Cited by 1,063Receptor Mechanisms and SignalingNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

The DOI matches its Crossref record; 139 of the 139 references it cites were found in a registry or an index.

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

Open access

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

DOI 10.1038/nrd2760PMC PMC2907734

Open this paper in CoChat — free account

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1038/nrd2760

Cites

139 of 139 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

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

Show all 139 references

Research works printed but not linked: 2

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).

Sorted by citations

Molecular Dynamics Simulation for All
Hollingsworth, S. A., & Dror, R. O. (2018) · Neuron · doi:10.1016/j.neuron.2018.08.011 · Cited by 3,522
The structure and function of G-protein-coupled receptors
Rosenbaum, D. M., Rasmussen, S. G. F., & Kobilka, B. K. (2009) · Nature · doi:10.1038/nature08144 · Cited by 2,534
“This high conservation in the ligand-binding pocket is also observed in other subfamilies of GPCRs (such as dopamine, serotonin and histamine), and probably explains some of the difficulty in obtaining potent subtype-selective compounds in pharmaceutical discovery program”
Computational Methods in Drug Discovery
Sliwoski, G. R., Kothiwale, S., Meiler, J., & Lowe, E. W. (2013) · Pharmacological Reviews · doi:10.1124/pr.112.007336 · Cited by 2,306
How were new medicines discovered?
Swinney, D. C., & Anthony, J. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3480 · Cited by 1,812
Role of Molecular Dynamics and Related Methods in Drug Discovery
Vivo, M. D., Masetti, M., Bottegoni, G., & Cavalli, A. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b01684 · Cited by 1,358
International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and Classification of Adenosine Receptors—An Update
Fredholm, B. B., IJzerman, A. P., Jacobson, K. A., Linden, J. M., & Müller, C. E. (2011) · Pharmacological Reviews · doi:10.1124/pr.110.003285 · Cited by 1,307
GPCR Dynamics: Structures in Motion
Latorraca, N. R., Venkatakrishnan, A., & Dror, R. O. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.6b00177 · Cited by 861
Structure of an Agonist-Bound Human A 2A Adenosine Receptor
Xu, F., Wu, H., Katritch, V., Han, G. W., Jacobson, K. A., Gao, Z., Cherezov, V., & Stevens, R. C. (2011) · Science · doi:10.1126/science.1202793 · Cited by 820
Allostery in Disease and in Drug Discovery
Nussinov, R., & Tsai, C. (2013) · Cell · doi:10.1016/j.cell.2013.03.034 · Cited by 769
Pathway and mechanism of drug binding to G-protein-coupled receptors
Dror, R. O., Pan, A. C., Arlow, D. H., Borhani, D. W., Maragakis, P., Shan, Y., Xu, H., & Shaw, D. E. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1104614108 · Cited by 737
Excitotoxicity: Bridge to various triggers in neurodegenerative disorders
Mehta, A., Prabhakar, M., Kumar, P., Deshmukh, R. R., & Sharma, P. L. (2012) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2012.10.032 · Cited by 678
Ligand binding assays at equilibrium: validation and interpretation
Hulme, E. C., & Trevethick, M. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00604.x · Cited by 687
Mutations causing syndromic autism define an axis of synaptic pathophysiology
Auerbach, B. D., Osterweil, E. K., & Bear, M. F. (2011) · Nature · doi:10.1038/nature10658 · Cited by 592
Emerging principles in protease-based drug discovery
Drąg, M., & Salvesen, G. S. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3053 · Cited by 605
