Maria J. Lafuente-Monasterio

TL;DR: DSM265, a triazolopyrimidine-based inhibitor of the pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase (DHODH), is the first DHODH inhibitor to reach clinical development for treatment of malaria as discussed by the authors.

TL;DR: Oral administration of a single dose of decoquinate effectively prevents the appearance of disease and warrants its exploitation as a potent antimalarial compound.

TL;DR: One chemical subseries was found to exhibit oral activity but contained a labile ester that could not be replaced without loss of activity, and the original hit exhibited remarkable sensitivity to minor structural change.

TL;DR: DSM421 showed excellent efficacy in the SCID mouse model of P. falciparum malaria that supports the prediction of a low human dose (<200 mg), and has the potential to be developed as a single-dose cure or once-weekly chemopreventative for both P. Falcon and P. vivax malaria.

TL;DR: These mutant parasites were often hypersensitive to other PfDHODH inhibitors, which immediately suggested a novel combination therapy approach to preventing resistance, and a combination of wild-type and mutant-type selective inhibitors led to resistance far less often than either drug alone.