Transmission blocking inhibitors of Malaria

疟疾仍然是一个巨大的公共卫生负担。为了维持最近在减少疟疾相关发病率和死亡率方面取得的进展，需要在开发有可能阻断疾病传播的抗疟疾药物方面取得进一步进展。为了确定铅开发候选对象以及寄生虫传播到蚊子媒介NCGC所必需的新生物途径，科学家们优化并缩小了新的受精检测方法，使其达到1536孔的格式，从而提供了对化合物进行高通量评估以对抗早期蚊子阶段的机会。初步研究已经筛选了询问板机制(MIPE)化合物文库，包含2,480个带有注释作用机制的小分子，鉴定了135个化合物，用2微米以下的IC50抑制受精。验证这些命中的工作正在进行中，以及筛选经批准的药物集合以进行再利用努力。

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 uM. Work is proceeding with validating these hits as well as screening approved drug collections for repurposing efforts.