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Plasmodium falciparum plasmepsin X

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Target id: 3071

Nomenclature: Plasmodium falciparum plasmepsin X

Abbreviated Name: PfPMX

Family: Peptidases and proteinases (Plasmodium spp.)

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Plasmodium falciparum 3D7 - 573 PMX plasmepsin X
Previous and Unofficial Names Click here for help
PF08_0108
Database Links Click here for help
Alphafold
ChEMBL Target
PlasmoDB
UniProtKB
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
WM382 Small molecule or natural product Ligand has a PDB structure Guide to Malaria Pharmacology Ligand Pf Inhibition 10.5 pKi 4
pKi 10.5 (Ki 3.5x10-11 M) [4]
Description: Peptide cleavage assay using recombinant PMX
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
WM382 Small molecule or natural product Ligand has a PDB structure Guide to Malaria Pharmacology Ligand Pk Parasite growth inhibition assay - - 9.7 pEC50 4
pEC50 9.7 (EC50 1.8x10-10 M) SYBR Green assay [4]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Compound 14a [WO2021155612A1] Small molecule or natural product Guide to Malaria Pharmacology Ligand Pf Parasite growth inhibition assay - - 9.7 pEC50 3
pEC50 9.7 (EC50 2x10-10 M) Parasite lactate dehydrogenase (pLDH ) assay following 72 hours in culture [3]
WM382 Small molecule or natural product Ligand has a PDB structure Guide to Malaria Pharmacology Ligand PfDd2 Parasite growth inhibition assay - - 9.6 pEC50 4
pEC50 9.6 (EC50 2.6x10-10 M) [4]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
WM382 Small molecule or natural product Ligand has a PDB structure Guide to Malaria Pharmacology Ligand Pf3D7 Parasite growth inhibition assay - - 9.2 pEC50 4
pEC50 9.2 (EC50 6x10-10 M) Results are for R-WM382 [4]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
WM382 Small molecule or natural product Ligand has a PDB structure Guide to Malaria Pharmacology Ligand PfK1 Parasite growth inhibition assay - - 9.2 pEC50 4
pEC50 9.2 (EC50 6.5x10-10 M) [4]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
compound 49c [PMID: 29074775] Small molecule or natural product Guide to Malaria Pharmacology Ligand PfNF54 Parasite growth inhibition assay - - 6.3 – 9.2 pIC50 1
pIC50 9.2 (IC50 6x10-10 M) [3H]-hypoxanthine incorporation following 72 h incubation [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
pIC50 <6.3 (IC50 >5x10-7 M) [3H]-hypoxanthine incorporation following 24 h incubation [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
WM382 Small molecule or natural product Ligand has a PDB structure Guide to Malaria Pharmacology Ligand Pf Standard membrane feeding assay (SMFA) - - - - 4
Oocyst count: potent inhibition of oocyst development [4]
Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite)
Malaria Pharmacology Comments
The P. falciparum genome encodes 10 aspartic proteases, classed together as the plasmepsin family, which are involved in diverse cellular processes [2]. P. falciparum plasmepsin X (PfPMX) has emerged as a promising target for antimalarial drug development with studies demonstrating an essential role in merozoite invasion and egress of erythrocytes [5-6].

References

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1. Ciana CL, Siegrist R, Aissaoui H, Marx L, Racine S, Meyer S, Binkert C, de Kanter R, Fischli C, Wittlin S et al.. (2013) Novel in vivo active anti-malarials based on a hydroxy-ethyl-amine scaffold. Bioorg Med Chem Lett, 23 (3): 658-62. [PMID:23260352]

2. Coombs GH, Goldberg DE, Klemba M, Berry C, Kay J, Mottram JC. (2001) Aspartic proteases of Plasmodium falciparum and other parasitic protozoa as drug targets. Trends Parasitol, 17 (11): 532-7. [PMID:11872398]

3. De Lera Ruiz M., Favuzza P., Guo Z., Hu B. et al.. (2021) Antimalarial agents. Patent number: WO2021155612A1. Assignee: Merck Sharp & Dohme Corp., The Walter and Eliza Hall Insitute of Medical Research, MSD R&D. Priority date: 09/02/2020. Publication date: 12/08/2021.

4. Favuzza P, de Lera Ruiz M, Thompson JK, Triglia T, Ngo A, Steel RWJ, Vavrek M, Christensen J, Healer J, Boyce C et al.. (2020) Dual Plasmepsin-Targeting Antimalarial Agents Disrupt Multiple Stages of the Malaria Parasite Life Cycle. Cell Host Microbe, 27 (4): 642-658.e12. [PMID:32109369]

5. Nasamu AS, Glushakova S, Russo I, Vaupel B, Oksman A, Kim AS, Fremont DH, Tolia N, Beck JR, Meyers MJ et al.. (2017) Plasmepsins IX and X are essential and druggable mediators of malaria parasite egress and invasion. Science, 358 (6362): 518-522. [PMID:29074774]

6. Pino P, Caldelari R, Mukherjee B, Vahokoski J, Klages N, Maco B, Collins CR, Blackman MJ, Kursula I, Heussler V et al.. (2017) A multistage antimalarial targets the plasmepsins IX and X essential for invasion and egress. Science, 358 (6362): 522-528. [PMID:29074775]

How to cite this page

Peptidases and proteinases (Plasmodium spp.): Plasmodium falciparum plasmepsin X. Last modified on 31/03/2022. Accessed on 28/06/2022. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=3071.