 2016 Apr 25;250:1-11.
• [27] Methotrexate modulates folate phenotype and inflammatory profile in EA.hy 926 cells. Eur J Pharmacol. 2014 Jun 5;732:60-7.
• [28] 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.
• [29] RNAi-mediated knockdown of aldehyde dehydrogenase class-1A1 and class-3A1 is specific and reveals that each contributes equally to the resistance against 4-hydroperoxycyclophosphamide. Cancer Chemother Pharmacol. 2007 Jan;59(1):127-36. doi: 10.1007/s00280-006-0233-6. Epub 2006 Apr 14.
• [30] Comparative gene expression analysis of a chronic myelogenous leukemia cell line resistant to cyclophosphamide using oligonucleotide arrays and response to tyrosine kinase inhibitors. Leuk Res. 2007 Nov;31(11):1511-20.
• [31] A comprehensive analysis of Wnt/beta-catenin signaling pathway-related genes and crosstalk pathways in the treatment of As2O3 in renal cancer. Ren Fail. 2018 Nov;40(1):331-339.
• [32] Inhibition of aldehyde dehydrogenase-1 and p-glycoprotein-mediated multidrug resistance by curcumin and vitamin D3 increases sensitivity to paclitaxel in breast cancer. Chem Biol Interact. 2020 Jan 5;315:108865. doi: 10.1016/j.cbi.2019.108865. Epub 2019 Oct 16.
• [33] 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.
• [34] The interaction of disulfiram and H(2)S metabolism in inhibition of aldehyde dehydrogenase activity and liver cancer cell growth. Toxicol Appl Pharmacol. 2021 Sep 1;426:115642. doi: 10.1016/j.taap.2021.115642. Epub 2021 Jul 6.