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

General Information of Drug (ID: DMFGUCY)

• Drug Name: 8-PHENYL THEOPHYLLINE Drug Info
• Synonyms: 8-Phenyltheophylline; 1,3-Dimethyl-8-phenylxanthine; 961-45-5; Theophylline, 8-phenyl-; UNII-E6M543P3BL; NSC 14127; CHEMBL62350; E6M543P3BL; MFCD00005582; 1,3-dimethyl-8-phenyl-3,7-dihydro-1H-purine-2,6-dione; 1,3-dimethyl-8-phenyl-7H-purine-2,6-dione; 1H-Purine-2,6-dione, 2,3,6,7-tetrahydro-1,3-dimethyl-8-phenyl-; AC1L1CIX; Lopac-P-2278; Oprea1_390706; Lopac0_000917; MLS000069624; SCHEMBL516432; 8-PT; 8-Phenyl-1,3-dimethylxanthine; 1,3-dimethyl-8-phenyl-1H-purine-2,6(3H,7H)-dione; BDBM82015; DTXSID90242119; MolPort-002-605-303

Indication

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

• Cross-matching ID:
  PubChem CID: 1922
  CAS Number: CAS 961-45-5
  TTD Drug ID: DMFGUCY

Molecule-Related Drug Atlas

Drug(s) Targeting Adenosine A3 receptor (ADORA3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
IB-MECA	DM9G5XD	Psoriasis vulgaris	EA90	Phase 3	[5]
Tonapofylline	DMBH316	Acute and chronic heart failure	BD1Z	Phase 2	[6]
NITD609	DMQHBSX	Malaria	1F40-1F45	Phase 2	[7]
CF102	DMP56WJ	Hepatocellular carcinoma	2C12.02	Phase 2	[8]
SCH-442416	DMQ2K1V	N. A.	N. A.	Phase 1	[9]
AST-004	DM5WMG7	Stroke	8B20	Phase 1	[10]
BEMESETRON	DMSPJX9	N. A.	N. A.	Discontinued in Phase 3	[11]
BAY 60-6583	DMTEJV1	Myocardial ischemia	BA6Z	Preclinical	[12]
CF602	DM0ULO2	Inflammation	1A00-CA43.1	Preclinical	[8]
CF502	DMQSJ20	Inflammation	1A00-CA43.1	Preclinical	[8]

Drug(s) Targeting Adenosine A2a receptor (ADORA2A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Caffeine	DMKBJWP	Allergic rhinitis	CA08.0	Approved	[13]
Istradefylline	DM20VSK	Parkinson disease	8A00.0	Approved	[14]
Regadenoson	DM76VHG	Radionuclide imaging	N.A.	Approved	[15]
Tozadenant	DMATC14	Parkinson disease	8A00.0	Phase 3	[16]
Binodenoson	DMVHF8G	Hypertension	BA00-BA04	Phase 3	[17]
Apadenoson	DMD8QTC	Coronary artery disease	BA80	Phase 3	[18]
Tonapofylline	DMBH316	Acute and chronic heart failure	BD1Z	Phase 2	[6]
Dexefaroxan	DMTY4KN	Parkinson disease	8A00.0	Phase 2	[19]
AMP-579	DMJ4GPR	Hyperlipidaemia	5C80	Phase 2	[20]
BIIB014	DMH7RJ1	Parkinson disease	8A00.0	Phase 2	[21]

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	[22]
Vidarabine	DM0N85H	Hepatosplenic T-cell lymphoma		Approved	[22]
A295	DM55GO2	Aggressive cancer	2A00-2F9Z	IND submitted	[23]
Tonapofylline	DMBH316	Acute and chronic heart failure	BD1Z	Phase 2	[6]
YT-146	DM3YVKQ	Hypertension	BA00-BA04	Phase 2	[24]
AB928	DMDOXMN	Metastatic colorectal cancer	2B91	Phase 1/2	[25]
KF-17837	DMQ6DLZ	Parkinson disease	8A00.0	Phase 1	[26]
Xanthine	DMFBOQ7	Apnea	MD11.0	Phase 1	[27]
CVT-6883	DMY84TW	Asthma	CA23	Phase 1	[28]
PBF-1129	DMOPGXM	Non-small-cell lung cancer	2C25.Y	Phase 1	[25]

