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Nat Rev Drug Discov. 2014 Sep;13(9):692-708. doi: 10.1038/nrd4308.

Opportunities and challenges in the discovery of allosteric modulators of GPCRs for treating CNS disorders.

Author information

1
Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, Tennessee 1215D LH, USA.
2
Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37232, USA.

Abstract

Novel allosteric modulators of G protein-coupled receptors (GPCRs) are providing fundamental advances in the development of GPCR ligands with high subtype selectivity and novel modes of efficacy that have not been possible with traditional approaches. As new allosteric modulators are advancing as drug candidates, we are developing an increased understanding of the major advantages and broad range of activities that can be achieved with these agents through selective modulation of specific signalling pathways, differential effects on GPCR homodimers versus heterodimers, and other properties. This understanding creates exciting opportunities, as well as unique challenges, in the optimization of novel therapeutic agents for disorders of the central nervous system.

PMID:
25176435
PMCID:
PMC4208620
DOI:
10.1038/nrd4308
[Indexed for MEDLINE]
Free PMC Article

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