General Information of Drug Combination (ID: DCK1BYF)

Drug Combination Name
Miconazole Olmesartan medoxomil
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Miconazole   DMPMYE8 Olmesartan medoxomil   DMWBHRY
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: 16.83
Bliss Independence Score: 16.83
Loewe Additivity Score: 25.62
LHighest Single Agent (HSA) Score: 25.62

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Miconazole
Disease Entry ICD 11 Status REF
Cutaneous candidiasis 1F23.14 Approved [2]
Fungal infection 1F29-1F2F Approved [3]
Mycoses 1F2Z Approved [2]
Onychomycosis EE12.1 Approved [2]
Tinea corporis 1F28.Y Approved [2]
Tinea cruris 1F28.3 Approved [2]
Tinea versicolor 1F2D.0 Approved [2]
Tinea pedis 1F28.2 Investigative [2]
Miconazole Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Candida Cytochrome P450 51 (Candi ERG11) TTTSOUD CP51_CANAL Modulator [5]
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Miconazole Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [6]
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Miconazole Interacts with 17 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [7]
Cytochrome P450 2C9 (CYP2C9) OTGLBN29 CP2C9_HUMAN Decreases Activity [8]
Aromatase (CYP19A1) OTZ6XF74 CP19A_HUMAN Decreases Activity [9]
Nuclear receptor subfamily 1 group I member 2 (NR1I2) OTC5U0N5 NR1I2_HUMAN Decreases Expression [10]
Tyrosine aminotransferase (TAT) OT2CJ91O ATTY_HUMAN Decreases Expression [10]
Nuclear receptor subfamily 1 group I member 3 (NR1I3) OTS3SGH7 NR1I3_HUMAN Decreases Expression [10]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Decreases Activity [11]
Adenylate cyclase type 9 (ADCY9) OT1IZT5K ADCY9_HUMAN Increases Activity [12]
Steroid 17-alpha-hydroxylase/17,20 lyase (CYP17A1) OTZKVLVJ CP17A_HUMAN Decreases Activity [13]
Interleukin-4 (IL4) OTOXBWAU IL4_HUMAN Decreases Expression [14]
Interleukin-5 (IL5) OTAFPSCO IL5_HUMAN Decreases Expression [14]
Cathepsin D (CTSD) OTQZ36F3 CATD_HUMAN Increases Expression [15]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [15]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [16]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Increases Expression [15]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B) OTUYHB84 MLP3B_HUMAN Increases Lipidation [15]
Lanosterol 14-alpha demethylase (CYP51A1) OTAYHG9C CP51A_HUMAN Decreases Response To Substance [17]
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⏷ Show the Full List of 17 DOT(s)
Indication(s) of Olmesartan medoxomil
Disease Entry ICD 11 Status REF
High blood pressure BA00 Approved [4]
Olmesartan medoxomil Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Angiotensin II receptor type-1 (AGTR1) TT8DBY3 AGTR1_HUMAN Antagonist [18]
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Olmesartan medoxomil Interacts with 8 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [19]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [20]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [21]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [22]
Multidrug resistance-associated protein 4 (ABCC4) DTCSGPB MRP4_HUMAN Substrate [19]
Organic anion transporter 1 (SLC22A6) DTQ23VB S22A6_HUMAN Substrate [19]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [19]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [19]
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⏷ Show the Full List of 8 DTP(s)
Olmesartan medoxomil Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [23]
Tight junction protein ZO-1 (TJP1) OTBDCUPK ZO1_HUMAN Affects Localization [24]
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References

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2 Miconazole 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: 2449).
4 Effect of angiotensin receptor blockade on endothelial function: focus on olmesartan medoxomil. Vasc Health Risk Manag. 2009;5(1):301-14.
5 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
6 Inhibition of cytochrome P450 enzymes participating in p-nitrophenol hydroxylation by drugs known as CYP2E1 inhibitors. Chem Biol Interact. 2004 Apr 15;147(3):331-40.
7 Azole antimycotics differentially affect rifampicin-induced pregnane X receptor-mediated CYP3A4 gene expression. Drug Metab Dispos. 2008 Feb;36(2):339-48.
8 The novel azole R126638 is a selective inhibitor of ergosterol synthesis in Candida albicans, Trichophyton spp., and Microsporum canis. Antimicrob Agents Chemother. 2004 Sep;48(9):3272-8.
9 Comparative assessment of the inhibition of recombinant human CYP19 (aromatase) by azoles used in agriculture and as drugs for humans. Endocr Res. 2004 Aug;30(3):387-94.
10 Ketoconazole and miconazole are antagonists of the human glucocorticoid receptor: consequences on the expression and function of the constitutive androstane receptor and the pregnane X receptor. Mol Pharmacol. 2006 Jul;70(1):329-39.
11 In vitro inhibitory effects of asiaticoside and madecassoside on human cytochrome P450. Toxicol In Vitro. 2011 Jun;25(4):890-6.
12 Direct stimulation of adenylyl cyclase 9 by the fungicide imidazole miconazole. Naunyn Schmiedebergs Arch Pharmacol. 2019 Apr;392(4):497-504. doi: 10.1007/s00210-018-01610-1. Epub 2019 Jan 3.
13 The classic azole antifungal drugs are highly potent endocrine disruptors in vitro inhibiting steroidogenic CYP enzymes at concentrations lower than therapeutic Cmax. Toxicology. 2019 Sep 1;425:152247. doi: 10.1016/j.tox.2019.152247. Epub 2019 Jul 19.
14 Anti-mycotics suppress interleukin-4 and interleukin-5 production in anti-CD3 plus anti-CD28-stimulated T cells from patients with atopic dermatitis. J Invest Dermatol. 2001 Dec;117(6):1635-46. doi: 10.1046/j.0022-202x.2001.01566.x.
15 Miconazole induces protective autophagy in bladder cancer cells. Environ Toxicol. 2021 Feb;36(2):185-193. doi: 10.1002/tox.23024. Epub 2020 Sep 27.
16 Why are most phospholipidosis inducers also hERG blockers?. Arch Toxicol. 2017 Dec;91(12):3885-3895. doi: 10.1007/s00204-017-1995-9. Epub 2017 May 27.
17 Differential azole antifungal efficacies contrasted using a Saccharomyces cerevisiae strain humanized for sterol 14 alpha-demethylase at the homolo... Antimicrob Agents Chemother. 2008 Oct;52(10):3597-603.
18 Mechanism of diastolic stiffening of the failing myocardium and its prevention by angiotensin receptor and calcium channel blockers. J Cardiovasc Pharmacol. 2009 Jul;54(1):47-56.
19 Multiple human isoforms of drug transporters contribute to the hepatic and renal transport of olmesartan, a selective antagonist of the angiotensin II AT1-receptor. Drug Metab Dispos. 2007 Dec;35(12):2166-76.
20 KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01665)
21 KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01913)
22 OATP1B1, OATP1B3, and mrp2 are involved in hepatobiliary transport of olmesartan, a novel angiotensin II blocker. Drug Metab Dispos. 2006 May;34(5):862-9.
23 A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci. 2013 Nov;136(1):216-41.
24 Immunopathogenesis of olmesartan-associated enteropathy. Aliment Pharmacol Ther. 2015 Dec;42(11-12):1303-14. doi: 10.1111/apt.13413. Epub 2015 Oct 1.