Targeting the isoprenoid pathway in choleste biosynthesis: An approach to identify isoprenoid biosynthesis inhibitors.

ABSTRACT: The development of novel cholesterol biosynthesis inhibitors is a task of major concern due to the diverse roles of cholesterol and its precursors in physiological processes. Therefore, appropriate screening assays are required, which can be used to identify and quantify specific inhibitors targeting the desired enzyme. Here, we developed a whole-cell screening assay based on a HL60 cell line, which can be used to characterize inhibitors interacting with enzymes of the isoprenoid part of cholesterol biosynthesis. Due to the change of the isoprenoid pattern under enzyme inhibition, an identification of the targeted enzyme is possible. With the described assay, we can distinguish between free and pyrophosphorylated isoprenoids after enzymatic cleavage in cellular and extracellular matrices.

SUBMITTER: Liebl M 

PROVIDER: S-EPMC11823600 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature