Identification of Inhibitors of Plasmodium falciparum hexokinase (PfHK)

National Center For Advancing Translational Sciences

Investigators

Linked publications & trials

Abstract

During this period, the NCGC built on the previous LOPAC1280 work by expanding screening to over 55,000 compounds . Confirmed hits were validated and tested in secondary assays to confirm activity. The most potent inhibitors had IC50 values as low as 1 M and several were found to have low micromolar EC50 values against asexual intraerythrocytic stage P. falciparum parasites. These molecules additionally demonstrated limited toxicity against a panel of mammalian cells. As a center, the NCGC has fostered and maintained over 110 active collaborations with both NIH and extramural investigators, facilitating drug discovery efforts across the entire spectrum of human disease. These efforts have led to dozens of high-throughput screens and a number of medicinal chemistry campaigns to further improve on screening hits, providing our collaborators and the general research community with publications and a variety of promising small molecule probes and leads. In addition, the NCGC has worked to advance a number of informatic initiatives to make better use of existing drug and disease target information and provide the general public with easily accessible resources, further catalyzing the development of new therapies for human disease.