Abstract
A series of novel indole-based PPAR agonists is described leading to discovery of 10k, a highly potent PPAR pan-agonist. The structural biology and molecular docking studies revealed that the distances between the acidic group and the linker, when a ligand was complexed with PPARgamma protein, were important for the potent activity. The hydrophobic tail part of 10k makes intensive hydrophobic interaction with the PPARgamma protein resulting in potent activity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding Sites
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Crystallography, X-Ray
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Drug Design
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Hydrophobic and Hydrophilic Interactions
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Indoleacetic Acids / chemical synthesis*
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Indoleacetic Acids / chemistry
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Ligands
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Models, Molecular*
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Naphthalenes / chemical synthesis*
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Naphthalenes / chemistry
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PPAR gamma / agonists*
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PPAR gamma / chemistry*
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Structure-Activity Relationship
Substances
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2-(5-(3-(6-benzoyl-1-propylnaphthalene-2-yloxy)propoxy)indol-1-yl)ethanoic acid
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Indoleacetic Acids
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Ligands
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Naphthalenes
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PPAR gamma