Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM3KN7V)

• Drug Name: Bifonazole Drug Info
• Synonyms: Amycor; Azolmen; Bifokey; Bifomyk; Bifon; Bifonazol; Bifonazolum; Moldina; Mycospor; Trifonazole; Bayer brand of bifonazole; Bioglan brand of bifonazole; Canesten Extra Bifonazol; Canesten brand of bifonazole; Dermapharm brand of bifonazole; Inkeysa brand of bifonazole; Juventus brand of bifonazole; Merck Lipha Sante brand of bifonazole; Bay H-4502; Bifonazol [INN-Spanish]; Bifonazolum [INN-Latin]; Canespor (TN); Mycospor (TN); Bay-h-4502; Bifonazole (JP15/USAN/INN); Bifonazole [USAN:BAN:INN:JAN]; (+-)-1-([1,1'-Biphenyl]-4-ylphenylmethyl)-1H-imidazole; (+-)-1-(p,alpha-Diphenylbenzyl)imidazole; 1-((4-Biphenylyl)phenylmethyl)-1H-imidazole; 1-(alpha-(4-Biphenylyl)benzyl)imidazole; 1-(p,alpha-Diphenylbenzyl)imidazole; 1-[4,alpha-Diphenylbenzyl]-imidazole; 1-[biphenyl-4-yl(phenyl)methyl]-1H-imidazole; 1-[phenyl-(4-phenylphenyl)methyl]imidazole

Indication

Disease Entry	ICD 11	Status	REF
Fungal infection	1F29-1F2F	Approved	[1]

• Therapeutic Class: Antifungal Agents
• Cross-matching ID:
  PubChem CID: 2378
  ChEBI ID: CHEBI:78692
  CAS Number: CAS 60628-96-8
  TTD Drug ID: DM3KN7V

Molecule-Related Drug Atlas

Drug(s) Targeting Candida Cytochrome P450 51 (Candi ERG11)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Voriconazole	DMAOL2S	Aspergillosis	1F20	Approved	[6]
Itraconazole	DMCR1MV	Aspergillosis	1F20	Approved	[6]
Posaconazole	DMUL5EW	Aspergillosis	1F20	Approved	[7]
Ketoconazole	DMPZI3Q	Blastomycosis	1F22	Approved	[8]
Miconazole	DMPMYE8	Cutaneous candidiasis	1F23.14	Approved	[6]
Oxiconazole	DME7KRM	Tinea corporis	1F28.Y	Approved	[9]
Fluconazole	DMOWZ6B	Cryptococcal meningitis		Approved	[6]
Terconazole	DMJ13KI	Candidiasis	1F23	Approved	[10]
Tioconazole	DMNYPGS	Onychomycosis	EE12.1	Approved	[11]
Econazole	DMFSWGH	Cutaneous candidiasis	1F23.14	Approved	[12]

Drug(s) Affected By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Eplerenone	DMF0NQR	Heart failure	BD10-BD13	Approved	[13]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[14]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[15]
Voriconazole	DMAOL2S	Aspergillosis	1F20	Approved	[16]
Proguanil	DMBL79I	Malaria	1F40-1F45	Approved	[17]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[17]
Loratadine	DMF3AN7	Allergy	4A80-4A85	Approved	[18]
Nelfinavir mesylate	DMFX6G8	N. A.	N. A.	Approved	[19]
Capsaicin	DMGMF6V	Back pain	ME84.Z	Approved	[20]
Axitinib	DMGVH6N	Renal cell carcinoma	2C90	Approved	[21]

Drug(s) Affected By Aromatase (CYP19A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Letrozole	DMH07Y3	Estrogen-receptor positive breast cancer		Approved	[22]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[23]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[24]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[25]
Citalopram	DM2G9AE	Acute coronary syndrome	BA41	Approved	[24]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[26]
FADROZOLE	DM3C5GZ	Breast cancer	2C60-2C65	Approved	[27]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[28]
Fluoxetine	DM3PD2C	Bipolar depression		Approved	[24]
obeticholic acid	DM3Q1SM	Primary biliary cholangitis	DB96.1	Approved	[29]

Drug(s) Affected By Lanosterol 14-alpha demethylase (CYP51A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[30]
FADROZOLE	DM3C5GZ	Breast cancer	2C60-2C65	Approved	[5]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[31]
obeticholic acid	DM3Q1SM	Primary biliary cholangitis	DB96.1	Approved	[29]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[32]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[33]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[34]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[35]
Leflunomide	DMR8ONJ	Arthritis	FA20	Approved	[36]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[37]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Candida Cytochrome P450 51 (Candi ERG11)	TTTSOUD	CP51_CANAL	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Gene/Protein Processing	[3]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Gene/Protein Processing	[4]
Lanosterol 14-alpha demethylase (CYP51A1)	OTAYHG9C	CP51A_HUMAN	Gene/Protein Processing	[5]