Seven Transmembrane Receptors as Shapeshifting Proteins: The Impact of Allosteric Modulation and Functional Selectivity on New Drug Discovery
Kenakin, T., & Miller, L. J. (2010) · Pharmacological Reviews · doi:10.1124/pr.108.000992 · Cited by 584
G Protein–Coupled Receptor Oligomerization Revisited: Functional and Pharmacological Perspectives
Ferré, S., Casadó, V., Devi, L. A., Filizola, M., Jockers, R., Lohse, M. J., Milligan, G., Pin, J., & Guitart, X. (2014) · Pharmacological Reviews · doi:10.1124/pr.113.008052 · Cited by 574
The changing opioid crisis: development, challenges and opportunities
Volkow, N. D., & Blanco, C. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0661-4 · Cited by 594
Ligand-specific regulation of the extracellular surface of a G-protein-coupled receptor
Bokoch, M. P., Zou, Y., Rasmussen, S. G. F., Liu, C. W., Nygaard, R., Rosenbaum, D. M., Fung, J. J., Choi, H., Thian, F. S., Kobilka, T. S., et al. (2010) · Nature · doi:10.1038/nature08650 · Cited by 473
Diversity and modularity of G protein-coupled receptor structures
Katritch, V., Cherezov, V., & Stevens, R. C. (2011) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2011.09.003 · Cited by 480
Muscarinic acetylcholine receptors: novel opportunities for drug development
Kruse, A. C., Kobilka, B. K., Gautam, D., Sexton, P. M., Christopoulos, A., & Wess, J. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4295 · Cited by 437
Self-citation
Conus Venom Peptide Pharmacology
Lewis, R. J., Dutertre, S., Vetter, I., & Christie, M. J. (2012) · Pharmacological Reviews · doi:10.1124/pr.111.005322 · Cited by 434
Structure of class C GPCR metabotropic glutamate receptor 5 transmembrane domain
Dore, A. S., Okrasa, K., Patel, J. C., Serrano‐Vega, M. J., Bennett, K. A., Cooke, R. M., Errey, J. C., Jazayeri, A., Khan, S. A., Tehan, B. G., et al. (2014) · Nature · doi:10.1038/nature13396 · Cited by 420
Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials
Xie, X., Yu, T., Li, X., Zhang, N., Foster, L. J., Peng, C., Huang, W., & He, G. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01589-z · Cited by 396
Design of phosphodiesterase 4D (PDE4D) allosteric modulators for enhancing cognition with improved safety
Burgin, A. B., Magnússon, Ó. Þ., Singh, J., Witte, P., Staker, B. L., Björnsson, J. M., Þorsteinsdóttir, M., Hrafnsdóttir, S., Hagen, T. J., Kiselyov, A. S., et al. (2009) · Nature Biotechnology · doi:10.1038/nbt.1598 · Cited by 396
Allostery and the Monod-Wyman-Changeux Model After 50 Years
Changeux, J. (2012) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-050511-102222 · Cited by 406
The role of serotonin 5-HT2A receptors in memory and cognition
Zhang, G., & Stackman, R. W. (2015) · Frontiers in Pharmacology · doi:10.3389/fphar.2015.00225 · Cited by 398
Therapies for rare diseases: therapeutic modalities, progress and challenges ahead
Tambuyzer, E., Vandendriessche, B., Austin, C. P., Brooks, P. J., Larsson, K., Miller Needleman, K. I., Valentine, J., Davies, K., Groft, S. C., Preti, R., et al. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0049-9 · Cited by 357
Allosteric Modulation as a Unifying Mechanism for Receptor Function and Regulation
Changeux, J., & Christopoulos, A. (2016) · Cell · doi:10.1016/j.cell.2016.08.015 · Cited by 353
Self-citation
Crystal structures of the M1 and M4 muscarinic acetylcholine receptors
Thal, D. M., Sun, B., Feng, D., Nawaratne, V., Leach, K., Felder, C. C., Bures, M. G., Evans, D. A. P., Weis, W. I., Bachhawat, P., et al. (2016) · Nature · doi:10.1038/nature17188 · Cited by 342
Self-citation
Activation of metabotropic glutamate receptors as a novel approach for the treatment of schizophrenia
