Journal
NATURE REVIEWS DRUG DISCOVERY
Volume 8, Issue 1, Pages 41-54Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nrd2760
Keywords
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Funding
- NIDA NIH HHS [R01 DA023926-01, R01 DA023926] Funding Source: Medline
- NIMH NIH HHS [R01 MH073676-01A1, R01 MH074953, R01 MH062646-07, R01 MH074953-01A1, R01 MH062646, R01 MH073676] Funding Source: Medline
- NINDS NIH HHS [R01 NS031373-12A1, R01 NS031373, R01 NS031373-13] Funding Source: Medline
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH074953, R01MH073676, R01MH062646] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS031373] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [R01DA023926] Funding Source: NIH RePORTER
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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.
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