Antimalarial drug discovery: targeting protein kinases.
Protein kinases (PKs) are prime targets for drug discovery in a variety of diseases, including cancer and neurodegenerative pathologies. The characterisation of the kinome of the human malaria parasite Plasmodium falciparum has revealed profound divergences, at several levels, between PKs of the parasite and those of its host. Here, the authors review the major issues and recent advances regarding the development of Plasmodium-selective PK inhibitors, with emphasis on target identification and validation, and on structure-based design. The authors also discuss the possibility of interfering with: i) Plasmodium PKs regulating transmission to the mosquito vector; and ii) host PKs that may be required for parasite survival.
Doerig
Christian
C
INSERM U609, Wellcome Centre for Molecular Parasitology, Biomedical Research Centre, University of Glasgow, 120 University Place, Glasgow, UK. cdoer001@udcf.gla.ac.uk
Meijer
Laurent
L
D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D015195:Drug Design; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D010802:Phylogeny; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism
D000962:Antimalarials; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases