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PMID: 19116626 Published · ppublish English Journal Article Review

Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders.

Nature reviews. Drug discovery ·Vol. 8 ·No. 1 ·2009-01-00 ·Pages 41-54

Conn PJ, Christopoulos A, Lindsley CW

Abstract

Despite G-protein-coupled receptors (GPCRs) being among the most fruitful targets for marketed drugs, intense discovery efforts for several GPCR subtypes have failed to deliver selective drug candidates. Historically, drug discovery programmes for GPCR ligands have been dominated by efforts to develop agonists and antagonists that act at orthosteric sites for endogenous ligands. However, in recent years, there have been tremendous advances in the discovery of novel ligands for GPCRs that act at allosteric sites to regulate receptor function. These compounds provide high selectivity, novel modes of efficacy and may lead to novel therapeutic agents for the treatment of multiple psychiatric and neurological human disorders.

MeSH Terms
Allosteric Regulation Animals Central Nervous System Diseases/drug therapy Drug Design Drug Evaluation, Preclinical Humans Ligands Receptors, G-Protein-Coupled/antagonists & inhibitors
Chemicals
Ligands Receptors, G-Protein-Coupled
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Conn P Jeffrey
Department of Pharmacology, Vanderbilt Program in Drug Discovery, Vanderbilt Medical Center, 1215 Light Hall, Nashville, Tennessee 37232, USA. [email protected]
Christopoulos Arthur
Lindsley Craig W
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Article Info
Journal
Nature reviews. Drug discovery
Abbr.
Nat Rev Drug Discov
ISSN
1474-1784
DOI
10.1038/nrd2760
Email
[email protected]
Published
2009-01-00
Pages
41-54
Language
English
Region
England
NLM ID
101124171
PMCID
PMC2907734
Subset
IM
Grants
NIMH NIH HHS · R01 MH062646 · United States
NIDA NIH HHS · R01 DA023926 · United States
NINDS NIH HHS · R01 NS031373-12A1 · United States
NIMH NIH HHS · R01 MH062646-07 · United States
NIMH NIH HHS · R01 MH073676 · United States
NIDA NIH HHS · R01 DA023926-01 · United States
NIMH NIH HHS · R01 MH074953 · United States
NIMH NIH HHS · R01 MH074953-01A1 · United States
NINDS NIH HHS · R01 NS031373-13 · United States
NIMH NIH HHS · R01 MH073676-01A1 · United States
NINDS NIH HHS · R01 NS031373 · United States
External Links
PubMed source DOI: 10.1038/nrd2760 PMC Full Text View journal details
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