Gene and Protein Information
Species	TM	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Plasmodium falciparum 3D7	-	853		PKG	cGMP-dependent protein kinase

Previous and Unofficial Names

PKG | Pf3D7_14_v3:1,490,321..1,494,453(-) | PF14_0346

Database Links
Alphafold	Q8I719 (Pf3D7)
PlasmoDB	PF3D7_1436600 (Pf3D7)
UniProtKB	Q8I719 (Pf3D7)

Selected 3D Structures
	Description:  Crystal Structure of PF3D7_1436600 PDB Id:  5DYK Resolution:  2.45Å Species:  Plasmodium falciparum References:  3

Other Binding Ligands
Key to terms and symbols		Click column headers to sort
Ligand Sp. Action Value Parameter Reference ML10 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. ✖ Inhibition 9.8 pIC50 2 ⤷ pIC50 9.8 (IC50 1.6x10-10 M) [2] Description: microfluidic mobility shift assay MMV030084 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. ✖ Inhibition 9.4 pIC50 4 ⤷ pIC50 9.4 (IC50 4x10-10 M) [4] Description: Kinase inhibition assay using recombinant PfPKG

Whole Organism Assay Data Linked to This Target
Key to terms and symbols		Click column headers to sort
Ligand Sp. Assay description Type Action Value Parameter Reference ML10 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 - - 8.7 pEC50 2 ⤷ pEC50 8.7 (EC50 2.1x10-9 M) [3H]-hypoxanthine incorporation [2] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) MMV030084 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 4 ⤷ pIC50 7.0 (IC50 1.09x10-7 M) 72 hour growth inhibition assay [4] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) MMV030084 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 4 ⤷ pIC50 6.9 (IC50 1.2x10-7 M) 72 hour growth inhibition assay [4] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) MMV030084 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 4 ⤷ 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 [4] Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite) MMV030084 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 4 ⤷ pIC50 6.7 (IC50 1.99x10-7 M) Luciferase bioluminescence assay to measure sporozoite invasion into HepG2 liver cells (prophylactic activity) [4] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite)

Malaria Pharmacology Comments

The Plasmodium cGMP-dependent protein kinase (PfPKG) is an attractive target for next-generation antimalarials as it has been implicated in multiple cellular activities at various stages of the parasite lifecycle [1]. A medicinal chemistry programme has identified an imidazopyridine series that demonstrates promising activity and may warrant further development [2].