Drug(s) Targeting Adenosine A1 receptor (ADORA1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Caffeine	DMKBJWP	Allergic rhinitis	CA08.0	Approved	[13]
Rolofylline	DMSZPR3	Heart failure	BD10-BD13	Phase 3	[29]
Tonapofylline	DMBH316	Acute and chronic heart failure	BD1Z	Phase 2	[6]
AMP-579	DMJ4GPR	Hyperlipidaemia	5C80	Phase 2	[20]
SELODENOSON	DMQM3IX	Cardiac arrhythmias	BC9Z	Phase 2	[30]
Apaxifylline	DMQMV9F	Cognitive impairment	6D71	Phase 2	[31]
SLV320	DM867BJ	Heart failure	BD10-BD13	Phase 2	[32]
DTI-0009	DMV84OK	Atrial fibrillation	BC81.3	Phase 2	[30]
Capadenoson	DMYWO62	Atrial fibrillation	BC81.3	Phase 2	[33]
BAY 1067197	DM4JGNH	Heart failure	BD10-BD13	Phase 2	[34]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zolmitriptan	DM1IB4Q	Migraine	8A80	Approved	[35]
Rofecoxib	DM3P5DA	Osteoarthritis	FA00-FA05	Approved	[35]
Etoricoxib	DM6A4NW	Rheumatoid arthritis	FA20	Approved	[35]
Capsaicin	DMGMF6V	Back pain	ME84.Z	Approved	[36]
Hesperetin	DMKER83	High blood cholesterol level	5C80.00	Approved	[37]
Stiripentol	DMMSDOY	Dravet syndrome	8A61.11	Approved	[38]
Nifedipine	DMSVOZT	Angina pectoris	BA40	Approved	[39]
Zileuton	DMVRIC2	Allergic asthma	CA23.0	Approved	[40]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[41]
Clonidine	DM6RZ9Q	Attention deficit hyperactivity disorder	6A05.Z	Approved	[42]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Adenosine A1 receptor (ADORA1)	TTK25J1	AA1R_HUMAN	Inhibitor	[1]
Adenosine A2a receptor (ADORA2A)	TTM2AOE	AA2AR_HUMAN	Inhibitor	[1]
Adenosine A2b receptor (ADORA2B)	TTNE7KG	AA2BR_HUMAN	Inhibitor	[2]
Adenosine A3 receptor (ADORA3)	TTJFY5U	AA3R_HUMAN	Inhibitor	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Gene/Protein Processing	[4]

