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. Epub 2017 Jan 25.


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.

MeSH terms

  • Alitretinoin
  • Animals
  • Bexarotene
  • Drug Evaluation, Preclinical
  • HEK293 Cells
  • Humans
  • Liver X Receptors / drug effects*
  • Liver X Receptors / genetics
  • Mice
  • Tetrahydronaphthalenes / pharmacology*
  • Tretinoin / pharmacology*


  • Liver X Receptors
  • Tetrahydronaphthalenes
  • Alitretinoin
  • Tretinoin
  • Bexarotene