High-throughput matrix screening identifies synergistic and antagonistic antimalarial drug combinations.
作者： Bryan T. Mott , Richard T. Eastman , Rajarshi Guha , Katy S. Sherlach , Amila Siriwardana
DOI: 10.1038/SREP13891
关键词:
摘要: Drug resistance in Plasmodium parasites is a constant threat. Novel therapeutics, especially new drug combinations, must be identified at faster rate. In response to the urgent need for antimalarial combinations we screened large collection of approved and investigational drugs, tested 13,910 pairs, many promising combinations. The activity known regimens was confirmed myriad classes positively interacting pairings were discovered. Network clustering analyses reinforced established mechanistic relationships several novel hypotheses. From eleven screens comprising >4,600 per parasite strain (including duplicates) further investigated interactions between antimalarials, calcium homeostasis modulators, inhibitors phosphatidylinositide 3-kinases (PI3K) mammalian target rapamycin (mTOR). These studies highlight important targets pathways provide leads clinically actionable therapy.
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