DrugBank screening revealed alitretinoin and bexarotene as liver X receptor modulators. Issue 5 (1st March 2017)

• Record Type: Journal Article
• Authors: Heitel, Pascal; Achenbach, Janosch; Moser, Daniel; Proschak, Ewgenij; Merk, Daniel
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 5(2017)
• Page Start: 1193
• Page End: 1198
• Publication Date: 2017-03-01
• Subjects: Nuclear receptors -- Liver X receptor -- Alitretinoin -- Bexarotene -- SOSA; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.01.066
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: In silico screening of DrugBank database to detect liver X receptor (LXR) agonism of marketed drugs using a self-organizing map and successive LXR-Gal4 hybrid reporter gene assay evaluation in vitro discovered alitretinoin and bexarotene as partial liver X receptor agonists. Dose-response curves demonstrated that plasma concentrations observed in clinical trials are sufficient for LXR activation and thus could account for LXR-mediated side-effects such as hypercholesterolemia and hyperlipidemia. The discovered drugs are the first reported dual LXR/RXR agonists and can serve as lead structures for LXR and dual LXR/RXR modulator development.