KDU691 is an antimalarial compound.1 It inhibits recombinant P. vivax phosphatidylinositol 4-kinase (PI4K) with an IC50 value of 1.5 nM. KDU691 is selective for P. vivax PI4K over recombinant human PI4KβIII and PI3Kα, -β, -?, and -δ (IC50s = 7.9, 8.8, 2.4, 8, and 3.4 ?M, respectively), as well as VPS34 (IC50 = >9.7 ?M) and 36 additional kinases in a panel of lipid and protein kinases (IC50s = >10 ?M). It is active against P. falciparum and P. yoelii schizonts (IC50s = 0.06 and 0.04 ?M, respectively), as well as P. cynomolgi schizonts and hypnozoites (IC50s = 0.11 and 0.2 ?M, respectively).2 KDU691 completely prevents, but does not eradicate established, P. cynomolgi infection in rhesus monkeys when administered at a dose of 20 mg/kg.3
1.McNamara, C.W., Lee, M.C., Lim, C.S., et al.Targeting Plasmodium phosphatidylinositol 4-kinase to eliminate malariaNature504(7479)248-253(2013) 2.Zou, B., Nagle, A., Chatterjee, A.K., et al.Lead optimization of imidazopyrazines: a new class of antimalarial with activity on Plasmodium liver stagesACS Med. Chem. Lett.5(8)947-950(2014) 3.Zeeman, A.M., Lakshminarayana, S.B., van der Werff, N., et al.PI4 kinase is a prophylactic but not radical curative target in Plasmodium vivax-type malaria parasitesAntimicrob. Agents Chemother.60(5)2858-2863(2016)