Principal Investigator (PI)
The Foundation is providing £165,415 in support.
Dr Maria Penzo
GSK provides expertise and know-how on high throughput screening and post-screening processes, as well as access to key facilities to set-up and perform this work. GSK is providing access to a wider chemical diversity for screening (chemical libraries) and to information about the parasitological and toxicological profile of the promising molecules identified.
David Baker’s laboratory and collaborators have demonstrated in recent years that the malaria parasite cGMP-dependent protein kinases (PKG) has essential roles during a number of stages of its complex life cycle. Specific PKG inhibitors prevent blood stage parasite development by blocking both merozoite egress and invasion. They also block transformation of gametocytes into gametes, ookinete motility in the mosquito as well as late liver stage development. A recent drug discovery partnership between the LSHTM and MRC Technology generated highly potent and selective inhibitors of the malaria parasite PKG with excellent activity against both replicative and transmissible stages. The compounds were active in vivo via the oral route and one of them cleared P. falciparum infection in the GSK SCID model. This project will screen GSK compound libraries to identify new inhibitor scaffolds that target the malaria parasite PKG enzyme with the final aim of developing a drug that can be used to both treat malaria and block transmission.