ArticlePloS one2018
Apilimod, a candidate anticancer therapeutic, arrests not only PtdIns(3,5)P2 but also PtdIns5P synthesis by PIKfyve and induces bafilomycin A1-reversible aberrant endomembrane dilation.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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
20 citing papers in PubMed, 37 citations in OpenAlex.
- Quantitative comparison of PI(3,5)PMolecular biology of the cell · 2026Article
- PIKfyve preserves endolysosomal function in photoreceptors and RPE cells to maintain retinal integrity.Cell death & disease · 2026Article
- Approaches to visualize, quantify, and manipulate phosphoinositides in cells.Histochemistry and cell biology · 2026Review
- Phosphoinositide kinase PIKfyve inhibitor apilimod blocks hepatitis E virus infection.eGastroenterology · 2026Article
- Quantitative comparison of PI(3,5)PbioRxiv : the preprint server for biology · 2025Article
- Concurrent Inhibition of the RAS-MAPK Pathway and PIKfyve Is a Therapeutic Strategy for Pancreatic Cancer.Cancer research · 2025Article
- Review
- Discovery of a First-in-Class Degrader for the Lipid Kinase PIKfyve.Journal of medicinal chemistry · 2023Article
- Small molecules targeting endocytic uptake and recycling pathways.Frontiers in cell and developmental biology · 2023Review
- Measles and Nipah virus assembly: Specific lipid binding drives matrix polymerization.Science advances · 2022Article
- Evaluation of Phenol-Substituted Diphyllin Derivatives as Selective Antagonists for Ebola Virus Entry.ACS infectious diseases · 2022Article
- Computational determination of toxicity risks associated with a selection of approved drugs having demonstrated activity against COVID-19.BMC pharmacology & toxicology · 2021Article
- Live imaging of intra-lysosome pH in cell lines and primary neuronal culture using a novel genetically encoded biosensor.Autophagy · 2021Article
- Experimental Pharmacotherapy for COVID-19: The Latest Advances.Journal of experimental pharmacology · 2021Review
- From Pinocytosis to Methuosis-Fluid Consumption as a Risk Factor for Cell Death.Frontiers in cell and developmental biology · 2021Review
- Phosphatidylinositol 4,5-bisphosphate is regenerated by speeding of the PI 4-kinase pathway during long PLC activation.The Journal of general physiology · 2020Article
- Targeting Crucial Host Factors of SARS-CoV-2.ACS infectious diseases · 2020Review
- Article
- Regulation of V-ATPase Activity and Organelle pH by Phosphatidylinositol Phosphate Lipids.Frontiers in cell and developmental biology · 2020Review
- Severe Consequences of SAC3/FIG4 Phosphatase Deficiency to Phosphoinositides in Patients with Charcot-Marie-Tooth Disease Type-4J.Molecular neurobiology · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
PIKfyve, an evolutionarily conserved kinase synthesizing PtdIns5P and PtdIns(3,5)P2, is crucial for mammalian cell proliferation and viability. Accordingly, PIKfyve inhibitors are now in clinical trials as anti-cancer drugs. Among those, apilimod is the most promising, yet its potency to inhibit PIKfyve and affect endomembrane homeostasis is only partially characterized. We demonstrate here for the first time that apilimod powerfully inhibited in vitro synthesis of PtdIns5P along with that of PtdIns(3,5)P2. HPLC-based resolution of intracellular phosphoinositides (PIs) revealed that apilimod triggered a marked reduction of both lipids in the context of intact cells. Notably, there was also a profound rise in PtdIns3P resulting from arrested PtdIns3P consumption for PtdIns(3,5)P2 synthesis. As typical for PIKfyve inhibition and the concomitant PtdIns(3,5)P2 reduction, apilimod induced the appearance of dilated endomembrane structures in the form of large translucent cytoplasmic vacuoles. Remarkably, bafilomycin A1 (BafA1) fully reversed the aberrant cell phenotype back to normal and completely precluded the appearance of cytoplasmic vacuoles when added prior to apilimod. Inspection of the PI profiles ruled out restoration of the reduced PtdIns(3,5)P2 pool as a molecular mechanism underlying BafA1 rescue. Rather, we found that BafA1 markedly attenuated the PtdIns3P elevation under PIKfyve inhibition. This was accompanied by profoundly decreased endosomal recruitment of fusogenic EEA1. Together, our data demonstrate that apilimod inhibits not only PtdIns(3,5)P2 but also PtdIns5P synthesis and that the cytoplasmic vacuolization triggered by the inhibitor is precluded or reversed by BafA1 through a mechanism associated, in part, with reduction in both PtdIns3P levels and EEA1 membrane recruitment.
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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 Socratic graph.