Top ▲

Plasmodium falciparum phosphatidylinositol 4-kinase beta

Click here for help

Target id: 2972

Nomenclature: Plasmodium falciparum phosphatidylinositol 4-kinase beta

Abbreviated Name: PfPI4Kβ

Family: Kinases (Plasmodium spp.)

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Plasmodium falciparum 3D7 - 1559 PI4KB phosphatidylinositol 4-kinase beta
Gene and Protein Information Comments
Our phosphatidylinositol 4-kinase beta summary page provides information about the closest human orthologue (~43% shared sequence identity).
Previous and Unofficial Names Click here for help
phosphatidylinositol 4-kinase | phosphatidylinositol 4-kinase type III beta | PI4K | PI4KIIIβ | PI4KIIIbeta | PFE0485w
Database Links Click here for help
Alphafold
PlasmoDB
UniProtKB

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
CHMFL-PI4K-127 Small molecule or natural product Guide to Malaria Pharmacology Ligand Pf Inhibition 9.1 pIC50 4
pIC50 9.1 (IC50 9x10-10 M) [4]
NCATS-SM3710 Small molecule or natural product Guide to Malaria Pharmacology Ligand Pf Inhibition 8.7 pIC50 3
pIC50 8.7 (IC50 2x10-9 M) [3]
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
MMV048 Small molecule or natural product Guide to Malaria Pharmacology Ligand Pf Binding 6.5 – 7.0 pKd 6
pKd 7.0 (Kd 1x10-7 M) [6]
pKd 6.5 (Kd 3x10-7 M) [6]
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
NCATS-SM3710 Small molecule or natural product Guide to Malaria Pharmacology Ligand PfNF54 Parasite growth inhibition assay - - 9.4 pEC50 3
pEC50 9.4 (EC50 3.8x10-10 M) Viability measured using MitoProbe DiIC1(5) staining and flow cytometry [3]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
NCATS-SM3710 Small molecule or natural product Guide to Malaria Pharmacology Ligand Pf Parasite late stage (IV–V) gametocyte assay - - 8.2 pEC50 3
pEC50 8.2 (EC50 5.77x10-9 M) Viability measured using MitoProbe DiIC1(5) staining and flow cytometry [3]
Lifecycle stages: Plasmodium sexual blood stage (gametocyte)
CHMFL-PI4K-127 Small molecule or natural product Guide to Malaria Pharmacology Ligand Pf3D7 Parasite growth inhibition assay - - 7.6 pEC50 4
pEC50 7.6 (EC50 2.51x10-8 M) SYBR Green I assay [4]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
CHMFL-PI4K-127 Small molecule or natural product Guide to Malaria Pharmacology Ligand PfDd2 Parasite growth inhibition assay - - 7.5 pEC50 4
pEC50 7.5 (EC50 3.03x10-8 M) SYBR Green I assay [4]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
UCT943 Small molecule or natural product Guide to Malaria Pharmacology Ligand Pb Parasite liver stage assay - - 9.0 pIC50 1
pIC50 9.0 (IC50 9.2x10-10 M) Luciferase bioluminescence assay to measure sporozoite invasion (prophylactic activity) [1]
Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite)
UCT943 Small molecule or natural product Guide to Malaria Pharmacology Ligand PfHB3 Parasite growth inhibition assay - - 8.4 pIC50 1
pIC50 8.4 (IC50 3.7x10-9 M) [3H]-hypoxanthine incorporation [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
UCT943 Small molecule or natural product Guide to Malaria Pharmacology Ligand Pf7G8 Parasite growth inhibition assay - - 8.4 pIC50 1
pIC50 8.4 (IC50 4.1x10-9 M) [3H]-hypoxanthine incorporation [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
UCT943 Small molecule or natural product Guide to Malaria Pharmacology Ligand PfV1/S Parasite growth inhibition assay - - 8.4 pIC50 1
pIC50 8.4 (IC50 4.2x10-9 M) [3H]-hypoxanthine incorporation [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
UCT943 Small molecule or natural product Guide to Malaria Pharmacology Ligand PfK1 Parasite growth inhibition assay - - 8.3 pIC50 1
pIC50 8.3 (IC50 4.7x10-9 M) [3H]-hypoxanthine incorporation [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
UCT943 Small molecule or natural product Guide to Malaria Pharmacology Ligand PfD6 Parasite growth inhibition assay - - 8.3 pIC50 1
pIC50 8.3 (IC50 5.2x10-9 M) [3H]-hypoxanthine incorporation [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
UCT943 Small molecule or natural product Guide to Malaria Pharmacology Ligand PfNF54 Parasite growth inhibition assay - - 8.3 pIC50 1
pIC50 8.3 (IC50 5.4x10-9 M) [3H]-hypoxanthine incorporation [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
UCT943 Small molecule or natural product Guide to Malaria Pharmacology Ligand PfDd2 Parasite growth inhibition assay - - 8.2 pIC50 1
pIC50 8.2 (IC50 5.7x10-9 M) [3H]-hypoxanthine incorporation [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
UCT943 Small molecule or natural product Guide to Malaria Pharmacology Ligand Pc Parasite liver stage assay - - >8.0 pIC50 1
