NDLI: Potent Prearranged Positive Allosteric Modulators of the Glucagon-like Peptide-1 Receptor

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Potent Prearranged Positive Allosteric Modulators of the Glucagon-like Peptide-1 Receptor

Content Provider	Scilit
Author	Jones, Ben J. Scopelliti, Rosario Tomas, Alejandra Bloom, Stephen R. Hodson, David J. Broichhagen, Johannes
Copyright Year	2017
Description	Journal: ChemistryOpen Drugs that allosterically modulate G protein‐coupled receptor (GPCR) activity display higher specificity and may improve disease treatment. However, the rational design of compounds that target the allosteric site is difficult, as conformations required for receptor activation are poorly understood. Guided by photopharmacology, a set of prearranged positive allosteric modulators (PAMs) with restricted degrees of freedom was designed and tested against the glucagon‐like peptide‐1 receptor (GLP‐1R), a GPCR involved in glucose homeostasis. Compounds incorporating a trans‐stilbene comprehensively outperformed those with a cis‐stilbene, as well as the benchmark BETP, as GLP‐1R PAMs. We also identified major effects of ligand conformation on GLP‐1R binding kinetics and signal bias. Thus, we describe a photopharmacology‐directed approach for rational drug design, and introduce a new class of stilbene‐containing PAM for the specific regulation of GPCR activity.
Related Links	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5542757/pdf
Ending Page	505
Page Count	5
Starting Page	501
e-ISSN	21911363
DOI	10.1002/open.201700062
Journal	ChemistryOpen
Issue Number	4
Volume Number	6
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2017-06-05
Access Restriction	Open
Subject Keyword	Journal: ChemistryOpen Medicinal Chemistry Glucagon-like Peptides Glucagon-like Peptide-1 Receptors G Protein-coupled Receptors
Content Type	Text
Resource Type	Article

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