Details of the Drug Combination

General Information of Drug Combination (ID: DCIFERO)

• Drug Combination Name: Triamterene + Oxyphenbutazone
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Triamterene (DM2HU9I): Small molecular drug
  Oxyphenbutazone (DMPZS7U): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 7.69
  Bliss Independence Score: 7.69
  Loewe Additivity Score: 13.78
  LHighest Single Agent (HSA) Score: 13.78

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Triamterene

Disease Entry	ICD 11	Status	REF
Congestive heart failure	BD10	Approved	[2]
Edema	MG29	Approved	[2]
Hypertension	BA00-BA04	Approved	[2]
High blood pressure	BA00	Investigative	[3]

Triamterene Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Amiloride-sensitive sodium channel (ENaC)	TTQM7TE	SCNNA_HUMAN; SCNNB_HUMAN; SCNNG_HUMAN; SCNND_HUMAN	Blocker	[5]

Triamterene Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[6]

Triamterene Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[7]

Triamterene Interacts with 4 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Increases Hydroxylation	[7]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Activity	[8]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Affects Activity	[9]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Affects Response To Substance	[10]

Indication(s) of Oxyphenbutazone

Disease Entry	ICD 11	Status	REF
Arthritis	FA20	Approved	[4]

Oxyphenbutazone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Serum albumin (ALB)	TTFNGC9	ALBU_HUMAN	Modulator	[11]

Oxyphenbutazone Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Heat shock factor protein 1 (HSF1)	OTYNJ4KP	HSF1_HUMAN	Increases Activity	[12]

References

• [1] Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
• [2] 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: 4329).
• [3] Triamterene FDA Label
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [5] 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.
• [6] 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.
• [7] Rate-limiting biotransformation of triamterene is mediated by CYP1A2. Int J Clin Pharmacol Ther. 2005 Jul;43(7):327-34.
• [8] Identification of chemical compounds that induce HIF-1alpha activity. Toxicol Sci. 2009 Nov;112(1):153-63.
• [9] Identification of environmental chemicals that activate p53 signaling after in vitro metabolic activation. Arch Toxicol. 2022 Jul;96(7):1975-1987. doi: 10.1007/s00204-022-03291-5. Epub 2022 Apr 18.
• [10] Population-based in vitro hazard and concentration-response assessment of chemicals: the 1000 genomes high-throughput screening study. Environ Health Perspect. 2015 May;123(5):458-66. doi: 10.1289/ehp.1408775. Epub 2015 Jan 13.
• [11] Effect of albumin conformation on binding of phenylbutazone and oxyphenbutazone to human serum albumin. J Pharm Sci. 1982 Feb;71(2):241-4.
• [12] A Gene Expression Biomarker Predicts Heat Shock Factor 1 Activation in a Gene Expression Compendium. Chem Res Toxicol. 2021 Jul 19;34(7):1721-1737. doi: 10.1021/acs.chemrestox.0c00510. Epub 2021 Jun 25.