CHMFL-PI4K-127 (compound 15g) is a highly selective inhibitor of PfPI4K (Plasmodium falciparum PI4K kinase) with oral activity (IC50=0.9 nM) and exhibits strong inhibitory activity against Plasmodium falciparum 3D7 (EC50=25.1 nM), demonstrating significant anti-malaria effects.

PI3Kβ:392 ± 27 nM, PI3Kγ:324 ± 19 nM, PI3Kδ:104 ± 3 nM, PI3Kα:191 ± 36 nM, VPS34:681 ± 25 nM, PI4K:0.9 ± 0.1 nM

CHMFL-PI4K-127 (compound 15g) exhibits significant selectivity for PfPI4K over human lipid and protein kinases [1], with effective half-maximal concentration (EC50) values of 23-47 nM against various drug-resistant strains of P. falciparum [1].

CHMFL-PI4K-127 (compound 15g) exhibited significant antimalarial efficacy in both the blood stage (80 mg/kg) and liver stage (1 mg/kg) of Plasmodium infection in a rodent model when administered orally. In Balb/c mice infected with P. yoelii, varying dosages were tested over different periods. For the blood stage, daily doses of 0, 60, and 80 mg/kg for 7 days showed curative effects at 80 mg/kg, while 60 mg/kg resulted in suppressive effects with relapse after cessation. In the liver stage, single doses of 0, 1, 5, and 15 mg/kg showed that a 1 mg/kg dose provided full protection and cure, eliminating visible liver parasites at multiple time points post-treatment, indicating strong causal prophylactic efficacy.