General Information of Drug Combination (ID: DC7C247)

Drug Combination Name
ZM-447439 Miconazole
Indication
Disease Entry Status REF
DD2 Investigative [1]
Component Drugs ZM-447439   DMFP8WE Miconazole   DMPMYE8
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: DD2
Zero Interaction Potency (ZIP) Score: 6.285
Bliss Independence Score: 5.329
Loewe Additivity Score: 0.621
LHighest Single Agent (HSA) Score: 5.98

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of ZM-447439
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [2]
ZM-447439 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Aurora kinase A (AURKA) TTPS3C0 AURKA_HUMAN Inhibitor [5]
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ZM-447439 Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Neurogenic locus notch homolog protein 1 (NOTCH1) OTI1WADQ NOTC1_HUMAN Increases Expression [6]
Aurora kinase B (AURKB) OTIY4VHU AURKB_HUMAN Affects Localization [7]
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Indication(s) of Miconazole
Disease Entry ICD 11 Status REF
Cutaneous candidiasis 1F23.14 Approved [3]
Fungal infection 1F29-1F2F Approved [4]
Mycoses 1F2Z Approved [3]
Onychomycosis EE12.1 Approved [3]
Tinea corporis 1F28.Y Approved [3]
Tinea cruris 1F28.3 Approved [3]
Tinea versicolor 1F2D.0 Approved [3]
Tinea pedis 1F28.2 Investigative [3]
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 [8]
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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 [9]
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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 [10]
Cytochrome P450 2C9 (CYP2C9) OTGLBN29 CP2C9_HUMAN Decreases Activity [11]
Aromatase (CYP19A1) OTZ6XF74 CP19A_HUMAN Decreases Activity [12]
Nuclear receptor subfamily 1 group I member 2 (NR1I2) OTC5U0N5 NR1I2_HUMAN Decreases Expression [13]
Tyrosine aminotransferase (TAT) OT2CJ91O ATTY_HUMAN Decreases Expression [13]
Nuclear receptor subfamily 1 group I member 3 (NR1I3) OTS3SGH7 NR1I3_HUMAN Decreases Expression [13]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Decreases Activity [14]
Adenylate cyclase type 9 (ADCY9) OT1IZT5K ADCY9_HUMAN Increases Activity [15]
Steroid 17-alpha-hydroxylase/17,20 lyase (CYP17A1) OTZKVLVJ CP17A_HUMAN Decreases Activity [16]
Interleukin-4 (IL4) OTOXBWAU IL4_HUMAN Decreases Expression [17]
Interleukin-5 (IL5) OTAFPSCO IL5_HUMAN Decreases Expression [17]
Cathepsin D (CTSD) OTQZ36F3 CATD_HUMAN Increases Expression [18]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [18]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [19]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Increases Expression [18]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B) OTUYHB84 MLP3B_HUMAN Increases Lipidation [18]
Lanosterol 14-alpha demethylase (CYP51A1) OTAYHG9C CP51A_HUMAN Decreases Response To Substance [20]
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⏷ Show the Full List of 17 DOT(s)

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: 8353).
3 Miconazole FDA Label
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: 2449).
5 Accurate prediction of the relative potencies of members of a series of kinase inhibitors using molecular docking and MM-GBSA scoring. J Med Chem. 2006 Aug 10;49(16):4805-8.
6 PLK1 targets NOTCH1 during DNA damage and mitotic progression. J Biol Chem. 2019 Nov 22;294(47):17941-17950. doi: 10.1074/jbc.RA119.009881. Epub 2019 Oct 9.
7 DNA double-strand breaks and Aurora B mislocalization induced by exposure of early mitotic cells to H(2)O(2) appear to increase chromatin bridges and resultant cytokinesis failure. Free Radic Biol Med. 2017 Jul;108:129-145. doi: 10.1016/j.freeradbiomed.2017.03.025. Epub 2017 Mar 24.
8 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
9 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.
10 Azole antimycotics differentially affect rifampicin-induced pregnane X receptor-mediated CYP3A4 gene expression. Drug Metab Dispos. 2008 Feb;36(2):339-48.
11 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.
12 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.
13 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.
14 In vitro inhibitory effects of asiaticoside and madecassoside on human cytochrome P450. Toxicol In Vitro. 2011 Jun;25(4):890-6.
15 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.
16 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.
17 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.
18 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.
19 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.
20 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.