UCT943 is a next-generation Plasmodium falciparum PI4K inhibitor. UCT943 inhibits the P. vivax PI4K ( Pv PI4K) enzyme with an IC 50 of 23 nM
In Vitro
UCT943 maintains high in vitro selectivity (>200-fold) for the parasite Pv PI4K versus the human PI4Kβ isozyme (IC 50 of PI4Kβ, 5.4 μM), inhibition of which is linked to immunosuppressive effects. In vitro cytotoxicity of UCT943 is tested against L6 cells, chinese hamster ovarian (CHO), Vero, and HepG2 cells, with 50% cytotoxic concentrations (CC 50 s) of 12, 17, 113, and 13 μM, respectively. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
UCT943 shows excellent in vivo efficacy in the Plasmodium berghei (10 mg/kg and 3 mg/kg; oral administration; daily; 4 days) and P. falciparum NSG (NOD- scid IL-2Rγ ) mouse models (0.01, 0.1, 0.3, 1.1 and 10 mg/kg; oral administration; once per day; 4 days). When dosed at 10 mg/kg per os (p.o.), UCT943 reduces parasitemia by >99.9% in the mouse P. berghei infection model and cures all mice, with >30 mean survival days (MSD). At 3 mg/kg p.o., no complete cure is achieved, and MSD is 10 days, albeit parasitemia is reduced by 99%. The resulting 90% effective dose (ED 90 ) is 1.0 mg/kg p.o. in the P. berghei infection model. The ED 90 is 0.25 mg/kg in the P. falciparum -infected NSG mouse model . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Mice with P. berghei and P. falciparum NOD- scid IL-2Rγ (NSG) models Dosage: 10 mg/kg and 3 mg/kg for P. berghei model; 0.01, 0.1, 0.3, 1.1 and 10 mg/kg for P. falciparum NOD- scid IL-2Rγ (NSG) model Administration: Oral administration; daily; 4 days for P. berghei model Oral administration; once per day; 4 days for P. falciparum NOD- scid IL-2Rγ (NSG) model Result: The ED 90 is 1.0 mg/kg in the P. berghei infection model. The ED 90 is 0.25 mg/kg in the P. falciparum -infected NSG mouse model.
IC50& Target:Pv PI4K 23 nM (IC 50 ) Plasmodium
Associated Targets
KCNH2Tclin Potassium voltage-gated channel subfamily H member 2 1 Activities
