KDU691

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, -ɣ, and -δ (IC₅₀s = 7.9, 8.8, 2.4, 8, and 3.4 µM, respectively), as well as VPS34 (IC₅₀ = >9.7 µM) and 36 additional kinases in a panel of lipid and protein kinases (IC₅₀s = >10 µM). It is active against P. falciparum and P. yoelii schizonts (IC₅₀s = 0.06 and 0.04 µM, respectively), as well as P. cynomolgi schizonts and hypnozoites (IC₅₀s = 0.11 and 0.2 µM, 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

WARNING This product is not for human or veterinary use.

1. McNamara, C.W., Lee, M.C., Lim, C.S., et al. Targeting Plasmodium phosphatidylinositol 4-kinase to eliminate malaria. Nature 504(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 stages. ACS 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 parasites. Antimicrob. Agents Chemother. 60(5), 2858-2863 (2016).