Chemical Interrogation of the Malaria Kinome

The cover picture shows small-molecule kinase inhibitors that were identified as antimalarials by using a forward chemical genetic screen. The malaria kinase tree displayed in the center shows parasite kinases that are predicted based on protein-sequence analyses. The background shows the lifecycle of the malaria parasite, which includes a mosquito vector and the infection of human liver cells, followed by invasion of red blood cells. On , E. R. Derbyshire, J. Clardy et al. explain how they completed this screen with a diverse array of kinase inhibitors, including several compounds already in clinical trials for cancer, to discover potential probes to interrogate the malaria kinome. Several different parasite kinases were identified as potential targets from analysis of the screening hits and the work demonstrates that the identified kinases are essential to both liver- and blood-parasite stages, thus highlighting the essential role of kinases to parasite biology. These findings identified small-molecule probes to explore malaria biology as well as show that the malaria kinome is a target rich for disease prevention and treatment.