Plasmodium malaria remains a tremendous public health burden. In order to sustain recent progress in decreasing malaria related morbidity and mortality further progress in development of antimalarials with potential to interrupt disease transmission are required. To identify lead development candidates as well as novel biological pathways essential for parasite transmission to the mosquito vector NCGC scientists have optimized and miniaturized the novel fertilization assay to 1536-well format, providing the opportunity to conduct high-throughput evaluation of compounds against early mosquito stages. Initial studies have already screened the Mechanism of Interrogation PlatE (MIPE) compound library, with 2,480 small molecules with annotated mechanisms of action, identifying 135 compounds that inhibited fertilization with IC50s under 2 M. Work is proceeding with validating these hits as well as screening approved drug collections for repurposing efforts.