ArticleeLife2015
Identification of NPC1 as the target of U18666A, an inhibitor of lysosomal cholesterol export and Ebola infection.
Article in eLife, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 222 papers.
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Who cites it
222 citing papers in PubMed.
- PDE5A Inhibition Restricts Cancer Metastasis by Disrupting NPC1-Mediated Cholesterol Trafficking through a Noncanonical cGMP-Dependent Pathway.Cancer research · 2026Article
- Pharmacological inhibition of CDK7 and CDK9 suppresses gastrointestinal (colon) cancer progression through modulation of stemness, epithelial-mesenchymal transition, and chemoresistance.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- A Rapamycin Pharmacogenomic Approach for the Childhood Dementia Niemann-Pick C.Journal of inherited metabolic disease · 2026Article
- HKDC1 contributes to aberrant lysosome-mitochondria contact in Niemann-Pick disease type C.bioRxiv : the preprint server for biology · 2026Article
- Morphology-robust quantification of subcellular organization in complex cells.bioRxiv : the preprint server for biology · 2026Article
- Lipid accumulation in tuberculosis granulomas inhibits macrophage-CD4Nature microbiology · 2026Article
- Noncanonical PI(4,5)PScience advances · 2026Article
- A scalable human-zebrafish xenotransplantation model reveals gastrosome-mediated processing of dying neurons by human microglia.Communications biology · 2026Article
- The low-density lipoprotein receptor LDLR mediates cellular entry of nonenveloped hepatitis A virus.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Niemann-Pick type C1 protein regulates epidermal growth factor receptor stability in hepatic cells and facilitates the early steps of Hepatitis B virus infection.Frontiers in cellular and infection microbiology · 2026Article
- Article
- VB-84922 is a small molecule that inhibits ER-to-golgi transport of SREBPs-SCAP complexes.Frontiers in pharmacology · 2026Article
- Repurposing antiviral agents against mucormycosis.PloS one · 2026Article
- NPC1 trafficking via VPS41-dependent LAMP carriers regulates endosomal cholesterol homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Cholesterol Depletion with U18666A and Methyl-β Cyclodextrin Increased Small Molecule Permeability Across Brain Microvascular Endothelial Cells.Annals of biomedical engineering · 2025Article
- mTOR inhibition reprograms cellular lipid homeostasis by inducing alternative lipid uptake and promoting cholesterol transport.Molecular cell · 2025Article
- Impaired Cellular Cholesterol Homeostasis Decreases Tumor-Derived Exosome Load And Modulates Malignant Transformation in Cancer Cells.Cell biochemistry and biophysics · 2025Article
- ATG16L1 WD domain and linker regulates lipid trafficking to maintain plasma membrane integrity to limit influenza virus infection.Autophagy · 2025Article
- Drug-Induced Reversible Lysosomal Changes Tracked in Live Cells by Holo-Tomographic Flow Cytometry.ACS nano · 2025Article
- Tetrandrine regulates NAADP-mediated calcium signaling through a LIMP-2-dependent and sphingosine-mediated mechanism.Nature communications · 2025Article
162 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Niemann-Pick C1 (NPC1) is a lysosomal membrane protein that exports cholesterol derived from receptor-mediated uptake of LDL, and it also mediates cellular entry of Ebola virus. Cholesterol export is inhibited by nanomolar concentrations of U18666A, a cationic sterol. To identify the target of U18666A, we synthesized U-X, a U18666A derivative with a benzophenone that permits ultraviolet-induced crosslinking. When added to CHO cells, U-X crosslinked to NPC1. Crosslinking was blocked by U18666A derivatives that block cholesterol export, but not derivatives lacking blocking activity. Crosslinking was prevented by point mutation in the sterol-sensing domain (SSD) of NPC1, but not by point mutation in the N-terminal domain (NTD). These data suggest that the SSD contains a U18666A-inhibitable site required for cholesterol export distinct from the cholesterol-binding site in the NTD. Inasmuch as inhibition of Ebola requires 100-fold higher concentrations of U18666A, the high affinity U16888A-binding site is likely not required for virus entry.
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