ArticleMolecular pharmacology2010
A cell-based high-throughput screen validates the plasmodial surface anion channel as an antimalarial target.
Article in Molecular pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 44 citations in OpenAlex.
- The critical role of PSAC channel in malaria parasite survival is driven home by phenotypic screening under relevant nutrient levels.Cell chemical biology · 2025Article
- Utilisation of an in vivo malaria model to provide functional proof for RhopH1/CLAG essentiality and conserved orthology with P. falciparum.Journal of biomedical science · 2025Article
- Guanidinium Chloride-Induced Haemolysis Assay to Measure New Permeation Pathway Functionality in Rodent MalariaBiomolecules · 2024Article
- Critical interdependencies between Plasmodium nutrient flux and drugs.Trends in parasitology · 2023Review
- Conditional permeabilization of the P. falciparum plasma membrane in infected cells links cation influx to reduced membrane integrity.PloS one · 2023Article
- Roles of the RON3 C-terminal fragment in erythrocyte invasion and blood-stage parasite proliferation inFrontiers in cellular and infection microbiology · 2023Article
- Optimized Pyridazinone Nutrient Channel Inhibitors Are Potent and Specific Antimalarial Leads.Molecular pharmacology · 2022Article
- Complex nutrient channel phenotypes despite Mendelian inheritance in a Plasmodium falciparum genetic cross.PLoS pathogens · 2020Article
- Increased CaCellular microbiology · 2018Article
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- TheeLife · 2017Article
- Malaria parasite proteins involved in nutrient channels at the host erythrocyte membrane: advances and questions for future research.International journal of current multidisciplinary studies · 2017Article
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- Identification of inhibitors that dually target the new permeability pathway and dihydroorotate dehydrogenase in the blood stage of Plasmodium falciparum.Scientific reports · 2016Article
- Synergistic Malaria Parasite Killing by Two Types of Plasmodial Surface Anion Channel Inhibitors.PloS one · 2016Article
- A CLAG3 mutation in an amphipathic transmembrane domain alters malaria parasite nutrient channels and confers leupeptin resistance.Infection and immunity · 2015Article
- How do antimalarial drugs reach their intracellular targets?Frontiers in pharmacology · 2015Review
- The conserved clag multigene family of malaria parasites: essential roles in host-pathogen interaction.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2015Review
- A kinetic fluorescence assay reveals unusual features of Ca⁺⁺ uptake in Plasmodium falciparum-infected erythrocytes.Malaria journal · 2014Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The plasmodial surface anion channel (PSAC) is an unusual small-conductance ion channel induced on erythrocytes infected with plasmodia, including parasites responsible for human malaria. Although broadly available inhibitors produce microscopic clearance of parasite cultures at high concentrations and suggest that PSAC is an antimalarial target, they have low affinity for the channel and may interfere with other parasite activities. To address these concerns, we developed a miniaturized assay for PSAC activity and carried out a high-throughput inhibitor screen. Approximately 70,000 compounds from synthetic and natural product libraries were screened, revealing inhibitors from multiple structural classes including two novel and potent heterocyclic scaffolds. Single-channel patch-clamp studies indicated that these compounds act directly on PSAC, further implicating a proposed role in transport of diverse solutes. A statistically significant correlation between channel inhibition and in vitro parasite killing by a family of compounds provided chemical validation of PSAC as a drug target. These new inhibitors should be important research tools and may be starting points for much-needed antimalarial drugs.
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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.