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American Chemical Society, Journal of Chemical Information and Modeling, 5(52), p. 1391-1400, 2012

DOI: 10.1021/ci300096c

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Identification of Novel Liver X Receptor Activators by Structure-Based Modeling

Journal article published in 2012 by Susanne von Grafenstein, Judit Mihaly-Bison, Gerhard Wolber ORCID, Valery N. Bochkov, Klaus R. Liedl, Daniela Schuster ORCID
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Liver X receptors (LXRs) are members of the nuclear receptor family. Activators of LXRs are of high pharmacological interest as LXRs regulate cholesterol, fatty acid, and carbohydrate metabolism as well as inflammatory processes. On the basis of different X-ray crystal structures, we established a virtual screening workflow for the identification of novel LXR modulators. A two-step screening concept to identify active compounds included 3D-pharmacophore filters and rescoring by shape alignment. Eighteen virtual hits were tested in vitro applying a reporter gene assay, where concentration-dependent activity was proven for four novel lead structures. The most active compound 10, a 1,4-naphthochinone, has an estimated EC₅₀ of around 5 μM.