ArticlePloS one2016
Biochemical Screening of Five Protein Kinases from Plasmodium falciparum against 14,000 Cell-Active Compounds.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Plasmodial Kinase Inhibitors Targeting Malaria: Recent Developments.Molecules (Basel, Switzerland) · 2020Pooled it
- New thinking for the next generation of antimalarials.EMBO molecular medicine · 2026Review
- Using Unbiased Chemical Proteomics Approaches to Explore the Target Landscape of the Resistance Refractory 7-Azaindole MMV022224 inACS infectious diseases · 2026Article
- Synergistic optimizations of efficacy and membrane permeability of IRAK4 inhibitors: identifying new lead compounds for anti-inflammatory therapeutics.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Computationally guided optimization of the antimalarial activity and physicochemical properties of 2,4-diaminopyrimidines.RSC medicinal chemistry · 2025Article
- Towards next-generation treatment options to combat Plasmodium falciparum malaria.Nature reviews. Microbiology · 2025Review
- An adaptable, fit-for-purpose screening approach with high-throughput capability to determine speed of action and stage specificity of anti-malarial compounds.Antimicrobial agents and chemotherapy · 2024Article
- CACTI: an in silico chemical analysis tool through the integration of chemogenomic data and clustering analysis.Journal of cheminformatics · 2024Article
- Characterization of 2,4-Dianilinopyrimidines Against FiveACS medicinal chemistry letters · 2023Article
- Machine learning-based phenotypic imaging to characterise the targetable biology of Plasmodium falciparum male gametocytes for the development of transmission-blocking antimalarials.PLoS pathogens · 2023Article
- Discovery of potent Plasmodium falciparum protein kinase 6 (PfPK6) inhibitors with a type II inhibitor pharmacophore.European journal of medicinal chemistry · 2023Article
- Preparation, biological evaluation and QSAR analysis of urea substituted 2,4-diamino-pyrimidine anti-malarials.RSC medicinal chemistry · 2022Article
- Screening the Pathogen Box for Inhibition of Plasmodium falciparum Sporozoite Motility Reveals a Critical Role for Kinases in Transmission Stages.Antimicrobial agents and chemotherapy · 2022Article
- Phthalimide analogs for antimalarial drug discovery.RSC medicinal chemistry · 2021Review
- Chemoproteomics for Plasmodium Parasite Drug Target Discovery.Chembiochem : a European journal of chemical biology · 2021Review
- The antimalarial screening landscape-looking beyond the asexual blood stage.Current opinion in chemical biology · 2019Review
- High-throughput screening of the Plasmodium falciparum cGMP-dependent protein kinase identified a thiazole scaffold which kills erythrocytic and sexual stage parasites.Scientific reports · 2019Article
- Integrative Multi-Kinase Approach for the Identification of Potent Antiplasmodial Hits.Frontiers in chemistry · 2019Article
- In silico Screening and Evaluation of Plasmodium falciparum Protein Kinase 5 (PK5) Inhibitors.ChemMedChem · 2018Article
- Screening the Pathogen Box for Molecules Active against Plasmodium Sexual Stages Using a New Nanoluciferase-Based Transgenic Line of P. berghei Identifies Transmission-Blocking Compounds.Antimicrobial agents and chemotherapy · 2018Article
Corrections and comments
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Authors and funding
22 authors at 5 institutions in 5 countries.
Funding
Abstract
In 2010 the identities of thousands of anti-Plasmodium compounds were released publicly to facilitate malaria drug development. Understanding these compounds' mechanisms of action--i.e., the specific molecular targets by which they kill the parasite--would further facilitate the drug development process. Given that kinases are promising anti-malaria targets, we screened ~14,000 cell-active compounds for activity against five different protein kinases. Collections of cell-active compounds from GlaxoSmithKline (the ~13,000-compound Tres Cantos Antimalarial Set, or TCAMS), St. Jude Children's Research Hospital (260 compounds), and the Medicines for Malaria Venture (the 400-compound Malaria Box) were screened in biochemical assays of Plasmodium falciparum calcium-dependent protein kinases 1 and 4 (CDPK1 and CDPK4), mitogen-associated protein kinase 2 (MAPK2/MAP2), protein kinase 6 (PK6), and protein kinase 7 (PK7). Novel potent inhibitors (IC50 < 1 μM) were discovered for three of the kinases: CDPK1, CDPK4, and PK6. The PK6 inhibitors are the most potent yet discovered for this enzyme and deserve further scrutiny. Additionally, kinome-wide competition assays revealed a compound that inhibits CDPK4 with few effects on ~150 human kinases, and several related compounds that inhibit CDPK1 and CDPK4 yet have limited cytotoxicity to human (HepG2) cells. Our data suggest that inhibiting multiple Plasmodium kinase targets without harming human cells is challenging but feasible.
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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.