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

General Information of Drug (ID: DMLHSE3)

• Drug Name: Oxtriphylline Drug Info
• Synonyms: Choledyl; Cholegyl; Cholinophyllin; Cholinophylline; Filoral; Oxtrimethylline; Sabidal; Soliphylline; Teofilcolina; Teokolin; Theoxylline; Choline theophylline salt; Cholini theophyllinas; Colina teofillinato; Colina teofillinato [DCIT]; Oxtriphylline [USAN]; Oxtriphylline pediatric; Teofilinato de colina; Theophyllinate de choline; Theophylline cholinate; Theophylline salt of choline; Choledyl SA 400; Zy 15061; Choledyl (TN); Cholini theophyllinas [INN-Latin]; Teofilinato de colina [INN-Spanish]; Theophyllinate de choline[INN-French]; Choline salt with theophylline (1:1); Theophylline, compd. with choline; Choline, compd. with theophylline (1:1); Choline, hydroxide, compd. with theophylline (1:1); Ethanaminium, 2-hydroxy-N,N,N-trimethyl-, salt with 3,7-dihydro-1,3-dimethylpurine-2,6-dione; Ethanaminium, 2-hydroxy-N,N,N-trimethyl-, salt with 3,7-dihydro-1,3-dimethyl-1H-purine-2,6-dione; Ethanaminium, 2-hydroxy-N,N,N-trimethyl-, salt with 3,7-dihydro-1,3-dimethyl-1H-purine-2,6-dione (1:1); (2-Hydroxyethyl)trimethylammonium compound with theophylline; 1,3-dimethyl-7H-purine-2,6-dione; 1H-Purine-2,6-dione, 3,7-dihydro-1,3-dimethyl-, ion(1-), 2-hydroxy-N,N,N-trimethylethanaminium

Indication

Disease Entry	ICD 11	Status	REF
Cough	MD12	Approved	[1]

• Therapeutic Class: Bronchodilator Agents
• Cross-matching ID:
  PubChem CID: 656652
  CAS Number: CAS 4499-40-5
  TTD Drug ID: DMLHSE3
  INTEDE Drug ID: DR1217

Molecule-Related Drug Atlas

Drug(s) Targeting Phosphodiesterase 3 (PDE3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cilostazol	DMZMSCT	Intermittent claudication	BD40.00	Approved	[2]
Ibudilast	DM4LSPN	Castleman's disease	4B2Y	Approved	[4]
Enoximone	DMQVZJD	Congestive heart failure	BD10	Approved	[5]
Olprinone	DMWBQKU	Heart failure	BD10-BD13	Approved	[6]
Inamrinone Lactate	DMRMFP4	Cardiac disease	BA00-BE2Z	Approved	[7]
Milrinone	DM8TUPF	Congestive heart failure	BD10	Approved	[2]
Tofisopam	DMTGNWU	Hyperuricaemia	5C55.Y	Phase 2	[8]
Tipelukast	DMS9BDQ	Asthma	CA23	Phase 2	[9]
RPL-554	DMLD4VQ	Allergic rhinitis	CA08.0	Phase 2	[10]
Org-30029	DMDZ4R2	Heart failure	BD10-BD13	Phase 2	[11]

Drug(s) Targeting Phosphodiesterase 4 (PDE4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Apremilast	DMTWS9E	Psoriasis vulgaris	EA90	Approved	[12]
Roflumilast	DMPGHY8	Asthma	CA23	Approved	[13]
Ibudilast	DM4LSPN	Castleman's disease	4B2Y	Approved	[4]
crisaborole	DMNVKU6	Atopic dermatitis	EA80	Approved	[14]
Arofylline	DM84AD1	Chronic obstructive pulmonary disease	CA22	Phase 3	[15]
ARQ-151	DML61S4	Atopic dermatitis	EA80	Phase 3	[16]
SUN13834	DMPK34E	Gram-positive bacterial infection	1B74-1G40	Phase 2	[17]
ONO-6126	DMRT28X	Chronic obstructive pulmonary disease	CA22	Phase 2	[15]
E6005	DM1S489	Atopic dermatitis	EA80	Phase 2	[18]
IC-485	DMB1UYV	Chronic obstructive pulmonary disease	CA22	Phase 2	[15]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[19]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[20]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[21]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[22]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[23]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[24]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[25]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[26]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[27]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[28]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Phosphodiesterase 3 (PDE3)	TTZCG4L	NOUNIPROTAC	Modulator	[2]
Phosphodiesterase 4 (PDE4)	TTV5CGO	NOUNIPROTAC	Modulator	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 1A2 (CYP1A2) Main DME	DEJGDUW	CP1A2_HUMAN	Substrate	[3]

References

• [1] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 086742.
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
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• [6] Olprinone: a phosphodiesterase III inhibitor with positive inotropic and vasodilator effects. Cardiovasc Drug Rev. 2002 Fall;20(3):163-74.
• [7] Effects of amrinone on hepatic ischemia-reperfusion injury in rats. J Hepatol. 2002 Jul;37(1):31-8.
• [8] The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis. J Neural Transm (Vienna). 2010 Nov;117(11):1319-25.
• [9] Company report (MediciNova)
• [10] Efficacy and safety of RPL554, a dual PDE3 and PDE4 inhibitor, in healthy volunteers and in patients with asthma or chronic obstructive pulmonary disease: findings from four clinical trials.Lancet Respir Med.2013 Nov;1(9):714-27.
• [11] Effects of the positive inotropic agent Org 30029 on developed force and aequorin light transients in intact canine ventricular myocardium. Circ Res. 1993 Mar;72(3):597-606.
• [12] Highly selective phosphodiesterase 4 inhibitors for the treatment of allergic skin diseases and psoriasis. Inflamm Allergy Drug Targets. 2007 Mar;6(1):17-26.
• [13] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [14] 2016 FDA drug approvals. Nat Rev Drug Discov. 2017 Feb 2;16(2):73-76.
• [15] Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.
• [16] Trial of Roflumilast Cream for Chronic Plaque Psoriasis. N Engl J Med. 2020 Jul 16;383(3):229-239.
• [17] Ocular hypotension induced by topical dopaminergic drugs and phosphodiesterase inhibitors. Eur J Pharmacol. 1994 Jun 2;258(1-2):85-94.
• [18] Antipruritic effect of the topical phosphodiesterase 4 inhibitor E6005 ameliorates skin lesions in a mouse atopic dermatitis model. J Pharmacol Exp Ther. 2013 Jul;346(1):105-12.
• [19] 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.
• [20] 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.
• [21] Endoxifen and other metabolites of tamoxifen inhibit human hydroxysteroid sulfotransferase 2A1 (hSULT2A1). Drug Metab Dispos. 2014 Nov;42(11):1843-50.
• [22] Cytochrome P450 1A2 (CYP1A2) activity and risk factors for breast cancer: a cross-sectional study. Breast Cancer Res. 2004;6(4):R352-65.
• [23] PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics. 2015 Aug;25(8):416-26.
• [24] The effect of apigenin on pharmacokinetics of imatinib and its metabolite N-desmethyl imatinib in rats. Biomed Res Int. 2013;2013:789184.
• [25] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [26] 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.
• [27] Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1993 Sep;348(3):332-7.
• [28] Metabolism and metabolic inhibition of xanthotoxol in human liver microsomes. Evid Based Complement Alternat Med. 2016;2016:5416509.