Discovery of selective ACAT2 antagonist via a combination strategy based on deep docking, pharmacophore modelling, and molecular dynamics simulation.

ABSTRACT: Acyl-CoA: cholesterol acyltransferase (ACAT), a pivotal enzyme in the absorption and metabolism of cholesterol, is primarily responsible for intracellular esterification. ACAT inhibition is expected to diminish plasma lipid levels by impeding intestinal cholesterol absorption, thereby preventing the progression of atherosclerotic lesions. A previous study shows that selective inhibition of ACAT2 significantly mitigated hypercholesterolaemia and atherosclerosis in mouse models. Therefore, the need for ACAT2 selective inhibitors becomes particularly urgent. In this study, we established a multilayer virtual screening workflow and subjected biologically evaluated representative compounds to enzyme inhibitory assays. The experimental results indicated that the two compounds, STL565001 (inhibit

SUBMITTER: Liu Y 

PROVIDER: S-EPMC11423527 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature