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

General Information of Drug (ID: DMSZPR3)

• Drug Name: Rolofylline Drug Info
• Synonyms: KW 3902; HMR-4902; KW-3902; MK-7418; Rolofylline (USAN); 1,3-Dipropyl-8-(3-noradamantyl)xanthine; 1,3-Dnax; 8-(3-Noradamantyl)-1,3-dipropylxanthine; 8-(Hexahydro-2,5-methanopentalen-3a(1H)-yl)-3,7-dihydro-1,3-dipropyl-1H-purine-2,6-dione; 8-(Noradamantan-3-yl)-1,3-dipropylxanthine; 8-(hexahydro-2,5-methanopentalen-3a(1h)-yl)-1,3-dipropyl-3,7-dihydro-1h-purine-2,6-dione

Indication

Disease Entry	ICD 11	Status	REF
Heart failure	BD10-BD13	Phase 3	[1]

• Cross-matching ID:
  PubChem CID: 64627
  CAS Number: CAS 136199-02-5
  TTD Drug ID: DMSZPR3
  VARIDT Drug ID: DR00694
  INTEDE Drug ID: DR1907

Molecule-Related Drug Atlas

Drug(s) Targeting Adenosine A1 receptor (ADORA1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Caffeine	DMKBJWP	Allergic rhinitis	CA08.0	Approved	[4]
Tonapofylline	DMBH316	Acute and chronic heart failure	BD1Z	Phase 2	[5]
AMP-579	DMJ4GPR	Hyperlipidaemia	5C80	Phase 2	[6]
SELODENOSON	DMQM3IX	Cardiac arrhythmias	BC9Z	Phase 2	[7]
Apaxifylline	DMQMV9F	Cognitive impairment	6D71	Phase 2	[8]
SLV320	DM867BJ	Heart failure	BD10-BD13	Phase 2	[9]
DTI-0009	DMV84OK	Atrial fibrillation	BC81.3	Phase 2	[7]
Capadenoson	DMYWO62	Atrial fibrillation	BC81.3	Phase 2	[10]
BAY 1067197	DM4JGNH	Heart failure	BD10-BD13	Phase 2	[11]
INO-8875	DMKNA94	Glaucoma/ocular hypertension	9C61	Phase 1/2	[12]

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[13]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[14]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[15]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[16]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[17]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[18]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[19]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[20]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[14]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[21]

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	Antagonist	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[3]

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: 5604).
• [2] Association between the PDE4D gene and ischaemic stroke in the Chinese Han population. Clin Sci (Lond). 2009 Aug 17;117(7):265-72.
• [3] Simultaneous pharmacokinetic model for rolofylline and both M1-trans and M1-cis metabolites. AAPS J. 2013 Apr;15(2):498-504.
• [4] Caffeine as a psychomotor stimulant: mechanism of action. Cell Mol Life Sci. 2004 Apr;61(7-8):857-72.
• [5] 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.
• [6] 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.
• [7] Recent developments in adenosine receptor ligands and their potential as novel drugs. Biochim Biophys Acta. 2011 May;1808(5):1290-308.
• [8] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004779)
• [9] 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.
• [10] A1 adenosine receptor agonists and their potential therapeutic applications. Expert Opin Investig Drugs. 2008 Dec;17(12):1901-10.
• [11] 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.
• [12] INO-8875, a highly selective A1 adenosine receptor agonist: evaluation of chronotropic, dromotropic, and hemodynamic effects in rats. J Pharmacol Exp Ther. 2013 Jan;344(1):59-67.
• [13] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [14] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [15] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [16] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [17] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [18] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [19] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [20] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [21] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.