| Candidate ID: | R0407 |
| Source ID: | DB01110 |
| Source Type: | approved; investigational; vet_approved |
| Compound Type: |
small molecule
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| Compound Name: |
Miconazole
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| Synonyms: |
1-(2,4-Dichloro-beta-((2,4-dichlorobenzyl)oxy)phenethyl)imidazole; 1-[2-(2,4-Dichloro-benzyloxy)-2-(2,4-dichloro-phenyl)-ethyl]-1H-imidazole; Miconazole
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| Molecular Formula: |
C18H14Cl4N2O
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| SMILES: |
ClC1=CC(Cl)=C(COC(CN2C=CN=C2)C2=C(Cl)C=C(Cl)C=C2)C=C1
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| Structure: |
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| DrugBank Description: |
Miconazole is a broad-spectrum azole antifungal with some activity against Gram-positive bacteria as well. It is widely used to treat mucosal yeast infections, including both oral and vaginal infections; although intravenous miconazole is no longer available, a wide variety of suppositories, creams, gels, and tablet-based products are available. Miconazole is thought to act primarily through the inhibition of fungal CYP450 14α-lanosterol demethylase activity.
Miconazole was first synthesized in 1969 and first granted FDA approval on January 8, 1974, for sale by INSIGHT Pharmaceuticals as a topical cream. It is currently available as a variety of prescription and over the counter products. Despite having been in clinical use for an extended period, resistance to miconazole among susceptible organisms is relatively low.
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| CAS Number: |
22916-47-8
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| Molecular Weight: |
416.129
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| DrugBank Indication: |
Miconazole is indicated for the local treatment of oropharyngeal candidiasis in adult patients and for the adjunctive treatment of diaper dermatitis complicated by candidiasis in immunocompetent patients aged four weeks and older. Miconazole is available as both a suppository and cream for the treatment of vaginal yeast infections and the relief of associated vulvar itching and irritation. Lastly, miconazole cream is effective in treating athlete's foot (tinea pedis), jock itch (tinea cruris), ringworm infections (tinea corporis), pityriasis (formerly tinea) versicolor, and cutaneous candidiasis.
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| DrugBank Pharmacology: |
Miconazole is an azole antifungal that functions primarily through inhibition of a specific demethylase within the CYP450 complex. As miconazole is typically applied topically and is minimally absorbed into the systemic circulation following application, the majority of patient reactions are limited to hypersensitivity and cases of anaphylaxis. Patients using intravaginal miconazole products are advised not to rely on contraceptives to prevent pregnancy and sexually transmitted infections, as well as not to use tampons concurrently.
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| DrugBank MoA: |
Miconazole is an azole antifungal used to treat a variety of conditions, including those caused by _Candida_ overgrowth. Unique among the azoles, miconazole is thought to act through three main mechanisms. The primary mechanism of action is through inhibition of the CYP450 14α-lanosterol demethylase enzyme, which results in altered ergosterol production and impaired cell membrane composition and permeability, which in turn leads to cation, phosphate, and low molecular weight protein leakage.
In addition, miconazole inhibits fungal peroxidase and catalase while not affecting NADH oxidase activity, leading to increased production of reactive oxygen species (ROS). Increased intracellular ROS leads to downstream pleiotropic effects and eventual apoptosis.
Lastly, likely as a result of lanosterol demethylation inhibition, miconazole causes a rise in intracellular levels of farnesol. This molecule participates in quorum sensing in _Candida_, preventing the transition from yeast to mycelial forms and thereby the formation of biofilms, which are more resistant to antibiotics. In addition, farnesol is an inhibitor of drug efflux ABC transporters, namely _Candida_ CaCdr1p and CaCdr2p, which may additionally contribute to increased effectiveness of azole drugs.
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| Targets: |
Cytochrome P450 51 inhibitor; Nitric oxide synthase, endothelial inhibitor; Nitric oxide synthase, inducible inhibitor; Nuclear receptor subfamily 1 group I member 2 partial agonist; Calcium-activated potassium channel inhibitor; Voltage-gated Potassium Channels inhibitor; Inward rectifier potassium channel inhibitor; Voltage gated L-type calcium channel inhibitor
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| Inclusion Criteria: |
Therapeutic strategy associated
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