Enabling Malarial Kinome Directed Drug Discovery

DESCRIPTION (provided by applicant): World Health Organization (WHO) estimates that there are 154-289 million cases of malaria and 610,000-971,000 deaths each year. Malaria is caused by a protozoan parasite, Plasmodium, which is transmitted through the bite of a mosquito. In the absence of an effective vaccine against Malaria, chemotherapy remains the only viable treatment option. However with emerging reports of acquired resistance against antifolates and chloroquine, and more recently artemisinin, there is an urgent need for new drugs and drug targets. The genome of Plasmodium falciparum, the species responsible for most mortality, has been sequenced and is predicted to encode 86-99 kinases. Recent high throughput screening efforts of large compound libraries have identified numerous potent hits, which have chemotypes reminiscent of kinase inhibitors. However, the lack of commercially available robust kinase assays has hindered Plasmodium kinome-directed drug discovery. In this application, we aim to d