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

General Information of Drug (ID: DM2HU9I)

• Drug Name: Triamterene Drug Info
• Synonyms: Ademin; Ademine; Amteren; Anjal; Dazid; Diarol; Dinazide; Diren; Ditak; Diucelpin; Diurene; Diutensat; Diuteren; Dyberzide; Dyren; Dyrenium; Dytac; Dytenzide; Esiteren; Hidiurese; Hydrene; Hypertorr; Isobar; Jatropur; Jenateren; Kalspare; Masuharmin; Nephral; Noridil; Noridyl; Pterofen; Pterophene; Renezide; Reviten; Taturil; Teriam; Teridin; Triamizide; Triampur; Triamteren; Triamterena; Triamterenum; Triamteril; Triamterine; Triamthiazid; Tricilone; Trispan; Triteren; Triurene; Trizid; Turfa; Uretren; Urocaudal; Goldshield Brand of Triamterene; Jorba Brand of Triamterene; Pter ophene; SmithKline Beecham Brand of Triamterene; TRIAMTERENE USP; Thiazid Wolff; Triamteril complex; Wellspring Brand of Triamterene; Fluss 40; SKF 8542; T 4143; Ademin(e); Apo-triazide; Dyrenium (TN); Pteridine deriv. 11; SALI-PUREN; SK&F 8542; SK-8542; Tri-Span; Triamterena [INN-Spanish]; Triamterenum [INN-Latin]; SK&F-8542; Triamterene (JP15/USP/INN); Triamterene [USAN:INN:BAN:JAN]; 2,4,7-Triamino-6-fenilpteridina; 2,4,7-Triamino-6-fenilpteridina [Italian]; 2,4,7-Triamino-6-phenylpteridine; 6-PHENYL-2,4,7-TRIAMINO PTERIDINE; 6-Phenyl-2,4,7-pteridinetriamine; 6-Phenyl-2,4,7-triaminopteridine; 6-phenylpteridine-2,4,7-triamine

Indication

Disease Entry	ICD 11	Status	REF
Congestive heart failure	BD10	Approved	[1]
Edema	MG29	Approved	[1]
Hypertension	BA00-BA04	Approved	[1]
High blood pressure	BA00	Investigative	[2]

• Therapeutic Class: Diuretics
• Cross-matching ID:
  PubChem CID: 5546
  ChEBI ID: CHEMBL9671
  CAS Number: CAS 396-01-0
  TTD Drug ID: DM2HU9I
  VARIDT Drug ID: DR01341
  INTEDE Drug ID: DR1636
  ACDINA Drug ID: D00700

Molecule-Related Drug Atlas

Drug(s) Targeting Amiloride-sensitive sodium channel (ENaC)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
VX-371	DMSTHG1	Cystic fibrosis	CA25	Phase 2	[6]
benzamil	DM57SVW	Discovery agent	N.A.	Investigative	[7]
S3969	DM84DMW	Discovery agent	N.A.	Investigative	[8]

Drug(s) Transported By Organic cation transporter 1 (SLC22A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[9]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[10]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[11]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[12]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[13]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[14]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[15]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[16]
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[17]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[18]

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
Amiloride-sensitive sodium channel (ENaC)	TTQM7TE	SCNNA_HUMAN; SCNNB_HUMAN; SCNNG_HUMAN; SCNND_HUMAN	Blocker	[3]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[4]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 1A2 (CYP1A2) Main DME	DEJGDUW	CP1A2_HUMAN	Substrate	[5]

References

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• [2] Triamterene FDA Label
• [3] Effects of the serine/threonine kinase SGK1 on the epithelial Na(+) channel (ENaC) and CFTR: implications for cystic fibrosis. Cell Physiol Biochem. 2001;11(4):209-18.
• [4] Identification of novel substrates and structure-activity relationship of cellular uptake mediated by human organic cation transporters 1 and 2. J Med Chem. 2013 Sep 26;56(18):7232-42.
• [5] Rate-limiting biotransformation of triamterene is mediated by CYP1A2. Int J Clin Pharmacol Ther. 2005 Jul;43(7):327-34.
• [6] The in vitro effect of nebulised hypertonic saline on human bronchial epithelium. Eur Respir J. 2018 May 17;51(5):1702652.
• [7] 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. (Target id: 742).
• [8] Small molecule activator of the human epithelial sodium channel. J Biol Chem. 2008 May 2;283(18):11981-94.
• [9] Are organic cation transporters capable of transporting prostaglandins? Naunyn Schmiedebergs Arch Pharmacol. 2005 Aug;372(2):125-30.
• [10] Cisplatin and oxaliplatin, but not carboplatin and nedaplatin, are substrates for human organic cation transporters (SLC22A1-3 and multidrug and toxin extrusion family). J Pharmacol Exp Ther. 2006 Nov;319(2):879-86.
• [11] Pharmacologic markers and predictors of responses to imatinib therapy in patients with chronic myeloid leukemia. Leuk Lymphoma. 2008 Apr;49(4):639-42.
• [12] Organic cation transporters are determinants of oxaliplatin cytotoxicity. Cancer Res. 2006 Sep 1;66(17):8847-57.
• [13] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [14] Implications of genetic polymorphisms in drug transporters for pharmacotherapy. Cancer Lett. 2006 Mar 8;234(1):4-33.
• [15] Upregulation of histone acetylation reverses organic anion transporter 2 repression and enhances 5-fluorouracil sensitivity in hepatocellular carcinoma
• [16] Comparison of type I and type II organic cation transport by organic cation transporters and organic anion-transporting polypeptides. J Pharmacol Exp Ther. 2001 Jul;298(1):110-5.
• [17] Organic cation transporters and their pharmacokinetic and pharmacodynamic consequences. Drug Metab Pharmacokinet. 2008;23(4):243-53.
• [18] Influx Transport of Cationic Drug at the Blood-Retinal Barrier: Impact on the Retinal Delivery of Neuroprotectants. Biol Pharm Bull. 2017;40(8):1139-1145.
• [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.