ArticleACS central science2025
Identification of a Privileged Scaffold for Inhibition of Sterol Transport Proteins through the Synthesis and Ring Distortion of Diverse, Pseudo-Natural Products.
Article in ACS central science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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The trial behind it
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Who cites it
5 citing papers in PubMed.
- Article
- Design, Synthesis, and Biological Evaluation of Pseudo-Natural Products Inspired by Aryloctahydroindole Alkaloids.ChemMedChem · 2026Article
- Pseudonatural Products for Chemical Biology and Drug Discovery.Journal of medicinal chemistry · 2025Review
- An Indole Dearomatization Strategy for the Synthesis of Pseudo-Natural Products.Chembiochem : a European journal of chemical biology · 2025Article
- Unifying principles for the design and evaluation of natural product-inspired compound collections.Chemical science · 2025Review
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sterol transport proteins mediate intracellular sterol transport, organelle contact sites, and lipid metabolism. Despite their importance, the similarities in their sterol-binding domains have made the identification of selective modulators difficult. Herein we report a combination of different compound library synthesis strategies to prepare a cholic acid-inspired compound collection for the identification of potent and selective inhibitors of sterol transport proteins. The fusion of a primary sterol scaffold with a range of different fragments found in natural products followed by various ring distortions allowed the synthesis of diverse sterol-inspired compounds. This led to the identification of a complex and three-dimensional spirooxepinoindole as a privileged scaffold for sterol transport proteins. With careful optimization of the scaffold, the selectivity could be directed toward a single transporter, as showcased by the development of a potent and selective Aster-A inhibitor. We suggest that the combination of different design strategies is generally applicable for the identification of potent and selective bioactive compounds with drug-like properties.
Identifiers
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Registered trials
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