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Discovery of new liver X receptor agonists by pharmacophore modeling and shape-based virtual screening.

ABSTRACT: Agonists of liver X receptors (LXR) ? and ? are important regulators of cholesterol metabolism, but agonism of the LXR? subtype appears to cause hepatic lipogenesis, suggesting LXR?-selective activators are attractive new lipid lowering drugs. In this work, pharmacophore modeling and shape-based virtual screening were combined to predict new LXR?-selective ligands. Out of the 10 predicted compounds, three displayed significant LXR activity. Two activated both LXR subtypes. The third compound activated LXR? 1.8-fold over LXR?.

SUBMITTER: Temml V

PROVIDER: S-EPMC3934620 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Discovery of new liver X receptor agonists by pharmacophore modeling and shape-based virtual screening.

Temml Veronika V Voss Constance V CV Dirsch Verena M VM Schuster Daniela D

Journal of chemical information and modeling 20140206 2

Agonists of liver X receptors (LXR) α and β are important regulators of cholesterol metabolism, but agonism of the LXRα subtype appears to cause hepatic lipogenesis, suggesting LXRβ-selective activators are attractive new lipid lowering drugs. In this work, pharmacophore modeling and shape-based virtual screening were combined to predict new LXRβ-selective ligands. Out of the 10 predicted compounds, three displayed significant LXR activity. Two activated both LXR subtypes. The third compound act ...[more]

PMID: 24502802

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