Conn, P. J., Lindsley, C. W., & Jones, C. K. (2008) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2008.10.006 · Cited by 330
Self-citation
Discovering Anti-Cancer Drugs via Computational Methods
Cui, W., Aouidate, A., Wang, S., Yu, Q., Li, Y.-H., & Yuan, S. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00733 · Cited by 315
Fluorescence/Bioluminescence Resonance Energy Transfer Techniques to Study G-Protein-Coupled Receptor Activation and Signaling
Lohse, M. J., Nuber, S., & Hoffmann, C. (2012) · Pharmacological Reviews · doi:10.1124/pr.110.004309 · Cited by 318
Subtype-selective allosteric modulators of muscarinic receptors for the treatment of CNS disorders
Conn, P. J., Jones, C. K., & Lindsley, C. W. (2009) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2008.12.002 · Cited by 286
Self-citation
Drugs for Allosteric Sites on Receptors
Wenthur, C. J., Gentry, P. R., Mathews, T. P., & Lindsley, C. W. (2011) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010611-134525 · Cited by 285
Self-citation
Homeostatic Scaling Requires Group I mGluR Activation Mediated by Homer1a
Hu, J.-H., Park, J. M., Park, S. J., Xiao, B., Dehoff, M. H., Kim, S., Hayashi, T., Schwarz, M. K., Huganir, R. L., Seeburg, P. H., et al. (2010) · Neuron · doi:10.1016/j.neuron.2010.11.008 · Cited by 263
International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function
Barnes, N. M., Ahern, G. P., Bécamel, C., Bockaert, J., Camilleri, M., Chaumont‐Dubel, S., Claeysen, S., Cunningham, K. A., Fone, K. C. F., Gershon, M. D., et al. (2020) · Pharmacological Reviews · doi:10.1124/pr.118.015552 · Cited by 274
Allosteric modulation of G protein-coupled receptors: A pharmacological perspective
Keov, P., Sexton, P. M., & Christopoulos, A. (2010) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.07.010 · Cited by 265
Self-citation
Opportunities and challenges in the discovery of allosteric modulators of GPCRs for treating CNS disorders
Conn, P. J., Lindsley, C. W., Meiler, J., & Niswender, C. M. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4308 · Cited by 264
Self-citation
Allostery at G Protein-Coupled Receptor Homo- and Heteromers: Uncharted Pharmacological Landscapes
Smith, N. J., & Milligan, G. (2010) · Pharmacological Reviews · doi:10.1124/pr.110.002667 · Cited by 261
Differential hydrogen/deuterium exchange mass spectrometry analysis of protein–ligand interactions
Chalmers, M. J., Busby, S. A., Pascal, B. D., West, G. M., & Griffin, P. R. (2011) · Expert Review of Proteomics · doi:10.1586/epr.10.109 · Cited by 256
Parkinson's Disease Therapeutics: New Developments and Challenges Since the Introduction of Levodopa
Smith, Y., Wichmann, T., Factor, S. A., & DeLong, M. R. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.212 · Cited by 266
International Union of Basic and Clinical Pharmacology. XC. Multisite Pharmacology: Recommendations for the Nomenclature of Receptor Allosterism and Allosteric Ligands
Christopoulos, A., Changeux, J., Catterall, W. A., Fabbro, D., Burris, T. P., Cidlowski, J. A., Olsen, R. W., Peters, J. A., Neubig, R. R., Pin, J., et al. (2014) · Pharmacological Reviews · doi:10.1124/pr.114.008862 · Cited by 246
Self-citation
A Selective Allosteric Potentiator of the M 1 Muscarinic Acetylcholine Receptor Increases Activity of Medial Prefrontal Cortical Neurons and Restores Impairments in Reversal Learning
Shirey-Rice, J. K., Brady, A. E., Jones, P. J., Davis, A. A., Bridges, T. M., Kennedy, J. P., Jadhav, S. B., Menon, U. N., Xiang, Z., Watson, M. L., et al. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.3930-09.2009 · Cited by 237
Self-citation
