Therapeutics: Liver X receptor (LXR)

Cell culture and mouse studies identified an LXR inverse agonist that could help treat cancer. Optimization and in vitro testing of a previously reported LXR inverse agonist produced a compound that inhibited LXR-dependent transcription in HEK cells at nanomolar IC50 values and decreased activation of lipogenic and glycolytic LXR target genes in human liver cancer cells compared with vehicle. In human lung, colon, prostate and pancreatic cancer cell lines, the compound inhibited cell growth with IC50 values of 15-104 nM. In mouse xenograft models of colon, prostate or lung cancer, the compound decreased tumor growth compared with vehicle. Next steps include optimization of the compound for oral bioavailability...