Imaging of Plasmodium liver stages to drive next-generation antimalarial drug discovery

ABSTRACT: Most malaria drug development focuses on parasite stages detected in red-blood cells even though to achieve eradication next-generation drugs active against both erythrocytic and exo-erythrocytic forms would be preferable. We applied a multifactorial approach to a set of >4,000 commercially available compounds with previously demonstrated blood stage activity (IC50 < 1 M-BM-5M), and identified chemical scaffolds with potent activity against both forms. From this screen, we identified an imidazolopiperazine scaffold series that was highly enriched among compounds active against Plasmodium liver stages. Our orally bioavailable lead imidazolopiperazine confers complete causal prophylactic protection (15 mg/kg) in rodent models of malaria and shows potent in vivo blood-stage therapeutic activi

ORGANISM(S): Plasmodium falciparum

SUBMITTER: Elizabeth Winzeler 

PROVIDER: E-GEOD-32485 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress