CHMFL-PI4K-127

CHMFL-PI4K-127 (compound 15g) is an orally active, potent and high selective PfPI4K (Plasmodium falciparum PI4K kinase) inhibitor, with an IC50 of 0.9 nM. CHMFL-PI4K-127 exhibits potent activity against 3D7 Plasmodium falciparum, with an EC50 of 25.1 nM. CHMFL-PI4K-127 shows antimalaria efficacy[1].

Research Areas >> Infection

Signaling Pathways >> PI3K/Akt/mTOR >> PI3K

Signaling Pathways >> PI3K/Akt/mTOR >> PI4K

PI4K:0.9 ± 0.1 nM (IC50)

PI3Kδ:104 ± 3 nM (IC50)

PI3Kα:191 ± 36 nM (IC50)

PI3Kγ:324 ± 19 nM (IC50)

PI3Kβ:392 ± 27 nM (IC50)

Vps34:681 ± 25 nM (IC50)

CHMFL-PI4K-127 (compound 15g) displays high selectivity against PfPI4K over human lipid and protein kinase[1]. CHMFL-PI4K-127 exhibits EC50 values of 23–47 nM against a panel of the drug-resistant strains of P. falciparum[1].

CHMFL-PI4K-127 (compound 15g) (Orally; 0-80 mg/kg/day for 7 days; 0-15 mg/kg, once) exhibits the antimalaria efficacy in both blood stage (80 mg/kg) and liver stage (1 mg/kg) of Plasmodium in infected rodent model[1]. Animal Model: Balb/c mice were infected by P. yoelii[1]. Dosage: 0, 60, 80 mg/kg Administration: Orally, daily for 7 days Result: Displayed significant in vivo antimalarial activities in a dose-dependent manner and 80 mg/kg × 7 days treatment generated curative effects. The 60 mg/kg dosage resulted in suppressive effects during the drug treatment but relapsed after stopping treatment. Animal Model: Balb/c mice were infected by P. yoelii[1]. Dosage: 0, 1, 5, 15 mg/kg Administration: Orally, once Result: Provided the full protection and cure at 1 mg/kg with no negligible parasite visible in the liver of all tested mice at 24, 48, 72, 96, 144 and 196 h, indicating true causal prophylactic efficacy.

[1]. 6'-chloro-N-methyl-5'-(phenylsulfonamido)-[3,3'-bipyridine]-5-carboxamide (CHMFL-PI4K-127) as a novel Plasmodium falciparum PI(4)K inhibitor with potent antimalarial activity against both blood and liver stages of Plasmodium. Eur J Med Chem. 2020 Feb 15;188:112012.