Bioactivity Comments

The antiparasite activity of compound 34c against the asexual blood stage and liver stage of the Plasmodium lifecycle is provided in the interaction table below. For the asexual blood stage evaluation, a panel of culture-adapted P. falciparum strains was used with no evidence of reduced potency against drug resistant strains.

Selectivity at other protein targets
Key to terms and symbols	Click on species/strain names for details	Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference Plasmodium falciparum N-myristoyltransferase Pf3D7 Plasmodium falciparum 3D7 P. falciparum strain 3D7 (Pf3D7) was derived from isolate NF54 by limiting dilution. The complete genome of Pf3D7 has been sequenced (GenBank: LN999946.1). Pf3D7 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is sensitive to a panel of antimalarial compounds including chloroquine and pyrimethamine. ✖ Inhibitor Inhibition 8.1 pKi - 2 ⤷ pKi 8.1 (Ki 8x10-9 M) [2] Description: Enzyme inhibition assay

Whole organism assay data
Key to terms and symbols	Click on species/strain names for details	Click column headers to sort
MOA/likely target Sp. Assay description Type Action Value Parameter Concentration range (M) Reference Plasmodium falciparum N-myristoyltransferase PfNF54 Plasmodium falciparum NF54 P. falciparum strain NF54 (PfNF54) was derived from a patient who had never left the Netherlands. PfNF54 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is sensitive to a panel of antimalarial compounds including chloroquine and pyrimethamine. ✖ Parasite growth inhibition assay - - 6.6 pEC50 - 2 ⤷ pEC50 6.6 (EC50 2.32x10-7 M) [3H]-hypoxanthine incorporation [2] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) Plasmodium falciparum N-myristoyltransferase Pf3D7 Plasmodium falciparum 3D7 P. falciparum strain 3D7 (Pf3D7) was derived from isolate NF54 by limiting dilution. The complete genome of Pf3D7 has been sequenced (GenBank: LN999946.1). Pf3D7 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is sensitive to a panel of antimalarial compounds including chloroquine and pyrimethamine. ✖ Parasite growth inhibition assay - - 6.5 pEC50 - 2 ⤷ pEC50 6.5 (EC50 3.02x10-7 M) [3H]-hypoxanthine incorporation [2] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) Plasmodium falciparum N-myristoyltransferase PfK1 Plasmodium falciparum K1 P. falciparum strain K1 (PfK1) was isolated in Kanchanaburi, Thailand in 1979. PfK1 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is reported to be a multidrug-resistant strain. ✖ Parasite growth inhibition assay - - 6.5 pEC50 - 2 ⤷ pEC50 6.5 (EC50 3.39x10-7 M) [3H]-hypoxanthine incorporation [2] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) Plasmodium falciparum N-myristoyltransferase Pb Plasmodium berghei P. berghei (Pb) is a malaria parasite that infects mammals other than humans with the natural mammalian host being the thicket rat (G. surdaster) from Central Africa. Pb is used in rodent model studies of malaria. ✖ Parasite liver stage assay - - 6.4 pEC50 - 2 ⤷ pEC50 6.4 (EC50 3.72x10-7 M) Luciferase bioluminescence assay to measure viability of exoerythrocytic forms (EEF) [2] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite) Plasmodium falciparum N-myristoyltransferase PfDd2 Plasmodium falciparum Dd2 P. falciparum strain Dd2 (PfDd2) is a clone derived from PfW2, following continuous culture in mefloquine. PfW2 was cloned from the Indochina III/CDC isolate, originally derived from a Laotian patient who failed chloroquine therapy. PfDd2 can be obtained from the Malaria Research and Reference Reagent Resource Center (MR4) and is reported to be resistant to chloroquine, pyrimethamine and mefloquine. ✖ Parasite growth inhibition assay - - 6.0 pEC50 - 2 ⤷ pEC50 6.0 (EC50 9.16x10-7 M) [3H]-hypoxanthine incorporation [2] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)