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

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Jeffrey Conn, P., Christopoulos, Arthur, Lindsley, Craig W.·2009·Nature Reviews Drug Discovery

DOI 10.1038/nrd2760PMC PMC2907734

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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.

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Can the pharmaceutical industry reduce attrition rates?
Kola, I., & Landis, J. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1470 · Cited by 4,167
PHARMACOLOGY AND FUNCTIONS OF METABOTROPIC GLUTAMATE RECEPTORS
Conn, P. J., & Pin, J. (1997) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.37.1.205 · Cited by 3,083
The Ecology of Freshwater Phytoplankton.
Jones, R. I., & REYNOLDS, C. S. (1985) · Journal of Ecology · doi:10.2307/2260522 · Cited by 2,817
The mGluR theory of fragile X mental retardation
Bear, M. F., Huber, K. M., & Warren, S. T. (2004) · Trends in Neurosciences · doi:10.1016/j.tins.2004.04.009 · Cited by 1,580
G Protein-coupled Receptors
Ji, T. H., Grossmann, M., & Ji, I. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.28.17299 · Cited by 1,281
Maraviroc (UK-427,857), a Potent, Orally Bioavailable, and Selective Small-Molecule Inhibitor of Chemokine Receptor CCR5 with Broad-Spectrum Anti-Human Immunodeficiency Virus Type 1 Activity
Dorr, P. K., Westby, M., Dobbs, S., Griffin, P., Irvine, B., Macartney, M. J., Mori, J., Rickett, G., Smith‐Burchnell, C., Napier, C. M., et al. (2005) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.49.11.4721-4732.2005 · Cited by 1,154
Functional Selectivity and Classical Concepts of Quantitative Pharmacology
Urban, J. D., Clarke, W. P., von Zastrow, M., Nichols, D. E., Kobilka, B. K., Weinstein, H., Javitch, J. A., Roth, B. L., Christopoulos, A., Sexton, P. M., et al. (2006) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.106.104463 · Cited by 1,131
Self-citation
Operational models of pharmacological agonism
Black, J. W., & Leff, P. (1983) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.1983.0093 · Cited by 1,106
Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized Phase 2 clinical trial
Patil, S. T., Zhang, L., Martenyi, F., Lowe, S. L., Jackson, K. A., Andreev, B. V., Avedisova, A. S., Bardenstein, L. M., Gurovich, I. Y., Morozova, M. A., et al. (2007) · Nature Medicine · doi:10.1038/nm1632 · Cited by 1,040
Reversal of Phencyclidine Effects by a Group II Metabotropic Glutamate Receptor Agonist in Rats
Moghaddam, B., & Adams, B. W. (1998) · Science · doi:10.1126/science.281.5381.1349 · Cited by 1,006

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Swanson, C. J., Bures, M., Johnson, M. P., Linden, A. M., Monn, J. A. & Schoepp, D. D. Metabotropic glutamate receptors as novel targets for anxiety and stress disorders. Nature Rev. Drug Discov. 4, 131–144 (2005). · DOI · Paper page
Baez, M. et al. Molecular mapping of a subtype selective site for positive allosteric modulation of the mGlu2 receptor. Neuropharmacol. Abstr. 43, 274–275 (2002).

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Authors: Jeffrey Conn, P., Christopoulos, A., & Lindsley, C. W.
Affiliations: Monash University (AU)
Vanderbilt University (US)
ORCID: Christopoulos, Arthur
Lindsley, Craig W.
Venue: Nature Reviews Drug Discovery
Publisher: Springer Science and Business Media LLC
Published: 2009-01
Volume: 8
Issue: 1
Pages: 41-54
ISSN: 1474-1776 (ISSN-L)
1474-1784
DOI: 10.1038/nrd2760
PMC: PMC2907734
OpenAlex: W2003736358
Cited by: 1,063
References: 139
Citations by year: 2026: 30 · 2025: 46 · 2024: 37 · 2023: 25 · 2022: 48 · 2021: 51 · 2020: 44 · 2019: 58 · 2018: 57 · 2017: 68 · 2016: 64 · 2015: 67 · 2014: 69 · 2013: 80 · 2012: 75
FWCI: 6.60
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature Reviews Drug Discovery (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Mental Health (R01MH073676, R01MH074953, R01MH062646)
National Institute on Drug Abuse (R01DA023926)
National Institute of Neurological Disorders and Stroke (R01NS031373)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords: G protein-coupled receptors, allosteric modulators, allosteric site, orthosteric ligands, mental illness, neurological disorders, CNS drug discovery, receptor selectivity, novel therapeutic agents
MeSH terms: Allosteric Regulation, Animals, Central Nervous System Diseases, Drug Evaluation, Preclinical, Humans, Ligands, Drug Design, Receptors, G-Protein-Coupled

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

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