Table 1. Level of Validation Achieved for Plasmodium Targets Covered in This Perspectivea.
P. falciparum protein kinase | genetic validationb | phenotypic validationc | in vivo efficacy | clinical validation |
---|---|---|---|---|
CDPK1 | √d | √ | √ | |
CDPK4 | √ | √ | √e | |
PKG | √ | √ | √ | |
PKA | √e | |||
MRK | √ | √ | ||
GSK-3 | √ | √ | ||
NEK-1 | √ | √ | √ | |
FIKK8 | √ | |||
PI3Kf | √ | √ | ||
PI4K | √ | √ | √ | √ |
√ Indicates level of validation was achieved.
Genetic validation of kinases refers to where potential essentiality has been confirmed by knockout, chemical-genetic, or overexpression methods.
The fields are checked if an inhibitor of the kinase target also displayed whole cell activity recognizing that the activity may or may not be due solely to inhibition of the target.
There are conflicting data in the literature as to whether the target has been genetically validated.
Transmission-blocking was shown in an animal model.
DHA, implicated as a PI3K inhibitor, has other modes-of-action that are thought to be primarily responsible for antiplasmodium activity.