Details of the Drug Combination

General Information of Drug Combination (ID: DCJBGND)

• Drug Combination Name: Triamterene + Ginsenoside Rb1
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Triamterene (DM2HU9I): Small molecular drug
  Ginsenoside Rb1 (DMF70AB): N.A.
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 9.19
  Bliss Independence Score: 9.19
  Loewe Additivity Score: 22.18
  LHighest Single Agent (HSA) Score: 22.2

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	[4]

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	[5]

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	[6]

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	[6]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Activity	[7]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Affects Activity	[8]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Affects Response To Substance	[9]

Ginsenoside Rb1 Interacts with 23 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Beta-glucosidase (bglA)	DEUO7V8	A0A509DD13_9STRE	Metabolism	[10]
Beta-glucosidase (bglA)	DE4LKZ9	A0A3D1ZWL4_9BIFI	Metabolism	[10]
Beta-glucosidase (bglA)	DEM6GYO	A0A351PC96_9FIRM	Metabolism	[11], [10]
Beta-glucosidase (bglA)	DE9N4OU	C6WCL5_ACTMD	Metabolism	[12]
Beta-glucosidase (bglA)	DERPJZ6	A0A4Q4LS82_BIFAN	Metabolism	[13]
Beta-glucosidase (bglA)	DEVLXCG	R7LVY8_9FUSO	Metabolism	[10]
Beta-glucosidase (bglA)	DEUQTKA	A0A249DCH3_LACRH	Metabolism	[13]
Beta-glucosidase (bglA)	DEXRUS1	A0A267WL33_9BIFI	Metabolism	[14]
Beta-glucosidase (bglA)	DERX7ML	A0A3B8TKP6_9FIRM	Metabolism	[14]
Beta-glucosidase (bglA)	DEOHI3U	A0A0P0FEZ9_BACT4	Metabolism	[14]
Beta-glucosidase (bglA)	DE46IH1	A0A1T4QCU7_9PROT	Metabolism	[15]
Beta-glucosidase (bglA)	DEE8WXK	A0A076JJU4_BIFAD	Metabolism	[14]
Beta-glucosidase (bglA)	DECBSVP	A0A126SWK8_9BIFI	Metabolism	[14]
Beta-glucosidase (bglA)	DEAVLU4	BGLFU_BIFBR	Metabolism	[14]
Beta-glucosidase (bglA)	DEPBQES	BGLS_BUTFI	Metabolism	[14]
Beta-glucosidase (bglA)	DEGVUWH	A0A174JG46_9FIRM	Metabolism	[14]
Beta-glucosidase (bglA)	DEE8RS0	A0A174GPV4_9FIRM	Metabolism	[14]
Beta-glucosidase (bglA)	DEC0M8H	A0A174ZK85_9FIRM	Metabolism	[14]
Beta-glucosidase (bglA)	DE2OMS0	A0A173UNF6_9FIRM	Metabolism	[14]
Beta-glucosidase (bglA)	DEPUNVR	A0A395V8H8_9FIRM	Metabolism	[14]
Beta-glucosidase (bglA)	DEX7SAW	A0A3R6A2W5_9FIRM	Metabolism	[14]
Beta-glucosidase (bglA)	DEE3I1P	A0A412BAD0_9FIRM	Metabolism	[14]
Beta-glucosidase (bglA)	DEASJG5	A5ZMW4_9FIRM	Metabolism	[14]

Ginsenoside Rb1 Interacts with 7 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Progesterone receptor (PGR)	OT0FZ3QE	PRGR_HUMAN	Increases Expression	[16]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[17]
Potassium voltage-gated channel subfamily E member 1 (KCNE1)	OTZNQUW9	KCNE1_HUMAN	Increases Expression	[18]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Increases Phosphorylation	[17]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Affects Activity	[19]
Sequestosome-1 (SQSTM1)	OTGY5D5J	SQSTM_HUMAN	Decreases Expression	[20]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Increases Expression	[21]

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] 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.
• [5] 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.
• [6] Rate-limiting biotransformation of triamterene is mediated by CYP1A2. Int J Clin Pharmacol Ther. 2005 Jul;43(7):327-34.
• [7] Identification of chemical compounds that induce HIF-1alpha activity. Toxicol Sci. 2009 Nov;112(1):153-63.
• [8] 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.
• [9] 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.
• [10] Constitutive beta-glucosidases hydrolyzing ginsenoside Rb1 and Rb2 from human intestinal bacteria. Biol Pharm Bull. 2000 Dec;23(12):1481-5.
• [11] Intestinal bacterial hydrolysis is required for the appearance of compound K in rat plasma after oral administration of ginsenoside Rb1 from Panax ginseng. J Pharm Pharmacol. 1998 Oct;50(10):1155-60.
• [12] Characterization of the ginsenoside-transforming recombinant beta-glucosidase from Actinosynnema mirum and bioconversion of major ginsenosides into minor ginsenosides. Appl Microbiol Biotechnol. 2013 Jan;97(2):649-59.
• [13] Fermentation of protopanaxadiol type ginsenosides (PD) with probiotic Bifidobacterium lactis and Lactobacillus rhamnosus. Appl Microbiol Biotechnol. 2017 Jul;101(13):5427-5437.
• [14] Developing a metagenomic view of xenobiotic metabolism. Pharmacol Res. 2013 Mar;69(1):21-31.
• [15] Genus Enhydrobacter Staley et al. 1987 should be recognized as a member of the family Rhodospirillaceae within the class Alphaproteobacteria. Microbiol Immunol. 2012 Jan;56(1):21-6.
• [16] Metabolism of ginsenoside Re by human intestinal microflora and its estrogenic effect. Biol Pharm Bull. 2005 Oct;28(10):1903-8. doi: 10.1248/bpb.28.1903.
• [17] Ginsenoside Rb1 protects against 6-hydroxydopamine-induced oxidative stress by increasing heme oxygenase-1 expression through an estrogen receptor-related PI3K/Akt/Nrf2-dependent pathway in human dopaminergic cells. Toxicol Appl Pharmacol. 2010 Jan 1;242(1):18-28. doi: 10.1016/j.taap.2009.09.009. Epub 2009 Sep 23.
• [18] Ginsenosides may enhance the functionality of human embryonic stem cell-derived cardiomyocytes in vitro. Reprod Sci. 2014 Oct;21(10):1312-8. doi: 10.1177/1933719114525269. Epub 2014 Mar 10.
• [19] Modulating effect of ginseng saponins on heterologously expressed HERG currents in Xenopus oocytes. Acta Pharmacol Sin. 2005 May;26(5):551-8. doi: 10.1111/j.1745-7254.2005.00116.x.
• [20] Ginsenoside Rb1 alleviates liver injury induced by 3-chloro-1,2-propanediol by stimulating autophagic flux. J Food Sci. 2021 Dec;86(12):5503-5515. doi: 10.1111/1750-3841.15968. Epub 2021 Nov 23.
• [21] Pharmacodynamics of ginsenosides: antioxidant activities, activation of Nrf2, and potential synergistic effects of combinations. Chem Res Toxicol. 2012 Aug 20;25(8):1574-80. doi: 10.1021/tx2005025. Epub 2012 Aug 9.