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The requirement for next-generation antimalarials to be both curative and transmission-blocking necessitates the identification of previously undiscovered druggable molecular pathways. We identified a selective inhibitor of the Plasmodium falciparum protein kinase PfCLK3, which we used in combination with chemogenetics to validate PfCLK3 as a drug target acting at multiple parasite life stages. Consistent with a role for PfCLK3 in RNA splicing, inhibition resulted in the down-regulation of more than 400 essential parasite genes. Inhibition of PfCLK3 mediated rapid killing of asexual liver- and blood-stage P. falciparum and blockade of gametocyte development, thereby preventing transmission, and also showed parasiticidal activity against P. berghei and P. knowlesi Hence, our data establish PfCLK3 as a target for drugs, with the potential to offer a cure-to be prophylactic and transmission blocking in malaria.

Original publication




Journal article


Science (New York, N.Y.)

Publication Date





Wellcome Centre for Integrative Parasitology, University of Glasgow, Glasgow G12 8QQ, UK.


Animals, Mice, Inbred BALB C, Mice, Plasmodium falciparum, Protein-Serine-Threonine Kinases, Protozoan Proteins, Protein Kinase Inhibitors, Antimalarials, Gametogenesis, RNA Splicing, Protein-Tyrosine Kinases, Small Molecule Libraries, High-Throughput Screening Assays, Molecular Targeted Therapy