Abstract
1-Substituted benzotriazole carboxylic acids have been identified as the first reported examples of selective small-molecule agonists of the human orphan G-protein-coupled receptor GPR109b (HM74), a low-affinity receptor for the HDL-raising drug niacin. No activity was observed at the highly homologous high-affinity niacin receptor GPR109a (HM74A). The high degree of selectivity was attributed to a difference in the amino acid sequence adjacent to a key arginine-ligand interaction allowing somewhat larger ligands to be tolerated by GPR109b.
MeSH terms
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Adipocytes / drug effects
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Adipocytes / metabolism
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Binding Sites
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Carboxylic Acids / chemical synthesis*
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Carboxylic Acids / chemistry
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Carboxylic Acids / pharmacology
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Cyclic AMP / biosynthesis
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Humans
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Hypolipidemic Agents / chemical synthesis*
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Hypolipidemic Agents / chemistry
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Hypolipidemic Agents / pharmacology
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Ligands
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Lipolysis / drug effects
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Niacin / pharmacology
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Receptors, G-Protein-Coupled / agonists*
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Receptors, Nicotinic
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Structure-Activity Relationship
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Triazoles / chemical synthesis*
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Triazoles / chemistry
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Triazoles / pharmacology
Substances
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Carboxylic Acids
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HCAR2 protein, human
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HCAR3 protein, human
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Hypolipidemic Agents
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Ligands
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Receptors, G-Protein-Coupled
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Receptors, Nicotinic
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Triazoles
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Niacin
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Cyclic AMP