ArticleOncotarget2017
Identifying the structure-activity relationship of leelamine necessary for inhibiting intracellular cholesterol transport.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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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
15 citing papers in PubMed, 28 citations in OpenAlex.
- The Role of Plant-Derived Natural Products as a Regulator of the Tyrosine Kinase Pathway in the Management of Lung Cancer.Current issues in molecular biology · 2025Review
- Iterative One-Carbon Homologation of Unmodified Carboxylic Acids.Journal of the American Chemical Society · 2024Article
- In Vitro Cytotoxic Effects of Ferruginol Analogues in Sk-MEL28 Human Melanoma Cells.International journal of molecular sciences · 2023Article
- Potential Application of Leelamine as a Novel Regulator of Chemokine-Induced Epithelial-to-Mesenchymal Transition in Breast Cancer Cells.International journal of molecular sciences · 2022Article
- Linking Late Endosomal Cholesterol with Cancer Progression and Anticancer Drug Resistance.International journal of molecular sciences · 2022Review
- Targeting WEE1/AKT Restores p53-Dependent Natural Killer-Cell Activation to Induce Immune Checkpoint Blockade Responses in "Cold" Melanoma.Cancer immunology research · 2022Article
- Targeting Protein Translation in Melanoma by Inhibiting EEF-2 Kinase Regulates Cholesterol Metabolism though SREBP2 to Inhibit Tumour Development.International journal of molecular sciences · 2022Article
- Leelamine Modulates STAT5 Pathway Causing Both Autophagy and Apoptosis in Chronic Myelogenous Leukemia Cells.Biology · 2022Article
- Lipid metabolic Reprogramming: Role in Melanoma Progression and Therapeutic Perspectives.Cancers · 2020Review
- Article
- Development of a Novel Multi-Isoform ALDH Inhibitor Effective as an Antimelanoma Agent.Molecular cancer therapeutics · 2020Article
- Salubrinal in Combination With 4E1RCat Synergistically Impairs Melanoma Development by Disrupting the Protein Synthetic Machinery.Frontiers in oncology · 2020Article
- A Brief Overview of the Antitumoral Actions of Leelamine.Biomedicines · 2019Review
- Nanoliposomal delivery of cytosolic phospholipase ANanomedicine : nanotechnology, biology, and medicine · 2018Article
- Moving Synergistically Acting Drug Combinations to the Clinic by Comparing Sequential versus Simultaneous Drug Administrations.Molecular pharmacology · 2018Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Leelamine is an anticancer chemotherapeutic agent inhibiting intracellular cholesterol transport. Cell death mediated by leelamine occurs due to the lysosomotropic property of the compound, its accumulation in the lysosome, and inhibition of cholesterol transport leading to lack of availability for key processes required for functioning of cancer cells. The present study dissects the structure-activity-relationship of leelamine using synthesized derivatives of leelamine and abietic acid, a structurally similar compound, to identify the moiety responsible for anti-cancer activity. Similar to leelamine, all active derivatives had an amino group or a similar moiety that confers a lysosomotropic property to the compound enabling its accumulation in the lysosome. Active derivatives inhibited intracellular cholesterol transport and hindered xenografted melanoma tumor development without obvious systemic toxicity. In silico studies suggested that active derivatives accumulating in lysosomes bound to NPC1, a protein responsible for cholesterol export from the lysosome, to inhibit its activity that then caused accumulation, and lack of cholesterol availability for other key cellular activities. Thus, active derivatives of leelamine or abietic acid maintained lysosomotropic properties, bound to NPC1, and disrupted cellular cholesterol transport as well as availability to retard tumor development.
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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.