PI4Kβ-IN-1 is an orally active selective inhibitor of PI4Kβ with an IC50 of 0.9 nM. It exhibits inhibitory activity across all stages of the P. falciparum lifecycle, including the blood, liver, and transmission phases. In mouse models infected with Plasmodium falciparum, PI4Kβ-IN-1 demonstrates significant antimalarial efficacy. This compound is applicable for research on malaria caused by Plasmodium falciparum.

PI4KB:0.9 nM

PI4Kβ-IN-1 (Compound 18) is a potent inhibitor of recombinant Plasmodium vivax phosphatidylinositol-4-kinase IIIβ (PvPI4K) in the presence of ATP, with an IC₅₀ value of 1.2 nM. For Plasmodium falciparum asexual blood stage (ABS) parasites, it exhibits strong antimalarial activity, with IC₅₀ values of 0.024 μM for the NF54 drug-sensitive strain and 0.053 μM for the K1 multidrug-resistant strain. Additionally, PI4Kβ-IN-1 has gameticidal activity against Plasmodium falciparum gametocytes, showing IC₅₀ values of 0.38 μM for immature gametocytes and 0.61 μM for late-stage gametocytes. It inhibits Plasmodium falciparum liver schizonts (IC₅₀ = 0.065 μM) and blocks gamete formation (IC₅₀ = 0.87 μM). PI4Kβ-IN-1 exhibits low cytotoxicity towards mammalian cells, with IC₅₀ values of 30 μM in CHO cells, 18.2 μM in HepG2 cells, and 47.8 μM in L6 cells. Furthermore, it inhibits human ataxia telangiectasia mutated kinase (HsATM) with IC₅₀ values of 2 nM at 10 μM ATP and 103 nM at 500 μM ATP.

PI4Kβ-IN-1 (Compound 18) administrated orally at a dosage of 1-30 mg/kg once daily for four consecutive days, demonstrates potent in vivo antimalarial efficacy in a humanized NOD-scid IL-2Rγnull (NSG) mouse model infected with Plasmodium falciparum Pf3D7 0087/N9.