2. Academic Validation
  3. DrugBank screening revealed alitretinoin and bexarotene as liver X receptor modulators

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

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: merk@pharmchem.uni-frankfurt.de.
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.

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