General Information of Drug Combination (ID: DCD65RT)

Drug Combination Name
Atenolol Triamterene
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Atenolol   DMNKG1Z Triamterene   DM2HU9I
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 19.72
Bliss Independence Score: 19.72
Loewe Additivity Score: 33.63
LHighest Single Agent (HSA) Score: 33.65

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Atenolol
Disease Entry ICD 11 Status REF
Angina pectoris BA40 Approved [2]
Hypertension BA00-BA04 Approved [3]
Malignant essential hypertension BA00 Approved [2]
Myocardial infarction BA41-BA43 Approved [2]
Atenolol Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Adrenergic receptor beta-1 (ADRB1) TTR6W5O ADRB1_HUMAN Antagonist [7]
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Atenolol Interacts with 3 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [8]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [9]
Organic anion transporting polypeptide 1A2 (SLCO1A2) DTE2B1D SO1A2_HUMAN Substrate [10]
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Atenolol Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [11]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [12]
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Atenolol Interacts with 27 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Increases ADR [13]
Potassium voltage-gated channel subfamily KQT member 1 (KCNQ1) OT8SPJNX KCNQ1_HUMAN Affects Response To Substance [14]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [15]
Renin (REN) OT52GZR2 RENI_HUMAN Decreases Activity [16]
Angiotensinogen (AGT) OTBZLYR3 ANGT_HUMAN Decreases Expression [17]
Natriuretic peptides A (NPPA) OTMQNTNX ANF_HUMAN Decreases Expression [18]
Apolipoprotein A-I (APOA1) OT5THARI APOA1_HUMAN Decreases Expression [19]
Apolipoprotein A-II (APOA2) OTQ3HGTC APOA2_HUMAN Decreases Expression [19]
Apolipoprotein B-100 (APOB) OTH0UOCZ APOB_HUMAN Increases Expression [19]
Beta-2 adrenergic receptor (ADRB2) OTSDOX4Q ADRB2_HUMAN Increases Expression [20]
Natriuretic peptides B (NPPB) OTSN2IPY ANFB_HUMAN Increases Expression [21]
Reduced folate transporter (SLC19A1) OTWB0BTO S19A1_HUMAN Decreases Expression [22]
Sodium- and chloride-dependent creatine transporter 1 (SLC6A8) OT88C8JA SC6A8_HUMAN Decreases Expression [6]
Beta-2-microglobulin (B2M) OTDWN6NX B2MG_HUMAN Decreases Expression [23]
Small nuclear ribonucleoprotein-associated protein N (SNRPN) OTQB1ID1 RSMN_HUMAN Increases Expression [6]
Peptidyl-prolyl cis-trans isomerase FKBP5 (FKBP5) OT404F9K FKBP5_HUMAN Decreases Expression [6]
Solute carrier organic anion transporter family member 4C1 (SLCO4C1) OTVILUUN SO4C1_HUMAN Increases Expression [6]
C-type lectin domain family 2 member B (CLEC2B) OT0W0M0L CLC2B_HUMAN Increases Expression [6]
Ryanodine receptor 2 (RYR2) OT0PF19E RYR2_HUMAN Increases Activity [24]
Inward rectifier potassium channel 2 (KCNJ2) OT2OQEZS KCNJ2_HUMAN Affects Response To Substance [14]
Voltage-dependent L-type calcium channel subunit alpha-1C (CACNA1C) OT6KFNMS CAC1C_HUMAN Increases Response To Substance [25]
Sodium channel protein type 5 subunit alpha (SCN5A) OTGYZWR6 SCN5A_HUMAN Increases ADR [13]
B2 bradykinin receptor (BDKRB2) OTOA9D3W BKRB2_HUMAN Affects Response To Substance [26]
Endothelin-1 (EDN1) OTZCACEG EDN1_HUMAN Affects Response To Substance [27]
Alpha-2A adrenergic receptor (ADRA2A) OTZFGOTP ADA2A_HUMAN Affects Response To Substance [28]
Potassium voltage-gated channel subfamily E member 1 (KCNE1) OTZNQUW9 KCNE1_HUMAN Increases ADR [13]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Increases ADR [13]
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⏷ Show the Full List of 27 DOT(s)
Indication(s) of Triamterene
Disease Entry ICD 11 Status REF
Congestive heart failure BD10 Approved [4]
Edema MG29 Approved [4]
Hypertension BA00-BA04 Approved [4]
High blood pressure BA00 Investigative [5]
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 [29]
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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 [9]
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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 [30]
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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 [30]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Increases Activity [31]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Affects Activity [32]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Affects Response To Substance [33]
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References

