ArticleNature chemical biology2025
Orpinolide disrupts a leukemic dependency on cholesterol transport by inhibiting OSBP.
Article in Nature chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 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
10 citing papers in PubMed.
- Design and synthesis of oxathiapiprolin derivatives containing acetal fragments as potent fungicide candidates.Pest management science · 2026Article
- Cell painting and thermal proteome profiling for inference of drug targets and mechanism of action.Molecular systems biology · 2026Article
- Stress-induced proteome remodeling at the Golgi-endosome interface.Journal of cell science · 2026Article
- Role of Oxysterol-Binding Protein Family in Cholesterol Metabolism and Cancer Progression: A Review.Medical science monitor : international medical journal of experimental and clinical research · 2026Review
- Emerging roles of lipid transfer protein dimerization.Journal of cell science · 2025Review
- Phylogenomics and metabolic engineering reveal a conserved gene cluster in Solanaceae plants for withanolide biosynthesis.Nature communications · 2025Article
- Emerging Approaches for Studying Lipid Dynamics, Metabolism, and Interactions in Cells.Annual review of biochemistry · 2025Review
- Subfunctionalization and epigenetic regulation of a biosynthetic gene cluster inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- All roads lead to OSBP.Nature chemical biology · 2025Article
- Getting to Grips with the Oxysterol-Binding Protein Family - a Forty Year Perspective.Contact (Thousand Oaks (Ventura County, Calif.))Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors.
Funding
Abstract
Metabolic alterations in cancer precipitate in associated dependencies that can be therapeutically exploited. To meet this goal, natural product-inspired small molecules can provide a resource of invaluable chemotypes. Here, we identify orpinolide, a synthetic withanolide analog with pronounced antileukemic properties, via orthogonal chemical screening. Through multiomics profiling and genome-scale CRISPR-Cas9 screens, we identify that orpinolide disrupts Golgi homeostasis via a mechanism that requires active phosphatidylinositol 4-phosphate signaling at the endoplasmic reticulum-Golgi membrane interface. Thermal proteome profiling and genetic validation studies reveal the oxysterol-binding protein OSBP as the direct and phenotypically relevant target of orpinolide. Collectively, these data reaffirm sterol transport as a therapeutically actionable dependency in leukemia and motivate ensuing translational investigation via the probe-like compound orpinolide.
Indexed as
Identifiers
What OpenQuestion holds
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.