The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Practical Strategies and Concepts in GPCR Allosteric Modulator Discovery: Recent Advances with Metabotropic Glutamate Receptors
Open accessAbstract
Allosteric modulation of GPCRs has initiated a new era of basic and translational discovery, filled with therapeutic promise yet fraught with caveats. Allosteric ligands stabilize unique conformations of the GPCR that afford fundamentally new receptors, capable of novel pharmacology, unprecedented subtype selectivity, and unique signal bias. This review provides a comprehensive overview of the basics of GPCR allosteric pharmacology, medicinal chemistry, drug metabolism, and validated approaches to address each of the major challenges and caveats. Then, the review narrows focus to highlight recent advances in the discovery of allosteric ligands for metabotropic glutamate receptor subtypes 1-5 and 7 (mGlu1-5,7) highlighting key concepts ("molecular switches", signal bias, heterodimers) and practical solutions to enable the development of tool compounds and clinical candidates. The review closes with a section on late-breaking new advances with allosteric ligands for other GPCRs and emerging data for endogenous allosteric modulators.
Overview
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
Cites
Statistics
Verification
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.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
How many drug targets are there?
Overington, J. P., Al-Lazikani, B., & Hopkins, A. L. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd2199 · Cited by 3,505
Lessons learned from the fate of AstraZeneca's drug pipeline: a five-dimensional framework
Cook, D., Brown, D., Alexander, R., March, R., Morgan, P., Satterthwaite, G., & Pangalos, M. N. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4309 · Cited by 1,344
Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders
Jeffrey Conn, P., Christopoulos, A., & Lindsley, C. W. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2760 · Cited by 1,063
Self-citationPatil, 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
Loss of bidirectional striatal synaptic plasticity in L-DOPA-induced dyskinesia
Picconi, B., Centonze, D., Håkansson, K., Bernardi, G., Greengard, P., Fisone, G., Cenci, M. A., & Calabresi, P. (2003) · Nature Neuroscience · doi:10.1038/nn1040 · Cited by 821
The Meta-Analyses of Glucose- and Insulin-related traits Consortium (MAGIC), Horikoshi, M., Early Growth Genetics (EGG) Consortium, Yaghootkar, H., Mook-Kanamori, D. O., Sovio, U., Taal, H. R., Hennig, B. J., Bradfield, J. P., St Pourcain, B., et al. (2013) · Nature Genetics · doi:10.1038/ng.2477 · Cited by 309
Kinon, B. J., Zhang, L., Millen, B. A., Osuntokun, O. O., Williams, J. E., Kollack-Walker, S., Jackson, K., Kryzhanovskaya, L., & Jarkova, N. (2011) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e318218dcd5 · Cited by 256
Chaki, S., Yoshikawa, R., Hirota, S., Shimazaki, T., Maeda, M., Kawashima, N., Yoshimizu, T., Yasuhara, A., Sakagami, K., Okuyama, S., et al. (2004) · Neuropharmacology · doi:10.1016/j.neuropharm.2003.10.009 · Cited by 254
Hay, D. L., Poyner, D. R., & Sexton, P. M. (2006) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2005.06.015 · Cited by 239
Koike, H., Iijima, M., & Chaki, S. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.08.034 · Cited by 114
Cited by
Free Fatty Acid Receptors in Health and Disease
Kimura, I., Ichimura, A., Ohue-Kitano, R., & Igarashi, M. (2020) · Physiological Reviews · doi:10.1152/physrev.00041.2018 · Cited by 1,018
G protein-coupled receptors: structure- and function-based drug discovery
Yang, D., Zhou, Q., Labroska, V., Qin, S., Darbalaei, S., Wu, Y., Yuliantie, E., Xie, L., Tao, H., Cheng, J., et al. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00435-w · Cited by 632
Terpenoids From Cannabis Do Not Mediate an Entourage Effect by Acting at Cannabinoid Receptors
Finlay, D. B., Sircombe, K. J., Nimick, M., Jones, C., & Glass, M. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00359 · Cited by 99
Hou, T., Bian, Y., McGuire, T., & Xie, X.-Q. (2021) · Biomolecules · doi:10.3390/biom11060870 · Cited by 30
Metadata
- Authors
- Lindsley, C. W., Emmitte, K. A., Hopkins, C. R., Bridges, T. M., Gregory, K. J., Niswender, C. M., & Conn, P. J.
- Venue
- Chemical Reviews
- Publisher
- American Chemical Society (ACS)
- Published
- 2016-02-16
- Volume
- 116
- Issue
- 11
- Pages
- 6707-6741
- ISSN
- 0009-2665 (ISSN-L)
- 1520-6890
- OpenAlex
- W2274383865
- Cited by
- 181
- References
- 12
- FWCI
- 2.10
- Type
- journal article
- Language
- en
- Open access
- green
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
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Practical Strategies and Concepts in GPCR Allosteric Modulator Discovery: Recent Advances with Metabotropic Glutamate Receptors. https://app.cochat.ai/papers/10.1021/acs.chemrev.5b00656
- The paper
- Lindsley, C. W., Emmitte, K. A., Hopkins, C. R., Bridges, T. M., Gregory, K. J., Niswender, C. M., & Conn, P. J. (2016). Practical Strategies and Concepts in GPCR Allosteric Modulator Discovery: Recent Advances with Metabotropic Glutamate Receptors. Chemical Reviews. https://doi.org/10.1021/acs.chemrev.5b00656
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
