Bioactivity Comments

The interaction table below provides data from whole cell assays and gives the antiparasite activity of MMV030084 against a number of Plasmodium lifecycle stages. During the asexual blood stages the compound may act as an egress inhibitor, with high activity against synchronized schizonts but minimal activity against rings and trophozoites [1]. MMV030084 does not display activity against either early or late stage gametocytes (IC50 values > 40μM) but does inhibit male gamete exflagellation.

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 cGMP-dependent protein kinase Pf Plasmodium falciparum P. falciparum (Pf) is one of five protozoan parasite species of the genus Plasmodium that cause malaria in humans. Pf is responsible for the majority of malaria related deaths and is the most prevalent species in sub-Saharan Africa. ✖ None Inhibition 9.4 pIC50 - 1 ⤷ pIC50 9.4 (IC50 4x10-10 M) [1] Description: Kinase inhibition assay using recombinant PfPKG

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 cGMP-dependent protein kinase 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 - - 7.0 pIC50 - 1 ⤷ pIC50 7.0 (IC50 1.09x10-7 M) 72 hour growth inhibition assay [1] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) Plasmodium falciparum cGMP-dependent protein kinase 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 - - 6.9 pIC50 - 1 ⤷ pIC50 6.9 (IC50 1.2x10-7 M) 72 hour growth inhibition assay [1] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) Plasmodium falciparum cGMP-dependent protein kinase 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 exflagellation assay - - 6.8 pIC50 - 1 ⤷ pIC50 6.8 (IC50 1.41x10-7 M) Dual Gamete Formation Assay (DGFA): male gamete exflagellation was inhibited in the presence of MMV030084, but not when the compound was washed out prior to gamete formation. Activity against female gametes was not clearly identified [1] Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite) Plasmodium falciparum cGMP-dependent protein kinase 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 - - 6.7 pIC50 - 1 ⤷ pIC50 6.7 (IC50 1.99x10-7 M) Luciferase bioluminescence assay to measure sporozoite invasion into HepG2 liver cells (prophylactic activity) [1] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite)