Synthetic ligands selective for LXRβ over LXRα, identification and methods of use thereof

LXR nuclear receptor agonists have been previously shown to increase cholesterol efflux, raise plasma HDL cholesterol, stimulate cholesterol excretion, and reduce atherosclerotic lesions. However, these agonists have also been associated with the unwanted side effect of hypertriglyeridemia. This hypertriglyeridemia appears to be mediated by the LXRα subtype rather than LXRβ, which suggests that LXRβ-selective agonists are attractive candidates for modulation of human lipid metabolism. The present application provides novel LXRβ-selective ligands that preferably modulate LXRβ over LXRα. These ligands may be used to treat a variety of diseases associated with LXR, such as for example lipid metabolism disorders, atherosclerosis, Alzheimer disease, and inflammation.