title: Discovery and structure-activity relationship studies of indole derivatives as liver X receptor (LXR) agonists.
abstract: A structurally novel liver X receptor (LXR) agonist (1) was identified from internal compound collection utilizing the combination of structure-based virtual screening and high-throughput gene profiling. Compound 1 increased ABCA1 gene expression by eightfold and SREBP1c by threefold in differentiated THP-1 macrophage cell lines. Confirmation of its agonistic activity against LXR was obtained in the co-factor recruitment and reporter transactivation assays. Structure-activity relationship studies on compound 1 are described.
authors.affiliation: Department of Chemistry, Tanabe Research Laboratories USA, Inc., 4540 Towne Centre Court, San Diego, CA 92121, USA.
authors.forename: Farid
authors.initials: F
authors.lastname: Bakir
authors.forename: Sunil
authors.initials: S
authors.lastname: Kher
authors.forename: Madhavi
authors.initials: M
authors.lastname: Pannala
authors.forename: Norma
authors.initials: N
authors.lastname: Wilson
authors.forename: Trang
authors.initials: T
authors.lastname: Nguyen
authors.forename: Ila
authors.initials: I
authors.lastname: Sircar
authors.forename: Kei
authors.initials: K
authors.lastname: Takedomi
authors.forename: Chiaki
authors.initials: C
authors.lastname: Fukushima
authors.forename: James
authors.initials: J
authors.lastname: Zapf
authors.forename: Kui
authors.initials: K
authors.lastname: Xu
authors.forename: Shao-Hui
authors.initials: SH
authors.lastname: Zhang
authors.forename: Juping
authors.initials: J
authors.lastname: Liu
authors.forename: Lisa
authors.initials: L
authors.lastname: Morera
authors.forename: Lisa
authors.initials: L
authors.lastname: Schneider
authors.forename: Naoki
authors.initials: N
authors.lastname: Sakurai
authors.forename: Rick
authors.initials: R
authors.lastname: Jack
authors.forename: Jie-Fei
authors.initials: JF
authors.lastname: Cheng
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000819:agonists*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology*; D000071518:Liver X Receptors; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008956:Models, Chemical; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D004268:DNA-Binding Proteins; D007211:Indoles; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D051780:Sterol Regulatory Element Binding Protein 1