Abstract
Using an mGluR2 FRET-based binding assay, binders of the transmembrane region devoid of functional activity were identified. It is reported that slight chemical modifications of these SAMs can dramatically change activity of the resulting analogues without altering their affinities. Starting from compound 1, three mGluR2 NAMs showing also mGluR3 PAM activities were obtained. SAMs therefore represent a useful approach to explore the chemical space for GPCR allosteric modulator identification.
MeSH terms
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Allosteric Regulation
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Benzopyrans / chemical synthesis*
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Benzopyrans / chemistry
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Benzopyrans / pharmacology
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Calcium / metabolism
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Cell Line
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Excitatory Amino Acid Agents / chemical synthesis*
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Excitatory Amino Acid Agents / chemistry
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Excitatory Amino Acid Agents / pharmacology
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Fluorescence Resonance Energy Transfer
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High-Throughput Screening Assays
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Humans
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Receptors, Metabotropic Glutamate / physiology*
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Small Molecule Libraries
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Structure-Activity Relationship
Substances
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Benzopyrans
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Excitatory Amino Acid Agents
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Receptors, Metabotropic Glutamate
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Small Molecule Libraries
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metabotropic glutamate receptor 2
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metabotropic glutamate receptor 3
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Calcium