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.
MeSH terms
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ATP Binding Cassette Transporter 1
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ATP-Binding Cassette Transporters / genetics
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ATP-Binding Cassette Transporters / metabolism
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Cell Line
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DNA-Binding Proteins / agonists*
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Gene Expression Regulation / drug effects*
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Gene Expression Regulation / physiology
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Humans
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Indoles / chemical synthesis
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Indoles / pharmacology*
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Liver X Receptors
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Macrophages / drug effects*
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Macrophages / metabolism
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Models, Chemical
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Monocytes / cytology
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Monocytes / drug effects*
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Orphan Nuclear Receptors
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Receptors, Cytoplasmic and Nuclear / agonists*
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Sterol Regulatory Element Binding Protein 1 / genetics
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Sterol Regulatory Element Binding Protein 1 / metabolism
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Structure-Activity Relationship
Substances
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ABCA1 protein, human
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ATP Binding Cassette Transporter 1
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ATP-Binding Cassette Transporters
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DNA-Binding Proteins
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Indoles
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Liver X Receptors
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Orphan Nuclear Receptors
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Receptors, Cytoplasmic and Nuclear
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Sterol Regulatory Element Binding Protein 1