ArticleAntimicrobial agents and chemotherapy2014
Biochemical and antiparasitic properties of inhibitors of the Plasmodium falciparum calcium-dependent protein kinase PfCDPK1.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Plasmodial Kinase Inhibitors Targeting Malaria: Recent Developments.Molecules (Basel, Switzerland) · 2020Pooled it
- Biological evaluation of novel side chain containing CQTrICh-analogs as antimalarials and their development asHeliyon · 2024Article
- Chemo-proteomics in antimalarial target identification and engagement.Medicinal research reviews · 2023Review
- Adapt or Die: Targeting Unique Transmission-Stage Biology for Malaria Elimination.Frontiers in cellular and infection microbiology · 2022Review
- Review
- CDPKs: The critical decoders of calcium signal at various stages of malaria parasite development.Computational and structural biotechnology journal · 2021Review
- cAMP-Dependent Signaling Pathways as Potential Targets for Inhibition ofFrontiers in microbiology · 2021Review
- An Update on Development of Small-Molecule Plasmodial Kinase Inhibitors.Molecules (Basel, Switzerland) · 2020Review
- Overlapping and distinct roles of CDPK family members in the pre-erythrocytic stages of the rodent malaria parasite, Plasmodium berghei.PLoS pathogens · 2020Article
- Whole-Cell Phenotypic Screening of Medicines for Malaria Venture Pathogen Box Identifies Specific Inhibitors ofAntimicrobial agents and chemotherapy · 2020Article
- Targeting the Malaria Parasite cGMP-Dependent Protein Kinase to Develop New Drugs.Frontiers in microbiology · 2020Review
- Targeting malaria parasite invasion of red blood cells as an antimalarial strategy.FEMS microbiology reviews · 2019Review
- Plasmodial Kinase Inhibitors: License to Cure?Journal of medicinal chemistry · 2018Article
- The calcium-dependent protein kinase 1 from Toxoplasma gondii as target for structure-based drug design.Parasitology · 2018Review
- Imidazopyridazine Inhibitors of Plasmodium falciparum Calcium-Dependent Protein Kinase 1 Also Target Cyclic GMP-Dependent Protein Kinase and Heat Shock Protein 90 To Kill the Parasite at Different Stages of Intracellular Development.Antimicrobial agents and chemotherapy · 2015Article
- Development of a Reagentless Biosensor for Inorganic Phosphate, Applicable over a Wide Concentration Range.Biochemistry · 2015Article
- Designing selective inhibitors for calcium-dependent protein kinases in apicomplexans.Trends in pharmacological sciences · 2015Review
- Calcium-dependent Protein Kinases in Malaria Parasite Development and Infection.Cell transplantationArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 1 institution in 1 country.
Funding
Abstract
PfCDPK1 is a Plasmodium falciparum calcium-dependent protein kinase, which has been identified as a potential target for novel antimalarial chemotherapeutics. In order to further investigate the role of PfCDPK1, we established a high-throughput in vitro biochemical assay and used it to screen a library of over 35,000 small molecules. Five chemical series of inhibitors were initially identified from the screen, from which series 1 and 2 were selected for chemical optimization. Indicative of their mechanism of action, enzyme inhibition by these compounds was found to be sensitive to both the ATP concentration and substitution of the amino acid residue present at the "gatekeeper" position at the ATP-binding site of the enzyme. Medicinal chemistry efforts led to a series of PfCDPK1 inhibitors with 50% inhibitory concentrations (IC50s) below 10 nM against PfCDPK1 in a biochemical assay and 50% effective concentrations (EC50s) less than 100 nM for inhibition of parasite growth in vitro. Potent inhibition was combined with acceptable absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties and equipotent inhibition of Plasmodium vivax CDPK1. However, we were unable to correlate biochemical inhibition with parasite growth inhibition for this series overall. Inhibition of Plasmodium berghei CDPK1 correlated well with PfCDPK1 inhibition, enabling progression of a set of compounds to in vivo evaluation in the P. berghei rodent model for malaria. These chemical series have potential for further development as inhibitors of CDPK1.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.