title: Discovery of a new binding mode for a series of liver X receptor agonists.
abstract: Structural modification of a series of dual LXRα/β agonists led to the identification of a new class of LXRβ partial agonists. An X-ray co-crystal structure shows that a representative member of this series, pyrrole 5, binds to LXRβ with a reversed orientation compared to 1.
authors.affiliation: Department of Medicinal Chemistry, Amgen Inc., 1120 Veterans Blvd., South San Francisco, CA 94080, USA. dkopecky@amgen.com
authors.forename: David J
authors.initials: DJ
authors.lastname: Kopecky
authors.forename: Xian Yun
authors.initials: XY
authors.lastname: Jiao
authors.forename: Ben
authors.initials: B
authors.lastname: Fisher
authors.forename: Sharon
authors.initials: S
authors.lastname: McKendry
authors.forename: Marc
authors.initials: M
authors.lastname: Labelle
authors.forename: Derek E
authors.initials: DE
authors.lastname: Piper
authors.forename: Peter
authors.initials: P
authors.lastname: Coward
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Shiau
authors.forename: Patrick
authors.initials: P
authors.lastname: Escaron
authors.forename: Jean
authors.initials: J
authors.lastname: Danao
authors.forename: Anne
authors.initials: A
authors.lastname: Chai
authors.forename: Juan
authors.initials: J
authors.lastname: Jaen
authors.forename: Frank
authors.initials: F
authors.lastname: Kayser
mesh_terms: D001665:Binding Sites; D018938:Caco-2 Cells; D018360:Crystallography, X-Ray; D017930:Genes, Reporter; D057809:HEK293 Cells; D006801:Humans; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors / Q000819:agonists* / Q000737:chemistry; D011485:Protein Binding; D020033:Protein Isoforms / Q000819:agonists* / Q000737:chemistry; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D020033:Protein Isoforms; D011758:Pyrroles