Discovery of tetrahydro-cyclopenta[b]indole as selective LXRs modulator

Identification of Novel Liver X Receptor Activators by Structure-Based Modeling

“…10 Although the hydrogen bond was described as critical, LXR modulators are known which do not establish a hydrogen bond to His435. 40 Small ligands, like compound 2 , fill the C1 and C2 region. The benzylsulfonate moiety extends a little into a wide tunnel, which is also present in the binding pocket with bound endogenous ligand.…”

Lipoproteins and Cancer

“…A new ACAT1-specific inhibitor was effective in killing glioma cells in in vitro studies (Bemlih, Poirier et al 2010). LXR pathway modulators that can increase cholesterol efflux and HDL-C levels without stimulating lipid biosynthesis in the liver, needed to treat cardiovascular disease and metabolic syndrome, may also be useful in cancer (Ratni, Blum-Kaelin et al 2009). Dietary regimens targeting fat and cholesterol reduction in those with hyperlipidemia, with known benefits in preventing and treating heart disease, may be recommended to decrease the risk or recurrence of some types of cancer.…”

Orphan nuclear receptors as drug targets for the treatment of prostate and breast cancers

“…Both T0901317 and GW3965 are agonists for both LXRa and LXRb. While the development of selective activators for LXRa and LXRb has been difficult due to their highly similar amino acid sequence (74%), several recent studies have described compounds that display partial selectivity to LXRb [94][95][96][97]. Overall, although challenging, the abundance of existing compounds and crystal structures should facilitate both ligand-and structure-based rational drug design efforts against LXRa and LXRb.…”