References

• [1] Drug information of Bifonazole, 2008. eduDrugs.
• [2] Investigation of the role of cytochrome P450 2B4 active site residues in substrate metabolism based on crystal structures of the ligand-bound enzyme. Arch Biochem Biophys. 2006 Nov 1;455(1):61-7.
• [3] 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.
• [4] 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.
• [5] Comparison of lanosterol-14 alpha-demethylase (CYP51) of human and Candida albicans for inhibition by different antifungal azoles. Toxicology. 2006 Nov 10;228(1):24-32. doi: 10.1016/j.tox.2006.08.007. Epub 2006 Aug 12.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [7] A new, broad-spectrum azole antifungal: posaconazole--mechanisms of action and resistance, spectrum of activity. Mycoses. 2006;49 Suppl 1:2-6.
• [8] Clinical pharmacokinetics and pharmacodynamics of solifenacin. Clin Pharmacokinet. 2009;48(5):281-302.
• [9] Antifungal agents: mechanisms of action. Trends Microbiol. 2003 Jun;11(6):272-9.
• [10] Mode of action of anti-Candida drugs: focus on terconazole and other ergosterol biosynthesis inhibitors. Am J Obstet Gynecol. 1991 Oct;165(4 Pt 2):1193-9.
• [11] Biological spectra analysis: Linking biological activity profiles to molecular structure. Proc Natl Acad Sci U S A. 2005 Jan 11;102(2):261-6.
• [12] 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.
• [13] The relative role of CYP3A4 and CYP3A5 in eplerenone metabolism. Toxicol Lett. 2019 Oct 15;315:9-13.
• [14] Characterization of the structural determinants required for potent mechanism-based inhibition of human cytochrome P450 1A1 by cannabidiol. Chem Biol Interact. 2014 May 25;215:62-8.
• [15] Retinoids activate the RXR/SXR-mediated pathway and induce the endogenous CYP3A4 activity in Huh7 human hepatoma cells. Toxicol Sci. 2006 Jul;92(1):51-60.
• [16] 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.
• [17] Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s. Drug Metab Dispos. 2001 Jan;29(1):30-5.
• [18] Cetirizine and loratadine-based antihistamines with 5-lipoxygenase inhibitory activity. Bioorg Med Chem Lett. 2004 Nov 15;14(22):5591-4.
• [19] Mechanism-based inactivation of CYP3A by HIV protease inhibitors. J Pharmacol Exp Ther. 2005 Feb;312(2):583-91.
• [20] Studies of the toxicological potential of capsinoids, XIII: inhibitory effects of capsaicin and capsinoids on cytochrome P450 3A4 in human liver microsomes. Int J Toxicol. 2010 Mar;29(2 Suppl):22S-6S.
• [21] Investigation of the effects of axitinib on the pharmacokinetics of loperamide and its main metabolite N-demethylated loperamide in rats by UPLC-MS/MS. Chem Biol Interact. 2019 Sep 1;310:108744. doi: 10.1016/j.cbi.2019.108744. Epub 2019 Jul 9.
• [22] Aromatase inhibition: translation into a successful therapeutic approach. Clin Cancer Res. 2005 Apr 15;11(8):2809-21. doi: 10.1158/1078-0432.CCR-04-2187.
• [23] Cannabidiol (CBD) but not tetrahydrocannabinol (THC) dysregulate in vitro decidualization of human endometrial stromal cells by disruption of estrogen signaling. Reprod Toxicol. 2020 Apr;93:75-82. doi: 10.1016/j.reprotox.2020.01.003. Epub 2020 Jan 14.
• [24] Effects of selective serotonin reuptake inhibitors on three sex steroids in two versions of the aromatase enzyme inhibition assay and in the H295R cell assay. Toxicol In Vitro. 2015 Oct;29(7):1729-35.
• [25] Arsenite and cadmium promote the development of mammary tumors. Carcinogenesis. 2020 Jul 14;41(7):1005-1014. doi: 10.1093/carcin/bgz176.
• [26] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [27] Synthesis and evaluation of (pyridylmethylene)tetrahydronaphthalenes/-indanes and structurally modified derivatives: potent and selective inhibitors of aldosterone synthase. J Med Chem. 2005 Mar 10;48(5):1563-75.
• [28] Estrogen synthesis in human colon cancer epithelial cells. J Steroid Biochem Mol Biol. 1999 Dec 31;71(5-6):223-30.
• [29] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [30] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [31] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [32] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [33] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [34] JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
• [35] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [36] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [37] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.