Abstract
The H1R antagonist astemizole was identified as a somatostatin 5 (SST5) receptor antagonist by a comparative sequence analysis of the consensus drug binding pocket of GPCRs. Subsequently, a similarity analysis of GPCR affinity profiles of astemizole versus a set of in-house GPCR-biased combinatorial libraries revealed new chemical entry points that led to a second lead series with nanomolar binding affinity.
MeSH terms
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Astemizole / chemistry*
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Astemizole / pharmacology
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Binding Sites
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Combinatorial Chemistry Techniques
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Databases, Factual
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Histamine H1 Antagonists / chemistry*
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Histamine H1 Antagonists / pharmacology
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Humans
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Piperidines / chemical synthesis*
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Piperidines / chemistry
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Piperidines / pharmacology
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Receptors, G-Protein-Coupled / chemistry*
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Receptors, G-Protein-Coupled / genetics*
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Receptors, G-Protein-Coupled / metabolism
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Receptors, Somatostatin / antagonists & inhibitors*
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Receptors, Somatostatin / chemistry
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Receptors, Somatostatin / genetics
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Spiro Compounds / chemical synthesis*
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Spiro Compounds / chemistry
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Spiro Compounds / pharmacology
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Structure-Activity Relationship
Substances
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Histamine H1 Antagonists
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Piperidines
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Receptors, G-Protein-Coupled
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Receptors, Somatostatin
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Spiro Compounds
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Astemizole
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somatostatin receptor 5