ArticleChemMedChem2012
Identification of drugs inducing phospholipidosis by novel in vitro data.
Article in ChemMedChem, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 65 citations in OpenAlex.
- Development and characterization of triazole-based WDR5 inhibitors for the treatment of glioblastoma.JCI insight · 2026Article
- Experimentally derived biomimetic chromatographic descriptors for drug-induced phospholipidosis liability prediction.ADMET & DMPK · 2026Article
- Cepharanthine inhibits enterovirus entry by endolysosomal deacidification and exhibits protective activityAntimicrobial agents and chemotherapy · 2025Article
- Predicting Liver-Related In Vitro Endpoints with Machine Learning to Support Early Detection of Drug-Induced Liver Injury.Chemical research in toxicology · 2025Article
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- Identification of kinase modulators as host-directed therapeutics against intracellular methicillin-resistantFrontiers in cellular and infection microbiology · 2024Article
- Zebra Body Not Caused by Fabry Disease.Internal medicine (Tokyo, Japan) · 2023Article
- Raloxifene induced keratopathy: A case report.American journal of ophthalmology case reports · 2022Article
- Understanding COVID-19 Pathogenesis: A Drug-Repurposing Effort to Disrupt Nsp-1 Binding to Export Machinery Receptor Complex.Pathogens (Basel, Switzerland) · 2021Article
- Detailed Phenotype of GLA Variants Identified by the Nationwide Neurological Screening of Stroke Patients in the Czech Republic.Journal of clinical medicine · 2021Article
- Drug-induced phospholipidosis confounds drug repurposing for SARS-CoV-2.Science (New York, N.Y.) · 2021Article
- Phospholipidosis is a shared mechanism underlying thebioRxiv : the preprint server for biology · 2021Article
- Zebra Body Formation Due to Drug-Induced Phospholipidosis Observed on Electron Micrographs.Circulation reports · 2021Article
- Chemoinformatic Analysis of Psychotropic and Antihistaminic Drugs in the Light of Experimental Anti-SARS-CoV-2 Activities.Advances and applications in bioinformatics and chemistry : AABC · 2021Article
- Prevention of COVID-19 by drug repurposing: rationale from drugs prescribed for mental disorders.Drug discovery today · 2020Article
- Characterization of the small molecule ARC39, a direct and specific inhibitor of acid sphingomyelinase in vitro.Journal of lipid research · 2020Article
- Psychotropic Drugs Show Anticancer Activity by Disrupting Mitochondrial and Lysosomal Function.Frontiers in oncology · 2020Article
- Wide field retinal imaging and the detection of drug associated retinal toxicity.International journal of retina and vitreous · 2019Review
- Computational Assessment of the Pharmacological Profiles of Degradation Products of Chitosan.Frontiers in bioengineering and biotechnology · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Drug-induced phospholipidosis (PLD) is a lysosomal storage disorder characterized by the accumulation of phospholipids within the lysosome. This adverse drug effect can occur in various tissues and is suspected to impact cellular viability. Therefore, it is important to test chemical compounds for their potential to induce PLD during the drug design process. PLD has been reported to be a side effect of many commonly used drugs, especially those with cationic amphiphilic properties. To predict drug-induced PLD in silico, we established a high-throughput cell-culture-based method to quantitatively determine the induction of PLD by chemical compounds. Using this assay, we tested 297 drug-like compounds at two different concentrations (2.5 μM and 5.0 μM). We were able to identify 28 previously unknown PLD-inducing agents. Furthermore, our experimental results enabled the development of a binary classification model to predict PLD-inducing agents based on their molecular properties. This random forest prediction system yields a bootstrapped validated accuracy of 86 %. PLD-inducing agents overlap with those that target similar biological processes; a high degree of concordance with PLD-inducing agents was identified for cationic amphiphilic compounds, small molecules that inhibit acid sphingomyelinase, compounds that cross the blood-brain barrier, and compounds that violate Lipinski's rule of five. Furthermore, we were able to show that PLD-inducing compounds applied in combination additively induce PLD.
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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.