UCT943, a Next-Generation Plasmodium falciparum PI4K Inhibitor Preclinical Candidate for the Treatment of Malaria
Brunschwig C., Lawrence N., Taylor D., Abay E., Njoroge M., Basarab GS., Le Manach C., Paquet T., Cabrera DG., Nchinda AT., de Kock C., Wiesner L., Denti P., Waterson D., Blasco B., Leroy D., Witty MJ., Donini C., Duffy J., Wittlin S., White KL., Charman SA., Jiménez-Díaz MB., Angulo-Barturen I., Herreros E., Gamo FJ., Rochford R., Mancama D., Coetzer TL., van der Watt ME., Reader J., Birkholtz L-M., Marsh KC., Solapure SM., Burke JE., McPhail JA., Vanaerschot M., Fidock DA., Fish PV., Siegl P., Smith DA., Wirjanata G., Noviyanti R., Price RN., Marfurt J., Silue KD., Street LJ., Chibale K.
The 2-aminopyridine MMV048 was the first drug candidate inhibiting Plasmodium phosphatidylinositol 4-kinase (PI4K), a novel drug target for malaria, to enter clinical development. In an effort to identify the next generation of PI4K inhibitors, the series was optimized to improve properties such as solubility and antiplasmodial potency across the parasite life cycle, leading to the 2-aminopyrazine UCT943.