ReviewLipids2009
Cholesterol synthesis inhibitor U18666A and the role of sterol metabolism and trafficking in numerous pathophysiological processes.
Review in Lipids, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers, 1 of them a synthesis that pooled it.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
129 citing papers in PubMed, 1 synthesis or guideline pooled it, 207 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Efficacy of N-acetylcysteine in phenotypic suppression of mouse models of Niemann-Pick disease, type C1.Human molecular genetics · 2013Trial
- Identification and characterization of anti-chikungunya virus compounds using a biosafe toolkit.Virologica Sinica · 2026Article
- A cell-based Sonic Hedgehog signaling transduction system to identify additive and synergistic chemical interactions.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Cholesterol Depletion with U18666A and Methyl-β Cyclodextrin Increased Small Molecule Permeability Across Brain Microvascular Endothelial Cells.Annals of biomedical engineering · 2025Article
- NPC1 controls TGFBR1 stability in a cholesterol transport-independent manner and promotes hepatocellular carcinoma progression.Nature communications · 2025Article
- Instationary metabolic flux analysis reveals that NPC1 inhibition increases glycolysis and decreases mitochondrial metabolism in brain microvascular endothelial cells.Neurobiology of disease · 2025Article
- The inactivation of the Niemann Pick C1 cholesterol transporter restricts SARS-CoV-2 entry into host cells by decreasing ACE2 abundance at the plasma membrane.Cell & bioscience · 2024Article
- Numb-associated kinases regulate sandfly-borne Toscana virus entry.Emerging microbes & infections · 2024Article
- Why make it if you can take it: review on extracellular cholesterol uptake and its importance in breast and ovarian cancers.Journal of experimental & clinical cancer research : CR · 2024Review
- An Optimized Human Erythroblast Differentiation System Reveals Cholesterol-Dependency of Robust Production of Cultured Red Blood Cells Ex Vivo.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Potential Use of the Cholesterol Transfer Inhibitor U18666A as a Potent Research Tool for the Study of Cholesterol Mechanisms in Neurodegenerative Disorders.Molecular neurobiology · 2024Review
- Entry inhibitors as arenavirus antivirals.Frontiers in microbiology · 2024Review
- Article
- Cyclodextrin-Mediated Cholesterol Depletion Induces Adiponectin Secretion in 3T3-L1 Adipocytes.International journal of molecular sciences · 2023Article
- Statins suppress cell-to-cell propagation of α-synuclein by lowering cholesterol.Cell death & disease · 2023Article
- Early Endosomes Act as Local Exocytosis Hubs to Repair Endothelial Membrane Damage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Identification and quantification of ionising radiation-induced oxysterol formation in membranes of lens fibre cells.Advances in redox research · 2023Article
- Cholesterol and its reciprocal association with prion infection.Cell and tissue research · 2023Review
- Virtual Screening of Novel 24-Dehydroxysterol Reductase (Molecules (Basel, Switzerland) · 2023Article
69 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
The multiple actions of U18666A have enabled major discoveries in lipid research and contributed to understanding the pathophysiology of multiple diseases. This review describes these advances and the utility of U18666A as a tool in lipid research. Harry Rudney's recognition that U18666A inhibited oxidosqualene cyclase led him to discover a pathway for formation of polar sterols that he proved to be important regulators of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase. Laura Liscum's recognition that U18666A inhibited the egress of cholesterol from late endosomes and lysosomes led to greatly improved perspective on the major pathways of intracellular cholesterol trafficking. The inhibition of cholesterol trafficking by U18666A mimicked the loss of functional Niemann-Pick type C protein responsible for NPC disease and thus provided a model for this disorder. U18666A subsequently became a tool for assessing the importance of molecular trafficking through the lysosomal pathway in other conditions such as atherosclerosis, Alzheimer's disease, and prion infections. U18666A also provided animal models for two important disorders: petite mal (absence) epilepsy and cataracts. This was the first chronic model of absence epilepsy. U18666A is also being used to address the role of oxidative stress in apoptosis. How can one molecule have so many effects? Perhaps because of its structure as an amphipathic cationic amine it can interact and inhibit diverse proteins. Restricting the availability of cholesterol for membrane formation through inhibition of cholesterol synthesis and intracellular trafficking could also be a mechanism for broadly affecting many processes. Another possibility is that through intercalation into membrane U18666A can alter membrane order and therefore the function of resident proteins. The similarity of the effects of natural and enantiomeric U18666A on cells and the capacity of intercalated U18666A to increase membrane order are arguments in favor of this possibility.
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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.