pIC50 >8.0 (IC50 <1x10-8 M) P. cynomolgi assay to assess inhibition of liver stage development (prophylactic activity) [1]
Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite)
MMV048 Small molecule or natural product Guide to Malaria Pharmacology Ligand PfNF54 Parasite growth inhibition assay - - 7.6 pIC50 6
pIC50 7.6 (IC50 2.8x10-8 M) [3H]-hypoxanthine incorporation assay [6]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
KDU691 Small molecule or natural product Guide to Malaria Pharmacology Ligand Pf Parasite growth inhibition assay - - 7.5 pIC50 5
pIC50 7.5 (IC50 2.99x10-8 M) SYBR Green assay [5]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
KDU691 Small molecule or natural product Guide to Malaria Pharmacology Ligand Py Parasite liver stage assay - - 7.4 pIC50 5
pIC50 7.4 (IC50 3.6x10-8 M) Sporozoite hepatocyte invasion assay [5]
Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite)
compound 55 [PMID: 29889526] Small molecule or natural product Guide to Malaria Pharmacology Ligand PfNF54 Parasite growth inhibition assay - - 7.2 pIC50 2
pIC50 7.2 (IC50 6.3x10-8 M) Parasite lactate dehydrogenase (pLDH ) assay [2]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
UCT943 Small molecule or natural product Guide to Malaria Pharmacology Ligand Pf Parasite dual gamete formation assay (DGFA) - - 7.1 pIC50 1
pIC50 7.1 (IC50 8x10-8 M) Reports on the functional viability of male and female mature stage V gametocytes [1]
Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite)
UCT943 Small molecule or natural product Guide to Malaria Pharmacology Ligand Pf Parasite gametocyte viability assay - - 6.9 – 7.2 pIC50 1
pIC50 7.2 (IC50 6.6x10-8 M) Parasite late stage (IV-V) gametocyte assay using luciferase reporter line [1]
Lifecycle stages: Plasmodium sexual blood stage (gametocyte)
pIC50 6.9 (IC50 1.34x10-7 M) Parasite early stage (I-III) gametocyte assay using luciferase reporter line [1]
Lifecycle stages: Plasmodium sexual blood stage (gametocyte)
UCT943 Small molecule or natural product Guide to Malaria Pharmacology Ligand Pf Standard membrane feeding assay (SMFA) - - 7.0 pIC50 1
pIC50 7.0 (IC50 9.6x10-8 M) [1]
Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite)
compound 55 [PMID: 29889526] Small molecule or natural product Guide to Malaria Pharmacology Ligand PfK1 Parasite growth inhibition assay - - 7.0 pIC50 2
pIC50 7.0 (IC50 1.02x10-7 M) Parasite lactate dehydrogenase (pLDH ) assay [2]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
MMV048 Small molecule or natural product Guide to Malaria Pharmacology Ligand Pf Standard membrane feeding assay (SMFA) - - 6.9 pIC50 6
pIC50 6.9 (IC50 1.11x10-7 M) Indirect SMFA [6]
Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite)
KDU691 Small molecule or natural product Guide to Malaria Pharmacology Ligand Pc Parasite liver stage assay - - ~6.7 pIC50 5
pIC50 ~6.7 (IC50 ~1.96x10-7 M) P. cynomolgi infected primary rhesus hepatocyte assay to assess activity against hypnozoites [5]
Lifecycle stages: Plasmodium dormant liver stage (hypnozoite)
MMV048 Small molecule or natural product Guide to Malaria Pharmacology Ligand PfNF54 Parasite gametocyte viability assay - - 6.6 – 6.8 pIC50 6
pIC50 6.8 (IC50 1.4x10-7 M) Parasite late stage (IV-V) gametocyte assay using luciferase reporter line [6]
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 [6]
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 [6]
Lifecycle stages: Plasmodium sexual blood stage (gametocyte)
KDU691 Small molecule or natural product Guide to Malaria Pharmacology Ligand PfNF54 Parasite late stage (III–V) gametocyte assay - - 6.7 pIC50 5
pIC50 6.7 (IC50 2.2x10-7 M) Parasite lactate dehydrogenase (pLDH) assay [5]
Lifecycle stages: Plasmodium sexual blood stage (gametocyte)
MMV024101 Small molecule or natural product Guide to Malaria Pharmacology Ligand PfNF54 Parasite growth inhibition assay - - 6.3 pIC50 2
pIC50 6.3 (IC50 5.43x10-7 M) Parasite lactate dehydrogenase (pLDH ) assay [2]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
MMV048 Small molecule or natural product Guide to Malaria Pharmacology Ligand Pc Parasite liver stage assay - - <5.0 – 7.2 pIC50 6
pIC50 7.2 (IC50 6.1x10-8 M) P. cynomolgi assay to assess inhibition of liver stage development (prophylactic activity) [6]
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) [6]
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) [6]
Lifecycle stages: Plasmodium dormant liver stage (hypnozoite)
Malaria Pharmacology 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 [5]. 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