Structural Modifications that Alter the P-Glycoprotein Efflux Properties of Compounds
Hitchcock, S. A. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm201136z · Cited by 232
Allosteric Modulation of Seven Transmembrane Spanning Receptors: Theory, Practice, and Opportunities for Central Nervous System Drug Discovery
Melancon, B. J., Hopkins, C. R., Wood, M. R., Emmitte, K. A., Niswender, C. M., Christopoulos, A., Conn, P. J., & Lindsley, C. W. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm201139r · Cited by 228
Self-citation
Development of allosteric modulators of GPCRs for treatment of CNS disorders
Nickols, H. H., & Conn, P. J. (2013) · Neurobiology of Disease · doi:10.1016/j.nbd.2013.09.013 · Cited by 232
Muscarinic and Nicotinic Acetylcholine Receptor Agonists and Allosteric Modulators for the Treatment of Schizophrenia
Jones, C. K., Byun, N. E., & Bubser, M. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.199 · Cited by 241
Allosteric Modulation of GPCRs: New Insights and Potential Utility for Treatment of Schizophrenia and Other CNS Disorders
Foster, D. J., & Conn, P. J. (2017) · Neuron · doi:10.1016/j.neuron.2017.03.016 · Cited by 231
Quantifying Correlations Between Allosteric Sites in Thermodynamic Ensembles
McClendon, C. L., Friedland, G. D., Mobley, D. L., Amirkhani, H., & Jacobson, M. P. (2009) · Journal of Chemical Theory and Computation · doi:10.1021/ct9001812 · Cited by 220
Advances in G Protein-Coupled Receptor Allostery: From Function to Structure
Christopoulos, A. (2014) · Molecular Pharmacology · doi:10.1124/mol.114.094342 · Cited by 231
Self-citation
The Significance of G Protein-Coupled Receptor Crystallography for Drug Discovery
Salon, J. A., Lodowski, D. T., & Palczewski, K. (2011) · Pharmacological Reviews · doi:10.1124/pr.110.003350 · Cited by 226
Progress in Structure Based Drug Design for G Protein-Coupled Receptors
Congreve, M., LANGMEAD, C. J., Mason, J. S., & Marshall, F. H. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm200371q · Cited by 218
Biased Allosteric Modulators: New Frontiers in GPCR Drug Discovery
Slosky, L. M., Caron, M. G., & Barak, L. S. (2021) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2020.12.005 · Cited by 214
Molecular mechanism of the sweet taste enhancers
Zhang, F., Klebansky, B., Fine, R., Liu, H., Xu, H., Servant, G., Zoller, M. J., Tachdjian, C., & Li, X. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911660107 · Cited by 207
Allosteric Modulation of Family C G-Protein-Coupled Receptors: from Molecular Insights to Therapeutic Perspectives
Urwyler, S. (2011) · Pharmacological Reviews · doi:10.1124/pr.109.002501 · Cited by 210
mGluR5 Positive Allosteric Modulators Facilitate both Hippocampal LTP and LTD and Enhance Spatial Learning
Ayala, J. E., Chen, Y., Banko, J. L., Sheffler, D. J., Williams, R. D., Telk, A. N., Watson, N. L., Xiang, Z., Zhang, Y., Jones, P. J., et al. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2009.30 · Cited by 206
Self-citation
Novel Allosteric Modulators of G Protein-coupled Receptors
Gentry, P. R., Sexton, P. M., & Christopoulos, A. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.r115.662759 · Cited by 199
Self-citation
Binding and Signaling Studies Disclose a Potential Allosteric Site for Cannabidiol in Cannabinoid CB2 Receptors
Martínez‐Pinilla, E., Varani, K., Reyes‐Resina, I., Angelats, E., Vincenzi, F., Ferreiro‐Vera, C., Oyarzábal, J., Canela, E. I., Lanciego, J. L., Nadal, X., et al. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00744 · Cited by 200
DREADD Agonist 21 Is an Effective Agonist for Muscarinic-Based DREADDs in Vitro and in Vivo