References

• [1] 1H-imidazo[4,5-c]quinolin-4-amines: novel non-xanthine adenosine antagonists. J Med Chem. 1991 Mar;34(3):1202-6.
• [2] 2-Alkynyl-8-aryl-9-methyladenines as novel adenosine receptor antagonists: their synthesis and structure-activity relationships toward hepatic gluc... J Med Chem. 2001 Jan 18;44(2):170-9.
• [3] Adenosine receptors: targets for future drugs. J Med Chem. 1982 Mar;25(3):197-207.
• [4] Inhibition of human CYP1A2 activity in vitro by methylxanthines: potent competitive inhibition by 8-phenyltheophylline. Xenobiotica. 2001 Mar;31(3):135-51.
• [5] A role for central A3-adenosine receptors. Mediation of behavioral depressant effects. FEBS Lett. 1993 Dec 20;336(1):57-60.
• [6] 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.
• [7] Spiroindolones, a potent compound class for the treatment of malaria. Science. 2010 Sep 3;329(5996):1175-80.
• [8] 2011 Pipeline of Can-Fite BioPharm.
• [9] Synthesis and evaluation of 1,2,4-triazolo[1,5-c]pyrimidine derivatives as A2A receptor-selective antagonists. Bioorg Med Chem Lett. 2010 Oct 1;20(19):5690-4.
• [10] Adenosine A1R/A3R (Adenosine A1 and A3 Receptor) Agonist AST-004 Reduces Brain Infarction in a Nonhuman Primate Model of Stroke. Stroke. 2022 Jan;53(1):238-248.
• [11] 2-n-Butyl-9-methyl-8-[1,2,3]triazol-2-yl-9H-purin-6-ylamine and analogues as A2A adenosine receptor antagonists. Design, synthesis, and pharmacolog... J Med Chem. 2005 Nov 3;48(22):6887-96.
• [12] Protein kinase C protects preconditioned rabbit hearts by increasing sensitivity of adenosine A2b-dependent signaling during early reperfusion. J Mol Cell Cardiol. 2007 Sep;43(3):262-71.
• [13] Caffeine as a psychomotor stimulant: mechanism of action. Cell Mol Life Sci. 2004 Apr;61(7-8):857-72.
• [14] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [15] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [16] Tozadenant (SYN115) in patients with Parkinson's disease who have motor fluctuations on levodopa: a phase 2b, double-blind, randomised trial. Lancet Neurol. 2014 Aug;13(8):767-76.
• [17] Coronary circulation responses to binodenoson, a selective adenosine A2A receptor agonist. Am J Cardiol. 2007 Jun 1;99(11):1507-12.
• [18] 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: 3290).
• [19] The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.
• [20] Adenosine A1/A2a receptor agonist AMP-579 induces acute and delayed preconditioning against in vivo myocardial stunning. Am J Physiol Heart Circ Physiol. 2004 Dec;287(6):H2746-53.
• [21] Novel pharmacological targets for the treatment of Parkinson's disease. Nat Rev Drug Discov. 2006 Oct;5(10):845-54.
• [22] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [23] Clinical pipeline report, company report or official report of Klus Pharma
• [24] Identification of adenosine A2 receptor-cAMP system in human aortic endothelial cells. Biochem Biophys Res Commun. 1994 Mar 15;199(2):905-10.
• [25] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [26] 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.
• [27] Role of adenosine in asthma. Drug Dev Res. 1996;39:333-6.
• [28] 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.
• [29] Association between the PDE4D gene and ischaemic stroke in the Chinese Han population. Clin Sci (Lond). 2009 Aug 17;117(7):265-72.
• [30] Recent developments in adenosine receptor ligands and their potential as novel drugs. Biochim Biophys Acta. 2011 May;1808(5):1290-308.
• [31] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004779)
• [32] Role of matrix metalloproteinases and their tissue inhibitors as potential biomarkers of left ventricular remodelling in the athlete's heart. Clin Sci (Lond). 2009 Jul 16;117(4):157-64.
• [33] A1 adenosine receptor agonists and their potential therapeutic applications. Expert Opin Investig Drugs. 2008 Dec;17(12):1901-10.
• [34] Separation of on-target efficacy from adverse effects through rational design of a bitopic adenosine receptor agonist. Current Issue vol. 111 no. 12 Celine Valant, 4614-4619.
• [35] In vitro inhibition of CYP1A2 by model inhibitors, anti-inflammatory analgesics and female sex steroids: predictability of in vivo interactions. Basic Clin Pharmacol Toxicol. 2008 Aug;103(2):157-65.
• [36] Effects of capsaicin and dihydrocapsaicin on human and rat liver microsomal CYP450 enzyme activities in vitro and in vivo. J Asian Nat Prod Res. 2012;14(4):382-95.
• [37] Drug interaction study of flavonoids toward CYP3A4 and their quantitative structure activity relationship (QSAR) analysis for predicting potential effects. Toxicol Lett. 2018 Sep 15;294:27-36.
• [38] Stiripentol. Expert Opin Investig Drugs. 2005 Jul;14(7):905-11.
• [39] Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: prediction of in vivo drug-drug interactions. Eur J Clin Pharmacol. 2000 Feb-Mar;55(11-12):843-52.
• [40] Mechanism-based inhibition of human liver microsomal cytochrome P450 1A2 by zileuton, a 5-lipoxygenase inhibitor. Drug Metab Dispos. 2003 Nov;31(11):1352-60.
• [41] Predictive three-dimensional quantitative structure-activity relationship of cytochrome P450 1A2 inhibitors. J Med Chem. 2005 Jun 2;48(11):3808-15.
• [42] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.