Purfalcamine

Purfalcamine is an orally active, selective Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1) inhibitor with an IC₅₀ of 17 nM and an EC₅₀ of 230 nM. Purfalcamine has antimalarial activity and causes malaria parasites developmental arrest at the schizont stage^[1][2]. In Vitro: Purfalcamine has low activity against Toxoplasma gondii calcium-dependent protein kinase 3 (TgCDPK3)^[1].
Purfalcamine (225, 450 nM) has no effect on the parasitemia in the first 32 hours. After about 40 hours, parasite level remains stable and then begins dropping^[1].
Purfalcamine inhibits proliferation with EC₅₀s of 171-259 nM for P. falciparum strains (3D7, Dd2, FCB, HB3 and W2), which indicates effectiveness against drug-resistant parasites^[1].
Given that the EC₅₀ value for P. falciparum (3D7) is 230 nM, Purfalcamine shows a therapeutic window ranging from 23-fold to 36-fold (EC₅₀s for CHO=12.33 μM, HEp2=7.235 μM, HeLa=7.029 μM and Huh7=5.476 μM)^[1].
In Vivo: Purfalcamine (10 mg/kg; oral gavage; BID; for 6 days) demonstrates a delay in the onset of parasitemia in treated mice^[1].
Purfalcamine (20 mg/kg; orally gavage) exhibits a C_max of 2.6 μM with a half-life of 3.1 hours^[1].