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2 Atenolol FDA Label
3 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: 548).
4 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).
5 Triamterene FDA Label
6 Change in mRNA Expression after Atenolol, a Beta-adrenergic Receptor Antagonist and Association with Pharmacological Response. Arch Drug Inf. 2009 Sep;2(3):41-50. doi: 10.1111/j.1753-5174.2009.00020.x.
7 Prediction and experimental validation of acute toxicity of beta-blockers in Ceriodaphnia dubia. Environ Toxicol Chem. 2005 Oct;24(10):2470-6.
8 Interaction of digoxin with antihypertensive drugs via MDR1. Life Sci. 2002 Feb 15;70(13):1491-500.
9 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.
10 Fruit juice inhibition of uptake transport: a new type of food-drug interaction. Br J Clin Pharmacol. 2010 Nov;70(5):645-55.
11 Metabolism of atenolol in man. Xenobiotica. 1978 May;8(5):313-20.
12 Application of substrate depletion assay to evaluation of CYP isoforms responsible for stereoselective metabolism of carvedilol. Drug Metab Pharmacokinet. 2016 Dec;31(6):425-432.
13 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
14 Additional gene variants reduce effectiveness of beta-blockers in the LQT1 form of long QT syndrome. J Cardiovasc Electrophysiol. 2004 Feb;15(2):190-9. doi: 10.1046/j.1540-8167.2004.03212.x.
15 Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43.
16 Effects of the direct renin inhibitor aliskiren and atenolol alone or in combination in patients with hypertension. J Renin Angiotensin Aldosterone Syst. 2008 Sep;9(3):163-75. doi: 10.1177/1470320308096411.
17 Long-term effects of irbesartan and atenolol on the renin-angiotensin-aldosterone system in human primary hypertension: the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA). J Cardiovasc Pharmacol. 2003 Dec;42(6):719-26. doi: 10.1097/00005344-200312000-00005.
18 Atenolol improves ventricular function without changing plasma noradrenaline but decreasing plasma atrial natriuretic factor in chronic heart failure. Auton Autacoid Pharmacol. 2002 Oct-Dec;22(5-6):261-8. doi: 10.1046/j.1474-8673.2002.00266.x.
19 The effects of clonidine hydrochloride versus atenolol monotherapy on serum lipids, lipid subfractions, and apolipoproteins in mild hypertension. Am Heart J. 1990 Jul;120(1):172-9. doi: 10.1016/0002-8703(90)90175-w.
20 Atenolol-induced regulation of leukocyte beta 2-adrenoceptors in hypertension. Pharmacology. 1984;29(4):210-4. doi: 10.1159/000138015.
21 A comparison of atenolol and nebivolol in isolated systolic hypertension. J Hypertens. 2008 Feb;26(2):351-6. doi: 10.1097/HJH.0b013e3282f283c9.
22 Folic acid uptake by the human syncytiotrophoblast: interference by pharmacotherapy, drugs of abuse and pathological conditions. Reprod Toxicol. 2009 Dec;28(4):511-20. doi: 10.1016/j.reprotox.2009.07.001. Epub 2009 Jul 16.
23 A 1-year follow-up study on the effect of atenolol on serum beta 2-microglobulin level in hypertensive diabetic patients. J Int Med Res. 1989 Mar-Apr;17(2):162-7. doi: 10.1177/030006058901700208.
24 Beta-blockers restore calcium release channel function and improve cardiac muscle performance in human heart failure. Circulation. 2003 May 20;107(19):2459-66. doi: 10.1161/01.CIR.0000068316.53218.49. Epub 2003 May 12.
25 CACNA1C gene polymorphisms, cardiovascular disease outcomes, and treatment response. Circ Cardiovasc Genet. 2009 Aug;2(4):362-70. doi: 10.1161/CIRCGENETICS.109.857839. Epub 2009 Jun 3.
26 B2 bradykinin receptor (B2BKR) polymorphism and change in left ventricular mass in response to antihypertensive treatment: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial. J Hypertens. 2003 Mar;21(3):621-4. doi: 10.1097/00004872-200303000-00029.
27 Gender-specific association between preproendothelin-1 genotype and reduction of systolic blood pressure during antihypertensive treatment--results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA). Clin Cardiol. 2004 May;27(5):287-90. doi: 10.1002/clc.4960270510.
28 Single nucleotide polymorphisms predict the change in left ventricular mass in response to antihypertensive treatment. J Hypertens. 2004 Dec;22(12):2321-8. doi: 10.1097/00004872-200412000-00014.
29 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.
30 Rate-limiting biotransformation of triamterene is mediated by CYP1A2. Int J Clin Pharmacol Ther. 2005 Jul;43(7):327-34.
31 Identification of chemical compounds that induce HIF-1alpha activity. Toxicol Sci. 2009 Nov;112(1):153-63.
32 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.
33 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.