Thompson, K. J., Khajehali, E., Bradley, S. J., Navarrete, J. S., Huang, X., Slocum, S. T., Jin, J. J., Liu, J., Xiong, Y., Olsen, R. H. J., et al. (2018) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.8b00012 · Cited by 200
Self-citation
Protein-protein interaction modulators: advances, successes and remaining challenges
Mabonga, L., & Kappo, A. P. (2019) · Biophysical Reviews · doi:10.1007/s12551-019-00570-x · Cited by 200
Exciting Times beyond the Brain: Metabotropic Glutamate Receptors in Peripheral and Non-Neural Tissues
Julio‐Pieper, M., Flor, P. J., Dinan, T. G., & Cryan, J. F. (2011) · Pharmacological Reviews · doi:10.1124/pr.110.004036 · Cited by 184
Practical Strategies and Concepts in GPCR Allosteric Modulator Discovery: Recent Advances with Metabotropic Glutamate Receptors
Lindsley, C. W., Emmitte, K. A., Hopkins, C. R., Bridges, T. M., Gregory, K. J., Niswender, C. M., & Conn, P. J. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00656 · Cited by 184
Self-citation
ASD: a comprehensive database of allosteric proteins and modulators
Huang, Z., Zhu, L., Cao, Y., Wu, G. G., Liu, X., Chen, Y., Wang, Q., Shi, T., Zhao, Y., Wang, Y., et al. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq1022 · Cited by 177
An allosteric modulator to control endogenous G protein-coupled receptors with light
Pittolo, S., Gómez‐Santacana, X., Eckelt, K., Rovira, X., Dalton, J. A. R., Goudet, C., Pin, J., Llobet, A., Giraldo, J., Llebaria, A., et al. (2014) · Nature Chemical Biology · doi:10.1038/nchembio.1612 · Cited by 184
Discovery of Novel Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5 Reveals Chemical and Functional Diversity and In Vivo Activity in Rat Behavioral Models of Anxiolytic and Antipsychotic Activity
Rodriguez, A. L., Grier, M. D., Jones, C. K., Herman, E. J., Kane, A. S., Smith, R. L., Williams, R. D., Zhou, Y., Marlo, J. E., Days, E., et al. (2010) · Molecular Pharmacology · doi:10.1124/mol.110.067207 · Cited by 178
Self-citation
Advancing Biological Understanding and Therapeutics Discovery with Small-Molecule Probes
Schreiber, S. L., Kotz, J., Li, M., Aubé, J., Austin, C. P., Reed, J. C., Rosen, H., White, E. L., Sklar, L. A., Lindsley, C. W., et al. (2015) · Cell · doi:10.1016/j.cell.2015.05.023 · Cited by 173
Self-citation
The Best of Both Worlds? Bitopic Orthosteric/Allosteric Ligands of G Protein–Coupled Receptors
Valant, C., Lane, J. R., Sexton, P. M., & Christopoulos, A. (2011) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010611-134514 · Cited by 174
Self-citation
Molecular Mechanisms of Action and In Vivo Validation of an M4 Muscarinic Acetylcholine Receptor Allosteric Modulator with Potential Antipsychotic Properties
Leach, K., Loiacono, R. E., Felder, C. C., McKinzie, D. L., Mogg, A. J., Shaw, D. B., Sexton, P. M., & Christopoulos, A. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2009.194 · Cited by 167
Self-citation
The chemistry and biological activity of heterocycle-fused quinolinone derivatives: A review
Shiro, T., Fukaya, T., & Tobe, M. (2014) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2014.12.004 · Cited by 167
Computational design of peptide ligands
Vanhee, P., van der Sloot, A. M., Verschueren, E., Serrano, L. G., Rousseau, F., & Schymkowitz, J. W. H. (2011) · Trends in biotechnology · doi:10.1016/j.tibtech.2011.01.004 · Cited by 170
Cannabinoid receptors: nomenclature and pharmacological principles
Console‐Bram, L., Marcu, J. P., & Abood, M. E. (2012) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2012.02.009 · Cited by 169
Structure-Based Virtual Screening for Ligands of G Protein–Coupled Receptors: What Can Molecular Docking Do for You?
