Ketoconazole is an insoluble azole antimycotic compound that was discovered in 1976 (Janssen Pharmaceuticals) and patented in 1977. It is a racemic mixture of the two enantiomers: levoketoconazole and dextroketoconazole. It is a bioactive small molecule acting as a protein inhibitor, specifically inhibiting CYP3A5 involved in P-450-dependent steroid biosynthesis. The compound has antineoplastic activity.
Ketoconazole is soluble in DMSO, ethanol, chloroform, and methanol.
This product is considered a dangerous good. Quantities above 1 gram may be subject to additional shipping fees.
|Mechanism of Action||Ketoconazole increases cell permeability by inhibiting enzymes involved in ergosterol synthesis, specifically the enzyme P450 14 alpha-demethylase (CYP51A1) which converts lanosterol to ergosterol. The increased permeability has a toxic effect on the fungi and leads to cell death.|
|Microbiology Applications||Resistance to Ketoconazole has been observed in a number of clinical fungal isolates, including Candida albicans. Resistance arises as a result of mutations in the sterol biosynthesis pathway. Multidrug-resistance (MDR) genes can also play a role in reducing the cellular levels of the compound.|
|Cancer Research Applications||Ketoconazole was tested on hepatocellular carcinoma cells, cell-line-derived xenografts, and a xenograft (PDX) model. It induced mitophagy both in vitro and in vivo via downregulation of cyclooxygenase-2 to induce apoptosis. This supports a novel link between Ketoconazole and mitophagy machinery for cancer research applications (Chen et al, 2019).|
|Spectrum||Ketoconazole is a broad spectrum antifungal agent targeting a wide variety of fungal cell membranes.|
Chen Y et al (2019) Ketoconazole exacerbates mitophagy to induce apoptosis by downregulating cyclooxygenase-2 in hepatocellular carcinoma. J. Hepatol. 70(1):66-77 PMID 30287340
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