Gene and Protein Information
Species	TM	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Plasmodium falciparum 3D7	-	575		cPheRS	phenylalanine--tRNA ligase alpha subunit
Gene and Protein Information Comments
The phenylalanyl-tRNA synthetases (FRSs) are unique within the aaRS family because the P. falciparum genome contains four genes that encode three distinct FRSs: cytosolic (heterodimeric cFRS; the α-subunit, described here; β-subunit, PF3D7_1104000), apicoplast (PF3D7_1232000), and mitochondrial FRS (PF3D7_0603700) [1,4].

Previous and Unofficial Names

Pf3D7_01_v3:380,254..382,568(+) | PfcPheRS | PFA0480w | Plasmodium falciparum phenylalanine--tRNA ligase alpha subunit

Database Links
Alphafold	Q8I246 (Pf3D7)
PlasmoDB	PF3D7_0109800 (Pf3D7)
UniProtKB	Q8I246 (Pf3D7)

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Inhibitors
Key to terms and symbols	View all chemical structures	Click column headers to sort
Ligand Sp. Action Value Parameter Reference BRD7929 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 7.6 pIC50 3 ⤷ pIC50 7.6 (IC50 2.3x10-8 M) [3] BRD3444 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 7.3 pIC50 3 ⤷ pIC50 7.3 (IC50 4.6x10-8 M) [3]

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 BRD3444 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 - - 8.1 pEC50 3 ⤷ pEC50 8.1 (EC50 9x10-9 M) SYBR Green I assay [3] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) BRD7929 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 - - 8.1 pEC50 3 ⤷ pEC50 8.1 (EC50 9x10-9 M) SYBR Green I assay [3] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) BRD3444 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 - - 6.8 pEC50 3 ⤷ pEC50 6.8 (EC50 1.4x10-7 M) Luciferase bioluminescence assay to measure parasite invasion into HepG2 liver cells [3] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite) BRD7929 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 late stage (IV–V) gametocyte assay - - 6.8 pEC50 3 ⤷ pEC50 6.8 (EC50 1.6x10-7 M) [3] BRD7929 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 - - 6.8 pEC50 3 ⤷ pEC50 6.8 (EC50 1.62x10-7 M) Luciferase bioluminescence assay to measure parasite invasion into HepG2 liver cells [3] Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite) BRD3444 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 late stage (IV–V) gametocyte assay - - 6.2 pEC50 3 ⤷ pEC50 6.2 (EC50 6.63x10-7 M) [3] Lifecycle stages: Plasmodium sexual blood stage (gametocyte)

Malaria Pharmacology Comments

The three PfFRSs are class II aaRSs [1]. The aaRSs are emerging targets for antimalarial agents (reviewed in [4]), with PfcFRS the first member of the family whose inhibition results in elimination of asexual blood, liver and transmission-stage parasites [3]. PfcFRS is ranked as a "High Priority" target in the Malaria Drug Accelerator (MalDA) portfolio [2].