ArticleNature chemical biology2025
Inhibition of OSBP blocks retrograde trafficking by inducing partial Golgi degradation.
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 13 papers.
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Who cites it
13 citing papers in PubMed.
- Golgi dysfunction in Alzheimer disease: from human multiomic signatures to therapeutic targets.Experimental & molecular medicine · 2026Review
- Design and synthesis of oxathiapiprolin derivatives containing acetal fragments as potent fungicide candidates.Pest management science · 2026Article
- Photosensitizer proximity labeling captures the lipid and protein interactomes.Nature chemical biology · 2026Article
- Article
- Poliovirus 3Dpol polymerase region is essential for cleavage of poliovirus 3AB in vivo.PLoS pathogens · 2026Article
- Stress-induced proteome remodeling at the Golgi-endosome interface.Journal of cell science · 2026Article
- Potent Inducers of Paraptosis through Electronic Tuning of Hemicyanine Electrophiles.Journal of the American Chemical Society · 2025Article
- Article
- Orpinolide disrupts a leukemic dependency on cholesterol transport by inhibiting OSBP.Nature chemical biology · 2025Article
- Identification of a Privileged Scaffold for Inhibition of Sterol Transport Proteins through the Synthesis and Ring Distortion of Diverse, Pseudo-Natural Products.ACS central science · 2025Article
- Dysregulation of PI4P in the trans Golgi regions activates the mammalian Golgi stress response.The Journal of biological chemistry · 2025Article
- Dysregulation of PI4P in the trans Golgi regions activates the mammalian Golgi stress response.The Journal of biological chemistry · 2025Article
- Endogenous and fluorescent sterols reveal the molecular basis for ligand selectivity of human sterol transporters.bioRxiv : the preprint server for biology · 2024Article
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Authors and funding
14 authors.
Funding
Abstract
Sterol-binding proteins are important regulators of lipid homeostasis and membrane integrity; however, the discovery of selective modulators can be challenging due to structural similarities in the sterol-binding domains. We report the discovery of potent and selective inhibitors of oxysterol-binding protein (OSBP), which we term oxybipins. Sterol-containing chemical chimeras aimed at identifying new sterol-binding proteins by targeted degradation, led to a significant reduction in levels of Golgi-associated proteins. The degradation occurred in lysosomes, concomitant with changes in protein glycosylation, indicating that the degradation of Golgi proteins was a downstream effect. By establishing a sterol transport protein biophysical assay panel, we discovered that the oxybipins potently inhibited OSBP, resulting in blockage of retrograde trafficking and attenuating Shiga toxin toxicity. As the oxybipins do not target other sterol transporters and only stabilized OSBP in intact cells, we advocate their use as tools to study OSBP function and therapeutic relevance.
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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.