title: Ligands of Therapeutic Utility for the Liver X Receptors.
abstract: Liver X receptors (LXRs) have been increasingly recognized as a potential therapeutic target to treat pathological conditions ranging from vascular and metabolic diseases, neurological degeneration, to cancers that are driven by lipid metabolism. Amidst intensifying efforts to discover ligands that act through LXRs to achieve the sought-after pharmacological outcomes, several lead compounds are already being tested in clinical trials for a variety of disease interventions. While more potent and selective LXR ligands continue to emerge from screening of small molecule libraries, rational design, and empirical medicinal chemistry approaches, challenges remain in minimizing undesirable effects of LXR activation on lipid metabolism. This review provides a summary of known endogenous, naturally occurring, and synthetic ligands. The review also offers considerations from a molecular modeling perspective with which to design more specific LXRβ ligands based on the interaction energies of ligands and the important amino acid residues in the LXRβ ligand binding domain.
authors.affiliation: Department of Chemistry and RCMI Cancer Research Center, Xavier University of Louisiana, New Orleans, LA 70125, USA. rkomati@xula.edu.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Komati
authors.affiliation: Department of Chemistry and RCMI Cancer Research Center, Xavier University of Louisiana, New Orleans, LA 70125, USA. dspadoni@xula.edu.
authors.forename: Dominick
authors.initials: D
authors.lastname: Spadoni
authors.affiliation: Department of Chemistry and RCMI Cancer Research Center, Xavier University of Louisiana, New Orleans, LA 70125, USA. szheng@xula.edu.
authors.forename: Shilong
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Chemistry and RCMI Cancer Research Center, Xavier University of Louisiana, New Orleans, LA 70125, USA. jsridhar@xula.edu.
authors.forename: Jayalakshmi
authors.initials: J
authors.lastname: Sridhar
authors.affiliation: Department of Chemistry and RCMI Cancer Research Center, Xavier University of Louisiana, New Orleans, LA 70125, USA. kriley3@xula.edu.
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Riley
authors.affiliation: Department of Chemistry and RCMI Cancer Research Center, Xavier University of Louisiana, New Orleans, LA 70125, USA. gwang@xula.edu.
authors.forename: Guangdi
authors.initials: G
authors.lastname: Wang
mesh_terms: D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008024:Ligands; D050356:Lipid Metabolism / Q000187:drug effects* / Q000502:physiology; D008099:Liver / Q000378:metabolism; D000071518:Liver X Receptors / Q000819:agonists*; D008659:Metabolic Diseases / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy; D009422:Nervous System Diseases / Q000188:drug therapy; D000072376:Oxysterols / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D014652:Vascular Diseases / Q000188:drug therapy
chemical_list: D008024:Ligands; D000071518:Liver X Receptors; D000072376:Oxysterols; D018160:Receptors, Cytoplasmic and Nuclear
keywords: Alzheimer’s disease; LXRα; LXRβ specific ligands; atherosclerosis; cancer; diabetes; interaction energy; lipid metabolism; liver X receptors; molecular modeling