General Information of Drug Combination (ID: DCNQ5DC)

Drug Combination Name
1-((2-chlorophenyl)diphenylmethyl)-1H-pyrazole Itraconazole
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs 1-((2-chlorophenyl)diphenylmethyl)-1H-pyrazole   DMQEJVU 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: 7.98
Bliss Independence Score: 7.98
Loewe Additivity Score: 22.13
LHighest Single Agent (HSA) Score: 22.13

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of 1-((2-chlorophenyl)diphenylmethyl)-1H-pyrazole
Disease Entry ICD 11 Status REF
Conjunctival fibrosis 9A61.3 Investigative [2]
1-((2-chlorophenyl)diphenylmethyl)-1H-pyrazole Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Calcium-activated potassium channel (KCN) TTMNI76 NOUNIPROTAC Inhibitor [5]
Calcium-activated potassium channel KCa3.1 (KCNN4) TT7M9I6 KCNN4_HUMAN Blocker (channel blocker) [6]
------------------------------------------------------------------------------------
1-((2-chlorophenyl)diphenylmethyl)-1H-pyrazole Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Estrogen receptor (ESR1) OTKLU61J ESR1_HUMAN Decreases Expression [7]
Progesterone receptor (PGR) OT0FZ3QE PRGR_HUMAN Increases Expression [7]
------------------------------------------------------------------------------------
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 [8]
Candida Cytochrome P450 51 (Candi ERG11) TTTSOUD CP51_CANAL Modulator [9]
------------------------------------------------------------------------------------
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 [10]
------------------------------------------------------------------------------------
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 [11]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [12]
------------------------------------------------------------------------------------
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 [13]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Decreases Activity [14]
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial (CYP24A1) OTG2T749 CP24A_HUMAN Decreases Activity [15]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Increases Expression [16]
Nuclear receptor subfamily 1 group I member 2 (NR1I2) OTC5U0N5 NR1I2_HUMAN Increases Expression [17]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [18]
Interleukin-4 (IL4) OTOXBWAU IL4_HUMAN Decreases Expression [19]
Interleukin-5 (IL5) OTAFPSCO IL5_HUMAN Decreases Expression [19]
11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2) OTHF4H9U DHI2_HUMAN Decreases Activity [20]
Lanosterol 14-alpha demethylase (CYP51A1) OTAYHG9C CP51A_HUMAN Decreases Response To Substance [21]
------------------------------------------------------------------------------------
⏷ 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 Blockade of KCa3.1: A novel target to treat TGF-1 induced conjunctival fibrosis.Exp Eye Res. 2018 Feb;167:140-144.
3 Itraconazole FDA Label
4 FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 076104.
5 Inhibitors of potassium channels KV1.3 and IK-1 as immunosuppressants. Bioorg Med Chem Lett. 2009 Apr 15;19(8):2299-304.
6 Blockade of the intermediate-conductance calcium-activated potassium channel as a new therapeutic strategy for restenosis. Circulation. 2003 Sep 2;108(9):1119-25.
7 The intermediate conductance Ca2+-activated K+ channel inhibitor TRAM-34 stimulates proliferation of breast cancer cells via activation of oestrogen receptors. Br J Pharmacol. 2010 Feb 1;159(3):650-8. doi: 10.1111/j.1476-5381.2009.00557.x. Epub 2009 Dec 24.
8 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
9 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
10 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.
11 Effects of itraconazole and tandospirone on the pharmacokinetics of perospirone. Ther Drug Monit. 2006 Feb;28(1):73-5.
12 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.
13 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.
14 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.
15 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.
16 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.
17 Azole antimycotics differentially affect rifampicin-induced pregnane X receptor-mediated CYP3A4 gene expression. Drug Metab Dispos. 2008 Feb;36(2):339-48.
18 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.
19 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.
20 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.
21 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.