Identification of a Privileged Scaffold for Inhibition of Sterol Transport Proteins through the Synthesis and Ring Distortion of Diverse, Pseudo-Natural Products.

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 tran

SUBMITTER: Bro FS 

PROVIDER: S-EPMC11758220 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature