10.1021/cb100399x.s001
Bonnie K. Baxter
Bonnie K.
Baxter
Louis DiDone
Louis
DiDone
Duana Ogu
Duana
Ogu
Stanford Schor
Stanford
Schor
Damian J. Krysan
Damian J.
Krysan
Identification, <i>in Vitro</i> Activity and Mode of Action of Phosphoinositide-Dependent-1 Kinase Inhibitors as Antifungal Molecules
American Chemical Society
2011
Pkh kinases
Antifungal MoleculesAlthough protein kinases
protein kinase inhibitors
cell wall stress response
OSU
antifungal drug development
yeast
molecule
UCN
PDK 1 orthologs
KP
2011-05-20 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Identification_i_in_Vitro_i_Activity_and_Mode_of_Action_of_Phosphoinositide_Dependent_1_Kinase_Inhibitors_as_Antifungal_Molecules/2649793
Although protein kinases have recently emerged as important drug targets, the anti-infective potential of protein kinase inhibitors has not been developed extensively. We identified the mammalian PDK1 inhibitor KP-372-1 as a potent antifungal molecule with activity against yeast and fungal biofilms using a screening strategy for protein kinase inhibitors that block the cell wall stress response in yeast. Genetic and biochemical studies indicate that KP-372-1 inhibits fungal PDK1 orthologs (Pkh kinases) as part of its mode of action and support a role for Pkh kinases in eisosome assembly. Two other structurally distinct molecules that inhibit PDK1, OSU-03012 and UCN-01, also have antifungal activity. Taken together, these data indicate that fungal PDK1 orthologs are promising targets for new antifungal drug development.