Ketoconazole binds to the intracellular corticosteroid-binding protein in Candida albicans.

Ketoconazole is a broad-spectrum, orally-active antifungal agent that has been shown to inhibit sterol synthesis in susceptible fungi. We have previously demonstrated the presence of an intracellular protein in several Candida species that binds mammalian corticosteroids with high affinity. In this paper we report that ketoconazole competitively displaces [3H]corticosterone from the Candida corticosteroid-binding protein at concentrations readily achieved in therapeutic settings. Ketoconazole was at least 50-100 times more potent than structurally related imidazole compounds. Additional data suggest, however, that the binding of ketoconazole and related drugs to this Candida protein is not critical for the in vitro antifungal activity of these drugs.