Last Updated: 20/01/2023
Development of inhibitors of P. falciparum cGMP dependent protein kinase (PfPKG) for malaria chemoprevention
Objectives
To initiate a medicinal chemistry effort to synthesize and test a new chemical series of PfPKG inhibitors.
Malaria is caused by the protozoan parasite, Plasmodium. It begins with the infection by Plasmodium sporozoites of the liver. This step is essential for the expansion of parasite numbers and the subsequent symptomatic erythrocytic cycle. Inhibition of pre-erythrocytic infection will prevent malaria pathology and relapses from P. vivax. Current drugs against pre-erythrocytic stages have significant side-effects or are expensive. Therefore, there is an urgent need for new drugs against pre-erythrocytic stages of Plasmodium. Our scientific premise is that inhibition of P. falciparum cGMP-dependent protein kinase (PfPKG) will block the pre-erythrocytic cycle, and impede the erythrocytic cycle. Our hypothesis is based on data demonstrating that (i) chemical inhibition of PfPKG prevents infection by P. falciparum sporozoites of tissue culture cells, and by P. berghei sporozoites of mice. (ii) Chemical or genetic inhibition of P. berghei PKG blocks development of invaded sporozoites into mature, infectious liver stages.
Article: Overlapping and distinct roles of CDPK family members in the pre-erythrocytic stages of the rodent malaria parasite, Plasmodium bergheiArticle: Plasmodium falciparum Cyclic GMP-Dependent Protein Kinase Interacts with a Subunit of the Parasite Proteasome
Aug 2017 — Jul 2022
$2.1M
Related Resources
