Repositioning Candidate Details
| Candidate ID: | R0067 |
| Source ID: | DB00257 |
| Source Type: | approved; vet_approved |
| Compound Type: | small molecule |
| Compound Name: | Clotrimazole |
| Synonyms: | |
| Molecular Formula: | C22H17ClN2 |
| SMILES: | ClC1=CC=CC=C1C(N1C=CN=C1)(C1=CC=CC=C1)C1=CC=CC=C1 |
| Structure: |
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| DrugBank Description: | This drug is a broad spectrum antimycotic or antifungal agent. Clotrimazole's antimycotic properties were discovered in the late 1960s [A174094]. Clotrimazole falls under the _imidazole_ category of _azole_ antifungals, possessing broad-spectrum antimycotic activity [A174094]. It is available in various preparations, including creams, pessaries, and troche formulations (slowly dissolving tablets). As well as its antifungal activity, clotrimazole has become a drug of interest in treating several other diseases such as sickle cell disease, malaria and some cancers [A174094]. The minimal side effect profile of this drug and its uncomplicated metabolic profile have led it to gain widespread acceptance for the treatment of mycotic outbreaks such as vaginal yeast infections as well as athlete's foot [A174097]. |
| CAS Number: | 23593-75-1 |
| Molecular Weight: | 344.837 |
| DrugBank Indication: | **Topical preparations** Clotrimazole topical cream is indicated for the topical treatment of the following dermal infections [F3088], [F3121]: Tinea pedis, tinea cruris, and tinea corporis due to _Trichophyton rubrum_, _Trichophyton mentagrophytes_, _Epidermophyton floccosum_ Candidiasis due to _Candida albicans_ Tinea versicolor due to _Malassezia furfur_ Diaper rash infected by _Candida albicans_ In some preparations, clotrimazole may be combined with betamethasone dipropionate, a corticosteroid [F3121]. **Oral preparations** The oral troche preparation is indicated for the local treatment of oropharyngeal candidiasis [FDA label]. It is also indicated as a prophylactic drug to reduce the incidence of oropharyngeal candidiasis in patients immunocompromised by conditions such as chemotherapy, radiotherapy, or steroid therapy utilized in the treatment of leukemia, solid tumors, or renal transplantation [FDA label]. Troche preparations are not indicated for the treatment of any systemic mycoses [FDA label]. |
| DrugBank Pharmacology: | Clotrimazole is a broad-spectrum antifungal agent that inhibits the growth of pathogenic yeasts by changing the permeability of cell membranes. The action of clotrimazole is fungistatic at concentrations of drug up to 20 mcg/mL and may be fungicidal _in vitro_ against Candida albicans and other species of the genus Candida at higher concentrations [FDA label]. Unfortunately, resistance to clotrimazole, which was rare in the past, is now common in various patient populations [A174094]. Clotrimazole is generally considered to be a fungistatic, and not a fungicidal drug, although this contrast is not absolute, as clotrimazole shows fungicidal properties at higher concentrations [A174094]. |
| DrugBank MoA: | Clotrimazole acts primarily by damaging the permeability barrier in the cell membrane of fungi. Clotrimazole causes inhibition of ergosterol biosynthesis, an essential constituent of fungal cell membranes. If ergosterol synthesis is either completely or partially inhibited, the cell is no longer able to construct an intact and functional cell membrane [F3088],[F3100]. Because ergosterol directly promotes the growth of fungal cells in a hormone‐like fashion, rapid onset of the above events leads to dose-dependent inhibition of fungal growth [A174094]. Though decreased ergosterol, due to the inhibition of lanosterol 14-demethylase (also known as _CYP51_) [A174094] is accepted to be primarily responsible for the antimycotic properties of clotrimazole, this drug also shows other pharmacological effects. These include the inhibition of sarcoplasmic reticulum Ca2+‐ATPase, depletion of intracellular calcium, and blocking of calcium‐dependent potassium channels and voltage‐dependent calcium channels [A174094]. The action of clotrimazole on these targets accounts for other effects of this drug that are separate from its antimycotic activities [A174094]. |
| Targets: | Cytochrome P450 51; Intermediate conductance calcium-activated potassium channel protein 4; Ergosterol; Nuclear receptor subfamily 1 group I member 2; Hydroxycarboxylic acid receptor 2 |
| Inclusion Criteria: |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
|---|
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T03 | Angiotensin-converting enzyme | ACE | INHIBITOR | Target is a single protein chain | P12821 | ACE_HUMAN | Details |
| T06 | Sulfonylurea receptor 1 | ABCC8 | Target is a single protein chain | Q09428 | ABCC8_HUMAN | Details | |
| T13 | Renin | REN | INHIBITOR | Target is a single protein chain | P00797 | REN_HUMAN | Details |
| T47 | Sialin | SLC17A5 | Target is a single protein chain | Q9NRA2 | SLC17A5_HUMAN | Details | |
| T15 | Steryl-sulfatase | STS | INHIBITOR | Hydrolase | P08842 | STS_HUMAN | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I02 | 1184 | nephrotic syndrome | "A nephrosis characterized by marked increase in glomerular protein permeability resulting in marked elevation of urine protein levels, hypoalbuminemia, hyperlipidemia, and hypercoagulability." [url:https\://en.wikipedia.org/wiki/Nephrotic_syndrome, url:https\://www.niddk.nih.gov/health-information/kidney-disease/nephrotic-syndrome-adults] | Details |