SKU: K006  / 
    CAS Number: 65277-42-1

    Ketoconazole

    R$876.68 - R$3,801.85

    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.
    Molecular Formula C26H28Cl2N4O4
    References

    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

    Heeres J, Backx LJ, Mostmans JH, Van Cutsem J (1979)  Antimycotic imidazoles. Part 4. Synthesis and antifungal activity of Ketoconazole, a new potent orally active broad-spectrum antifungal agent. J. Med. Chem. 22(8):1003-1005  PMID 490531

    Morsy MA, Sultan SM, Dafalla H (2009)  Electron paramagnetic resonance method for the quantitative assay of Ketoconazole in pharmaceutical preparations. Anal. Chem. 81(16):6991-6995  PMID 20337383

    Nardone PA, Slotman GJ, Vezeridis MP (1988)  Ketoconazole: a thromboxane synthetase and 5-lipoxygenase inhibitor with antimetastatic activity in B16-F10 melanoma. J. Surg. Res. 44(4):425-429 PMID 3361885

    Rice LB and Ghannoum MA (1999)  Antifungal Agents: Mode of action, mechanisms of resistance, and correlation of these mechanisms with bacterial resistance. Clin. Microbiol. Rev. 12(4):501-517  PMID 10515900  

    Van Tyle JH (1984)  Ketoconazole. Mechanism of action, spectrum of activity, pharmacokinetics, drug interactions, adverse reactions and therapeutic Use. Pharmacother. 4(6):343-373  PMID 6151171