Synthesis and biological activity of fluorinated analogues of the DAF-12 receptor antagonist 24-hydroxy-4-cholen-3-one.

The DAF-12 receptor is a ligand-activated transcription factor that in its ligand-bound form allows the expression of target genes needed to support the reproductive life cycle of the free-living nematode Caenorhabditis elegans, whereas unbound DAF-12 receptor leads to the developmentally arrested "dauer larvae", specialized for survival and dispersal. The endogenous ligands of the DAF-12 receptor are 3-keto-cholestenoic acids dubbed dafachronic acids. In a previous publication we reported that oxysterols with a shorter side chain (C) modulate the DAF-12 receptor activity either as partial agonists or, in the case of the C alcohol 24-hydroxy-4-cholen-3-one, as an antagonist both in vitro and in vivo.

Fluorinated oxysterol analogues: Synthesis, molecular modelling and LXRβ activity.

Liver X receptors (LXRs) are nuclear receptors that play central roles in the transcriptional control of lipid metabolism. The ability of LXRs to integrate metabolic and inflammation signalling makes them attractive targets for intervention in human metabolic diseases. Several oxidized metabolites of cholesterol (oxysterols) are endogenous LXR ligands, that modulate their transcriptional responses.