Ballante, F., Kooistra, A. J., Kampen, S., de Graaf, C., & Carlsson, J. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000246 · Cited by 169
Two Distinct Determinants of Ligand Specificity in T1R1/T1R3 (the Umami Taste Receptor)
Toda, Y., Nakagita, T., Hayakawa, T., Okada, S., Narukawa, M., Imai, H., Ishimaru, Y., & Misaka, T. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.494443 · Cited by 159
Allosteric Modulation of Class A GPCRs: Targets, Agents, and Emerging Concepts
Wold, E. A., Chen, J., Cunningham, K. A., & Zhou, J. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00875 · Cited by 161
Kappa-opioid ligands in the study and treatment of mood disorders
Carlezon, W. A., Béguin, C., Knoll, A. T., & Cohen, B. M. (2009) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2009.05.008 · Cited by 156
The properties of thermostabilised G protein-coupled receptors (StaRs) and their use in drug discovery
Robertson, N. J., Jazayeri, A., Errey, J. C., Baig, A. H., Hurrell, E., Zhukov, A., Langmead, C. J., Weir, M., & Marshall, F. H. (2010) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.07.001 · Cited by 163
Focusing on Adenosine Receptors as a Potential Targeted Therapy in Human Diseases
Effendi, W. I., Nagano, T., Kobayashi, K., & Nishimura, Y. (2020) · Cells · doi:10.3390/cells9030785 · Cited by 162
Metabotropic glutamate receptor-4 modulates adaptive immunity and restrains neuroinflammation
Fallarino, F., Volpi, C., Fazio, F., Notartomaso, S., Vacca, C., Busceti, C. L., Bicciato, S., Battaglia, G., Bruno, V., Puccetti, P., et al. (2010) · Nature Medicine · doi:10.1038/nm.2183 · Cited by 159
Pathway and Mechanism of Drug Binding to G-Protein-Coupled Receptors
Dror, R. O., Pan, A. C., Arlow, D. H., Borhani, D. W., Maragakis, P., Shan, Y., Xu, H., & Shaw, D. E. (2012) · Biophysical Journal · doi:10.1016/j.bpj.2011.11.2241 · Cited by 155
Exploring the role of receptor flexibility in structure-based drug discovery
Feixas, F., Lindert, S., Sinko, W., & McCammon, J. A. (2014) · Biophysical Chemistry · doi:10.1016/j.bpc.2013.10.007 · Cited by 156
“Molecular Switches” on mGluR Allosteric Ligands That Modulate Modes of Pharmacology
Wood, M. R., Hopkins, C. R., Brogan, J. T., Conn, P. J., & Lindsley, C. W. (2011) · Biochemistry · doi:10.1021/bi200129s · Cited by 157
Self-citation
Label-free whole-cell assays: expanding the scope of GPCR screening
Scott, C. W., & Peters, M. F. (2010) · Drug Discovery Today · doi:10.1016/j.drudis.2010.06.008 · Cited by 151
Probenecid Inhibits the Human Bitter Taste Receptor TAS2R16 and Suppresses Bitter Perception of Salicin
Greene, T. A., Alarcon, S., Thomas, A. A., Berdougo, E., Doranz, B. J., Breslin, P. A. S., & Rucker, J. B. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020123 · Cited by 147
Harnessing Allostery: A Novel Approach to Drug Discovery
Lu, S., Li, S., & Zhang, J. (2014) · Medicinal Research Reviews · doi:10.1002/med.21317 · Cited by 148
M1 muscarinic acetylcholine receptor in Alzheimer’s disease
Jiang, S., Li, Y., Zhang, C., Zhao, Y., Bu, G., Xu, H., & Zhang, Y. (2014) · Neuroscience Bulletin · doi:10.1007/s12264-013-1406-z · Cited by 147
Discovery and Characterization of Novel Allosteric Potentiators of M1 Muscarinic Receptors Reveals Multiple Modes of Activity
Marlo, J. E., Niswender, C. M., Days, E., Bridges, T. M., Xiang, Y., Rodriguez, A. L., Shirey-Rice, J. K., Brady, A. E., Nalywajko, T., Luo, Q., et al. (2008) · Molecular Pharmacology · doi:10.1124/mol.108.052886 · Cited by 147
Self-citation
Inhibition of Tumor Angiogenesis and Growth by a Small-Molecule Multi-FGF Receptor Blocker with Allosteric Properties
