title: Plasmodium kinases as targets for new-generation antimalarials.
abstract: There is an urgent need for the development of new antimalarial drugs with novel modes of actions. The malarial parasite, Plasmodium falciparum, has a relatively small kinome of <100 kinases, with many members exhibiting a high degree of structural divergence from their host counterparts. A number of Plasmodium kinases have recently been shown by reverse genetics to be essential for various parts of the complex parasitic life cycle, and are thus genetically validated as potential targets. Implementation of mass spectrometry-based phosphoproteomics approaches has informed on key phospho-signalling pathways in the parasite. In addition, global phenotypic screens have revealed a large number of putative protein kinase inhibitors with antimalarial potency. Taken together, these investigations point to the Plasmodium kinome as a rich source of potential new targets. In this review, we highlight recent progress made towards this goal.
authors.affiliation: Department of Biochemistry & Molecular Biology, School of Biomedical Sciences, Monash University, Wellington Road, Clayton VIC, 3800, Australia. isabelle.lucet@monash.edu
authors.forename: Isabelle S
authors.initials: IS
authors.lastname: Lucet
authors.forename: Andrew
authors.initials: A
authors.lastname: Tobin
authors.forename: David
authors.initials: D
authors.lastname: Drewry
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Wilks
authors.forename: Christian
authors.initials: C
authors.lastname: Doerig
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D008958:Models, Molecular; D058990:Molecular Targeted Therapy / Q000379:methods; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology*; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism; D040901:Proteomics / Q000379:methods
chemical_list: D000962:Antimalarials; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases