title: Steroidal and triterpenoidal fungal metabolites as ligands of liver X receptors.
abstract: Cholesterol homeostasis is tightly controlled process that involves a variety of regulators including liver X receptors (LXR). Agonists of LXR are expected to increase cholesterol efflux, lower LDL, and raise HDL levels. Screening of a natural product library of microbial extracts using a LXR-scintillation proximity assay (SPA) binding assay and bioassay-guided fractionation of a number of fungal extracts led to the isolation of five ergostane and a cycloartane derivative. These compounds exhibited IC50 value ranging 0.5 approximately 9 microM in the binding assay for a-receptor and a number of these showed in vitro agonist activity in the coactivator association assays but lacked the cell based LXR activation. The isolation and LXR activity of these compounds are described.
authors.affiliation: Merck Research Laboratories, P. O. Box 2000, Rahway, New Jersey 07065, USA.
authors.forename: John G
authors.initials: JG
authors.lastname: Ondeyka
authors.forename: Hiranthi
authors.initials: H
authors.lastname: Jayasuriya
authors.forename: Kithsiri B
authors.initials: KB
authors.lastname: Herath
authors.forename: Ziqiang
authors.initials: Z
authors.lastname: Guan
authors.forename: Marvin
authors.initials: M
authors.lastname: Schulman
authors.forename: Javier
authors.initials: J
authors.lastname: Collado
authors.forename: Anne W
authors.initials: AW
authors.lastname: Dombrowski
authors.forename: Soojin S
authors.initials: SS
authors.lastname: Kwon
authors.forename: Christine
authors.initials: C
authors.lastname: McCallum
authors.forename: Neelam
authors.initials: N
authors.lastname: Sharma
authors.forename: Karen
authors.initials: K
authors.lastname: MacNaul
authors.forename: Nancy
authors.initials: N
authors.lastname: Hayes
authors.forename: John G
authors.initials: JG
authors.lastname: Menke
authors.forename: Sheo B
authors.initials: SB
authors.lastname: Singh
mesh_terms: D004268:DNA-Binding Proteins / Q000819:agonists* / Q000378:metabolism; D005658:Fungi / Q000737:chemistry / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D008024:Ligands; D008099:Liver / Q000378:metabolism; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000378:metabolism; D013256:Steroids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology
chemical_list: D004268:DNA-Binding Proteins; D008024:Ligands; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D013256:Steroids; D014315:Triterpenes