Applications:New structural and mechanistic classes of antifungal therapeutics are needed to improve treatment options and to counter increasing resistance to currently used agents. In addition, there is no effective oral alternatives available to date. This invention identifies and validates the mechanistic characterization of PDK1 inhibitors as novel antifungal agents with potent activity against planktonic and biofilm Candida species and Cryptococcus neoformans. PDK1 is absolutely essential for fungal survival and inhibiting this target results in cell lysis and death.
The inventors show that PDK1 is a novel and effective way to treat fungal infections. These targets represent new structural and mechanism that may have advantages over the present toxic and resistant-laden therapies. In addition these non-intrusive drug candidates that inhibit PDK1 can conveniently be given orally, are well tolerated, and several compounds are available and in the clinic.