DrugBank screening revealed alitretinoin and bexarotene as liver X receptor modulators

  • Bioorg Med Chem Lett. 2017 Mar 1;27(5):1193-1198. doi: 10.1016/j.bmcl.2017.01.066.
Pascal Heitel  1 ,  Janosch Achenbach  1 ,  Daniel Moser  1 ,  Ewgenij Proschak  1 ,  Daniel Merk  2
Affiliations
  • 1. Institute of Pharmaceutical Chemistry, Goethe-University Frankfurt, Max-von-Laue-Strasse 9, 60438 Frankfurt am Main, Germany.
  • 2. Institute of Pharmaceutical Chemistry, Goethe-University Frankfurt, Max-von-Laue-Strasse 9, 60438 Frankfurt am Main, Germany. Electronic address: [email protected].
PMID: 28169169 DOI: 10.1016/j.bmcl.2017.01.066
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.

Keywords
Alitretinoin; Bexarotene; Liver X receptor; Nuclear receptors; SOSA.