Repositioning Candidate Details
| Candidate ID: | R0049 |
| Source ID: | DB00196 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Fluconazole |
| Synonyms: | |
| Molecular Formula: | C13H12F2N6O |
| SMILES: | OC(CN1C=NC=N1)(CN1C=NC=N1)C1=C(F)C=C(F)C=C1 |
| Structure: |
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| DrugBank Description: | Fluconazole, commonly known as _Diflucan_, is an antifungal drug used for the treatment of both systemic and superficial fungal infections in a variety of tissues. It was initially approved by the FDA in 1990. This drug is an _azole_ antifungal, in the same drug family as [ketoconazole] and [itraconazole]. Fluconazole has many advantages over the other antifungal drugs including the option of oral administration. The side effect profile of this drug is minimal. It has been demonstrated as an efficacious treatment for vaginal yeast infections in one single dose.[A174325] |
| CAS Number: | 86386-73-4 |
| Molecular Weight: | 306.2708 |
| DrugBank Indication: | Fluconazole can be administered in the treatment of the following fungal infections[FDA label]: 1) Vaginal yeast infections caused by Candida 2) Systemic Candida infections 3) Both esophageal and oropharyngeal candidiasis 4) Cryptococcal meningitis 5) UTI (urinary tract infection) by Candida 6) Peritonitis (inflammation of the peritoneum) caused by Candida **A note on fungal infection prophylaxis** Patients receiving bone marrow transplantation who are treated with cytotoxic chemotherapy and/or radiation therapy may be predisposed to candida infections, and may receive fluconazole as prophylactic therapy.[FDA label] **A note on laboratory testing** Obtaining specimens for fungal culture and other important laboratory studies such as serology or pathology is advised before starting fluconazole therapy in order to isolate the organisms to be eliminated through treatment. It is permissible to start therapy before the results are available, however, adjusting the therapy once laboratory results confirm the causative organism may be necessary.[FDA label] |
| DrugBank Pharmacology: | Fluconazole has been demonstrated to show fungistatic activity against the majority of strains of the following microorganisms, curing fungal infections[FDA label]: _Candida albicans, Candida glabrata (Many strains are intermediately susceptible), Candida parapsilosis, Candida tropicalis, Cryptococcus neoformans_ This is achieved through steroidal inhibition in fungal cells, interfering with cell wall synthesis and growth as well as cell adhesion, thereby treating fungal infections and their symptoms.[FDA label,A174325,A174343] The fungistatic activity of fluconazole has also been shown in normal and immunocompromised animal models with both systemic and intracranial fungal infections caused by _Cryptococcus neoformans_ and for systemic infections caused by Candida albicans.[FDA label] It is important to note that resistant organisms have been found against various strains of organisms treated with fluconazole.[A178759,A178762,A178765] This further substantiates the need to perform susceptibility testing when fluconazole is considered as an antifungal therapy.[A178768,A178786] **A note on steroidal effects of fluconazole** There has been some concern that fluconazole may interfere with and inactivate human steroids/hormones due to the inhibition of hepatic cytochrome enzymes.[L6496] Fluconazole has demonstrated to be more selective for _fungal_ cytochrome P-450 enzymes than for a variety of mammalian cytochrome P-450 enzymes. Fluconazole 50 mg administered daily for up to 28 days in individuals of reproductive age has been show to have no effect on testosterone plasma concentrations of males and plasma concentrations of steroids in females. A 200-400 mg dose of fluconazole showed no clinically relevant effect on steroid levels or on ACTH-stimulated steroid response in healthy males, in one clinical study mentioned on the European Medicines Agency label.[L6496] Other studies have shown no significant effects of fluconazole on steroid levels, further confirming these data.[A174358,A178780] |
| DrugBank MoA: | Fluconazole is a very selective inhibitor of fungal cytochrome P450 dependent enzyme _lanosterol 14-α-demethylase_. This enzyme normally works to convert _lanosterol_ to _ergosterol_, which is necessary for fungal cell wall synthesis. The free nitrogen atom located on the azole ring of fluconazole binds with a single iron atom located in the heme group of lanosterol 14-α-demethylase.[A178774] This prevents oxygen activation and, as a result, inhibits the demethylation of lanosterol, halting the process of ergosterol biosynthesis.[A178777] Methylated sterols are then found to accumulate in the fungal cellular membrane, leading to an arrest of fungal growth.[A178774] These accumulated sterols negatively affect the structure and function of the fungal cell plasma membrane.[A16632] Fluconazole resistance may arise from an alteration in the amount or function of the target enzyme (lanosterol 14-α-demethylase), altered access to this enzyme, or a combination of the above.[A16632] Other mechanisms may also be implicated, and studies are ongoing.[A178783] |