Bono, F., Smet, F. D., Herbert, C., Bock, K. D., Γεωργιάδου, Μ., Fons, P., Tjwa, M., Alcouffe, C., Ny, A., Bianciotto, M., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.02.019 · Cited by 146
Self-citation
Muscarinic Acetylcholine Receptor Agonists as Novel Treatments for Schizophrenia
Paul, S. M., Yohn, S. E., Popiolek, M., Miller, A., & Felder, C. C. (2022) · American Journal of Psychiatry · doi:10.1176/appi.ajp.21101083 · Cited by 152
Biased Ligands for Better Cardiovascular Drugs
DeWire, S. M., & Violin, J. D. (2011) · Circulation Research · doi:10.1161/circresaha.110.231308 · Cited by 145
Endogenous Allosteric Modulators of G Protein–Coupled Receptors
van der Westhuizen, E. T., Valant, C., Sexton, P. M., & Christopoulos, A. (2015) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.114.221606 · Cited by 145
Self-citation
Small Molecule Allosteric Modulators of G-Protein-Coupled Receptors: Drug–Target Interactions
Lu, S., & Zhang, J. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b01844 · Cited by 147
Allo-network drugs: harnessing allostery in cellular networks
Nussinov, R., Tsai, C., & Csermely, P. (2011) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2011.08.004 · Cited by 144
Accelerated molecular dynamics simulations of ligand binding to a muscarinic G-protein-coupled receptor
Kappel, K., Miao, Y., & McCammon, J. A. (2015) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583515000153 · Cited by 142
Regulation of β2-Adrenergic Receptor Function by Conformationally Selective Single-Domain Intrabodies
Staus, D. P., Wingler, L. M., Strachan, R. T., Rasmussen, S. G. F., Pardon, E., Ahn, S., Steyaert, J., Kobilka, B. K., & Lefkowitz, R. J. (2013) · Molecular Pharmacology · doi:10.1124/mol.113.089516 · Cited by 145
Allosteric Modulator ORG27569 Induces CB1 Cannabinoid Receptor High Affinity Agonist Binding State, Receptor Internalization, and Gi Protein-independent ERK1/2 Kinase Activation
Ahn, K. H., Mahmoud, M. M., & Kendall, D. A. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.316463 · Cited by 149
The Role of a Sodium Ion Binding Site in the Allosteric Modulation of the A2A Adenosine G Protein-Coupled Receptor
Gutiérrez‐de‐Terán, H., Massink, A., Rodriguez, D. J., Liu, W., Han, G. W., Joseph, J. S., Katritch, I., Heitman, L. H., Xia, L., IJzerman, A. P., et al. (2013) · Structure · doi:10.1016/j.str.2013.09.020 · Cited by 139
Muscarinic receptor subtype distribution in the central nervous system and relevance to aging and Alzheimer's disease
Lebois, E. P., Thorn, C. A., Edgerton, J. R., Popiolek, M., & Xi, S. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.11.018 · Cited by 145
Norbin Is an Endogenous Regulator of Metabotropic Glutamate Receptor 5 Signaling
Wang, H., Westin, L., Nong, Y., Birnbaum, S. G., Bendor, J., Brismar, H., Nestler, E. J., Aperia, A. C., Flajolet, M., & Greengard, P. (2009) · Science · doi:10.1126/science.1178496 · Cited by 140
The Different Ways through Which Specificity Works in Orthosteric and Allosteric Drugs
Nussinov, R., & Tsai, C. (2012) · Current Pharmaceutical Design · doi:10.2174/138161212799436377 · Cited by 149
Positive allosteric modulators of the human sweet taste receptor enhance sweet taste
Servant, G., Tachdjian, C., Tang, X.-Q., Werner, S., Zhang, F., Li, X., Kamdar, P., Petrovic, G., Ditschun, T. L., Java, A., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911670107 · Cited by 139

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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

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

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks