Protein kinases as targets for antimalarial intervention: Kinomics, structure-based design, transmission-blockade, and targeting host cell enzymes.
The surge of interest in protein kinases as targets for chemotherapeutic intervention in a number of diseases such as cancer and neurodegenerative disorders has stimulated research aimed at determining whether enzymes of this class might also be considered as targets in the context of diseases caused by parasitic protists. Here, we present an overview of recent developments in this field, concentrating (i) on the benefits gained from the availability of genomic databases for a number of parasitic protozoa, (ii) on the emerging field of structure-aided design of inhibitors targeting protein kinases of parasitic protists, (iii) on the concept known as transmission-blockade, whereby kinases implicated in the development of the parasite in their arthropod vector might be targeted to interfere with disease transmission, and (iv) on the possibility of controlling parasitic diseases through the inhibition of host cell protein kinases that are required for the establishment of infection by the parasites.
Doerig
Christian
C
INSERM U609, Wellcome Centre for Molecular Parasitology, University of Glasgow, 120 Glasgow University Place, Glasgow G12 8TA, Scotland, UK. cdoer001@udcf.gla.ac.uk
Billker
Oliver
O
Pratt
David
D
Endicott
Jane
J
D000818:Animals; D000962:Antimalarials / Q000378:metabolism* / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology; D016213:Cyclins / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D008018:Life Cycle Stages; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000378:metabolism; D008954:Models, Biological; D008957:Models, Genetic; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D011494:Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D015800:Protozoan Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship
D000962:Antimalarials; D000981:Antiprotozoal Agents; D016213:Cyclins; C406811:PfPK5 protein, Plasmodium falciparum; D047428:Protein Kinase Inhibitors; D015800:Protozoan Proteins; D011494:Protein Kinases