Abstract
A series of potent and binding selective LXRbeta agonists was developed using the previously reported non-selective LXR ligand WAY-254011 as a structural template. With the aid of molecular modeling, it was found that 2,3-diMe-Ph, 2,5-diMe-Ph, and naphthalene substituted quinoline acetic acids (such as quinoline 33, 37, and 38) showed selectivity for LXRbeta over LXRalpha in binding assays.
MeSH terms
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Animals
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Carboxylic Acids / chemistry*
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Carboxylic Acids / metabolism*
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Carboxylic Acids / pharmacology
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Crystallography, X-Ray
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DNA-Binding Proteins / agonists*
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / metabolism
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Gene Expression
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Humans
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Ligands
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Liver X Receptors
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Macrophages / drug effects
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Macrophages / metabolism
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Mice
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Models, Molecular
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Orphan Nuclear Receptors
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Quinolines / chemistry*
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Quinolines / metabolism*
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Quinolines / pharmacology
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Receptors, Cytoplasmic and Nuclear / agonists*
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Receptors, Cytoplasmic and Nuclear / chemistry
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Receptors, Cytoplasmic and Nuclear / metabolism
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Substrate Specificity
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Transcriptional Activation
Substances
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Carboxylic Acids
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DNA-Binding Proteins
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Ligands
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Liver X Receptors
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NR1H3 protein, human
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Nr1h3 protein, mouse
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Orphan Nuclear Receptors
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Quinolines
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Receptors, Cytoplasmic and Nuclear