Plasmodium falciparum phosphatidylinositol 4-kinase

Target id: 2972

Nomenclature: Plasmodium falciparum phosphatidylinositol 4-kinase

Abbreviated Name: PfPI4K

Family: Antimalarial targets

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for Plasmodium falciparum phosphatidylinositol 4-kinase in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Plasmodium falciparum 3D7 - 1559 PI4K phosphatidylinositol 4-kinase
Database Links
UniProtKB
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
MMV048 Pf Binding 6.5 – 7.0 pKd 2
pKd 7.0 (Kd 1x10-7 M) [2]
pKd 6.5 (Kd 3x10-7 M) [2]
Whole Organism Assay Data Linked to This Target
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Ligand Sp. Assay description Type Action Affinity Units Reference
MMV048 PfNF54 Parasite growth inhibition assay - - 7.6 pIC50 2
pIC50 7.6 (IC50 2.8x10-8 M) [3H]-hypoxanthine incorporation assay [2]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
MMV048 Pf Standard membrane feeding assay (SMFA) - - 6.9 pIC50 2
pIC50 6.9 (IC50 1.11x10-7 M) Indirect SMFA [2]
Lifecycle stages: Plasmodium mosquito host stage (gametocyte, zygote, ookinete, oocyst, sporozoite)
MMV048 PfNF54 Parasite gametocyte viability assay - - 6.6 – 6.8 pIC50 2
pIC50 6.8 (IC50 1.4x10-7 M) Parasite late stage (IV-V) gametocyte assay using luciferase reporter line [2]
Lifecycle stages: Plasmodium sexual blood stage (gametocyte)
pIC50 6.7 (IC50 2.14x10-7 M) Parasite early stage (I-III) gametocyte assay using luciferase reporter line [2]
Lifecycle stages: Plasmodium sexual blood stage (gametocyte)
pIC50 6.6 (IC50 2.85x10-7 M) Parasite late stage (IV-V) gametocyte assay: parasitic lactate dehydrogenase (pLDH) assay [2]
Lifecycle stages: Plasmodium sexual blood stage (gametocyte)
MMV048 Pc Parasite liver stage assay - - 5.0 – 7.2 pIC50 2
pIC50 7.2 (IC50 6.1x10-8 M) P. cynomolgi assay to assess inhibition of liver stage development (prophylactic activity) [2]
Lifecycle stages: Plasmodium dormant liver stage (hypnozoite)
pIC50 7.2 (IC50 6.4x10-8 M) P. cynomolgi assay to assess inhibition of liver stage development (prophylactic activity) [2]
Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite)
pIC50 <5.0 (IC50 >1x10-5 M) P. cynomolgi assay to assess elimination of hypnozoites (potential as a radical cure) [2]
Lifecycle stages: Plasmodium dormant liver stage (hypnozoite)
General Comments
The Plasmodium lipid kinase, phosphatidylinositol-4 kinase (PfPI4K), was first identified as the target of the imidazopyrazines, a novel class of experimental antimalarial compounds that have been shown to be active in multiple Plasmodium spp. and at each stage of malaria infection in the vertebrate host [1]. This study also reported that the imidazopyrazines act through inhibitory interaction with the ATP-binding pocket of the kinase and proposed that PfPI4K acts at the Golgi to regulate essential membrane trafficking events.

References

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1. McNamara CW, Lee MC, Lim CS, Lim SH, Roland J, Simon O, Yeung BK, Chatterjee AK, McCormack SL, Manary MJ et al.. (2013) Targeting Plasmodium PI(4)K to eliminate malaria. Nature, 504 (7479): 248-253. [PMID:24284631]

2. Paquet T, Le Manach C, Cabrera DG, Younis Y, Henrich PP, Abraham TS, Lee MCS, Basak R, Ghidelli-Disse S, Lafuente-Monasterio MJ et al.. (2017) Antimalarial efficacy of MMV390048, an inhibitor of Plasmodium phosphatidylinositol 4-kinase. Sci Transl Med, 9 (387). [PMID:28446690]

How to cite this page

Antimalarial targets: Plasmodium falciparum phosphatidylinositol 4-kinase. Last modified on 25/04/2018. Accessed on 20/07/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2972.