title: Discovery and optimization of a novel series of liver X receptor-alpha agonists.
abstract: A novel series of hexafluorocarbinols were discovered as potent activators of the liver X receptor-alpha using a fluorescence polarization assay. Structure-activity relationship study led to the identification of compounds that are more potent agonists than the endogenous ligand, 24(S), 25-epoxycholesterol, with similar efficacy. Several compounds, including T0901317, were shown to have desirable pharmacokinetic profiles suitable for in vivo studies.
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA. leping1@amgen.com
authors.forename: Leping
authors.initials: L
authors.lastname: Li
authors.forename: Jiwen
authors.initials: J
authors.lastname: Liu
authors.forename: Liusheng
authors.initials: L
authors.lastname: Zhu
authors.forename: Serena
authors.initials: S
authors.lastname: Cutler
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Bei
authors.initials: B
authors.lastname: Shan
authors.forename: Julio C
authors.initials: JC
authors.lastname: Medina
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002784:Cholesterol / Q000031:analogs & derivatives / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000819:agonists*; D005454:Fluorescence Polarization; D006845:Hydrocarbons, Fluorinated; D008024:Ligands; D000071518:Liver X Receptors; D008297:Male; D015394:Molecular Structure; D057093:Orphan Nuclear Receptors; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D002784:Cholesterol; D004268:DNA-Binding Proteins; D006845:Hydrocarbons, Fluorinated; D008024:Ligands; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D013449:Sulfonamides; C000605215:Nr1h3 protein, rat; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides; C028358:24,25-epoxycholesterol