Show »

1. Brunschwig C, Lawrence N, Taylor D, Abay E, Njoroge M, Basarab GS, Le Manach C, Paquet T, Cabrera DG, Nchinda AT et al.. (2018) UCT943, a Next-Generation Plasmodium falciparum PI4K Inhibitor Preclinical Candidate for the Treatment of Malaria. Antimicrob Agents Chemother, 62 (9). [PMID:29941635]

2. Kandepedu N, Gonzàlez Cabrera D, Eedubilli S, Taylor D, Brunschwig C, Gibhard L, Njoroge M, Lawrence N, Paquet T, Eyermann CJ et al.. (2018) Identification, Characterization, and Optimization of 2,8-Disubstituted-1,5-naphthyridines as Novel Plasmodium falciparum Phosphatidylinositol-4-kinase Inhibitors with in Vivo Efficacy in a Humanized Mouse Model of Malaria. J Med Chem, 61 (13): 5692-5703. [PMID:29889526]

3. Krishnan K, Ziniel P, Li H, Huang X, Hupalo D, Gombakomba N, Guerrero SM, Dotrang T, Lu X, Caridha D et al.. (2020) Torin 2 Derivative, NCATS-SM3710, Has Potent Multistage Antimalarial Activity through Inhibition of P. falciparum Phosphatidylinositol 4-Kinase (Pf PI4KIIIβ). ACS Pharmacol Transl Sci, 3 (5): 948-964. [PMID:33073193]

4. Liang X, Jiang Z, Huang Z, Li F, Chen C, Hu C, Wang W, Hu Z, Liu Q, Wang B et al.. (2020) Discovery of 6'-chloro-N-methyl-5'-(phenylsulfonamido)-[3,3'-bipyridine]-5-carboxamide (CHMFL-PI4K-127) as a novel Plasmodium falciparum PI(4)K inhibitor with potent antimalarial activity against both blood and liver stages of Plasmodium. Eur J Med Chem, 188: 112012. [PMID:31911293]

5. 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]

6. 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

Kinases (Plasmodium spp.): Plasmodium falciparum phosphatidylinositol 4-kinase beta. Last modified on 21/02/2022. Accessed on 27/11/2022. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2972.