| Targets: | Cytochrome P450 51 |
| Inclusion Criteria: |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S07 | antihypertensive | Anti-fibrosis; Anti-hypertensive; Anti-hypertensive; antihypertensive medications; multidrug combination antihypertensive treatment; empirical addition (or increase in the dose) of an antihypertensive agent of a different class""; Anti-hypertensive; Lifestyle measures; Anti-inflammatory; Improve insulin resistance; Enhance lipid metabolism; Regulating intestinal flora; Anti-hypertensive; Anti-hypertensive; Anti-inflammatory; Anti-fibrosis; Anti-inflammatory; Immunotherapy; Anti-hypertensive; Immunosuppressive treatment; Anti-hypertensive; Anti-hypertensive; Anti-platelet aggregation; other antihypertensive drugs; antihypertensive therapy; Anti-hypertensive; Anti-inflammatory; Anti-hypertensive (standard antihypertensive treatment; intensive antihypertensive treatment); Blood pressure management; Anti-hypertensive; Enhance lipid metabolism; Anti-hypertensive; Enhance lipid metabolism; Anti-platelet aggregation; Improve insulin resistance; Anti-hypertensive; Anti-hypertensive; Anti-oxidative stress; antihypertensives; Lifestyle measures; Anti-hypertensive; Anti-fibrosis; Anti-inflammatory; Anti-hypertensive | ACE; Smad4; PKD1; angiotensin receptor; SGLT2; angiotensin II receptor; mineralocorticoid receptor; ACE | riociguat; sGC stimulators; sGC activators; antihypertensive medications; carvedilol; lercanidipine; enalapril; folic acid; retinoic acid; angiotensin II; antihypertensive drug; Tripterygium Wilfordii Hook F; valsartan; Renin-angiotensin system inhibitors; diuretics; calcium channel blocker; corticosteroid; anti-hypertensive treatment; NSAIDs; naproxen; celecoxib; proton pump inhibitor; non-selective NSAID; selective cyclo-oxygenase-2 inhibitor; renin-angiotensin system blockers; antihypertensive agent; cilnidipine; valsartan; RAAS-is; steroids; immunosuppressors; amiloride; hydrochlorothiazide; berberine; Aliskiren; calcium channel blocker; angiotensin II receptor blocker; ARB; Chlorthalidone; Hydrochlorothiazide; Hsub2/subS; NO; Hsub2/subSxa0; xa0; NO; prednisolone; mizoribine; angiotensin-converting enzyme inhibitors; ACEI; eculizumab; antihypertensive agents; antithrombotics; antianemics; proton pump inhibitors; allopurinol; rilmenidine; long-term benzodiazepines; anticholinergic drugs; hydroxyzine; Qian Yang Yu Yin Granule; RAAS blockers; other antihypertensive drugs; antihypertensives; antihypertensive classes; antihypertensive therapy; melatonin; RAASi; Aliskiren; ARBs; ACEIs; tegafur/gimeracil/oteracil; furosemide; prednisolone; angiotensin receptor blockers; valsartan; antihypertensive drugs; fosinopril; valsartan; Canagliflozin; sodium glucose co-transporter 2 inhibitors; Aspirin; Antihypertensive; Lipid-Lowering Treatment; Sodium-glucose cotransporter 2 inhibitors; angiotensin II receptor blocker; Spironolactone; KBP-5074; captopril; enalaprilate; lisinopril; losartan; valsartan; furosemide; pravastatin; simvastatin; Renin Angiotensin System inhibitors; ACE inhibitors; diuretics; β-blockers; Thiazide diuretics; dihydropyridine calcium-channel blockers; angiotensin-converting enzyme inhibitors; angiotensin receptor blockers; calcium-channel blockers; thiazide-like diuretics; lisinopril; Edarbyclor; azilsartan medoxomil; chlorthalidone; hydrochlorothiazide; aliskiren; ARB; enalapril; non-steroidalanti-inflammatory drugs; antihypertensive treatment; Chlorthalidone; loop diuretics; angiotensin-converting enzyme inhibitor; angiotensin receptor blocker; statin; captopril; tiopronin; active form of dalcetrapib; active metabolite of prasugrel, R-138727; Liuwei Dihuang pills; metformin hydrochloride sustained-release tablets; irbesartan tablets; renin-angiotensin-aldosterone system inhibitor; type 1 angiotensin II receptor blockade; olmesartan; steroid; immunosuppressive agents; enalapril; corticosteroid treatment; Angiotensin-converting-enzyme inhibitors; antihypertensives; GLP-1 receptor analogue; SGLT2-inhibitor; sacubitril/valsartan; valsartan; Sulodexide; liraglutide; enalapril; ACE-I/ARBs; angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers; labetalol; ACEi; ARB; ARBs | Details |
| 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 |