General Information of Drug Combination (ID: DCLEMOM)

Drug Combination Name
Desoxycorticosterone Pivalate Itraconazole
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Desoxycorticosterone Pivalate   DMSA4B3 Itraconazole   DMCR1MV
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: 56.42
Bliss Independence Score: 56.42
Loewe Additivity Score: 70.04
LHighest Single Agent (HSA) Score: 70.04

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Desoxycorticosterone Pivalate
Disease Entry ICD 11 Status REF
Addison disease 5A74.0 Approved [2]
Desoxycorticosterone Pivalate Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Mineralocorticoid receptor (MR) TT26PHO MCR_HUMAN Binder [5]
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Desoxycorticosterone Pivalate 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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Indication(s) of Itraconazole
Disease Entry ICD 11 Status REF
Aspergillosis 1F20 Approved [3]
Blastomycosis 1F22 Approved [3]
Fungal infection 1F29-1F2F Approved [4]
Fusariosis N.A. Approved [3]
Histoplasmosis N.A. Approved [3]
Invasive candidiasis 1F23 Approved [3]
Mycoses 1F2Z Approved [3]
Candidemia 1F23.3Y Investigative [3]
Esophageal candidiasis N.A. Investigative [3]
Itraconazole Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Hedgehog signaling pathway (HS pathway) TT4LXBC NOUNIPROTAC Inhibitor [7]
Candida Cytochrome P450 51 (Candi ERG11) TTTSOUD CP51_CANAL Modulator [8]
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Itraconazole Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [9]
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Itraconazole Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [10]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [11]
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Itraconazole Interacts with 10 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Decreases Expression [12]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Decreases Activity [13]
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial (CYP24A1) OTG2T749 CP24A_HUMAN Decreases Activity [14]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Increases Expression [15]
Nuclear receptor subfamily 1 group I member 2 (NR1I2) OTC5U0N5 NR1I2_HUMAN Increases Expression [16]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [17]
Interleukin-4 (IL4) OTOXBWAU IL4_HUMAN Decreases Expression [18]
Interleukin-5 (IL5) OTAFPSCO IL5_HUMAN Decreases Expression [18]
11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2) OTHF4H9U DHI2_HUMAN Decreases Activity [19]
Lanosterol 14-alpha demethylase (CYP51A1) OTAYHG9C CP51A_HUMAN Decreases Response To Substance [20]
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⏷ Show the Full List of 10 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 Drug information of Desoxycorticosterone Pivalate, 2008. eduDrugs.
3 Itraconazole FDA Label
4 FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 076104.
5 Characterization of rat brain aldosterone receptors reveals high affinity for corticosterone. Endocrinology. 1983 Dec;113(6):2043-51.
6 Progress in Brain Research. Chapter 11 - Steroidogenic Enzymes in the Brain: Morphological Aspects. 2010, 181:193-207.
7 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
8 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
9 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
10 Effects of itraconazole and tandospirone on the pharmacokinetics of perospirone. Ther Drug Monit. 2006 Feb;28(1):73-5.
11 Investigation into UDP-glucuronosyltransferase (UGT) enzyme kinetics of imidazole- and triazole-containing antifungal drugs in human liver microsomes and recombinant UGT enzymes. Drug Metab Dispos. 2010 Jun;38(6):923-9.
12 Itraconazole cis-diastereoisomers activate aryl hydrocarbon receptor AhR and pregnane X receptor PXR and induce CYP1A1 in human cell lines and human hepatocytes. Toxicology. 2017 May 15;383:40-49.
13 Clinical pharmacokinetic monitoring of itraconazole is warranted in only a subset of patients. Ther Drug Monit. 2005 Jun;27(3):322-33. doi: 10.1097/01.ftd.0000150135.22645.ea.
14 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.
15 Induction of cytochrome P450 1A1 by ketoconazole and itraconazole but not fluconazole in murine and human hepatoma cell lines. Toxicol Sci. 2007 May;97(1):32-43.
16 Azole antimycotics differentially affect rifampicin-induced pregnane X receptor-mediated CYP3A4 gene expression. Drug Metab Dispos. 2008 Feb;36(2):339-48.
17 Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci. 2010 Dec; 118(2):485-500.
18 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.
19 Inhibition of 11-hydroxysteroid dehydrogenase 2 by the fungicides itraconazole and posaconazole. Biochem Pharmacol. 2017 Apr 15;130:93-103. doi: 10.1016/j.bcp.2017.01.010. Epub 2017 Jan 25.
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.