The DOI matches its Crossref record; 144 of the 145 references it cites were found in a registry or an index.
Strategies to Discover Unexpected Targets for Drugs Active at G Protein–Coupled Receptors
Abstract
G protein–coupled receptors (GPCRs) are an evolutionarily conserved family of signaling molecules comprising approximately 2% of the human genome; this receptor family remains a central focus in basic pharmacology studies and drug discovery efforts. Detailed studies of drug action at GPCRs over the past decade have revealed existing and novel ligands that exhibit polypharmacology—that is, drugs with activity at more than one receptor target for which they were designed. These “off-target” drug actions can be a liability that causes adverse side effects; however, in several cases, drugs with less selectivity demonstrate better clinical efficacy. Here we review physical screening and cheminformatic approaches that define drug activity at the GPCR receptorome. In many cases, such profiling has revealed unexpected targets that explain therapeutic actions as well as off-targets underlying drug side effects. Such drug-receptor profiling has also provided new insights into mechanisms of action of existing drugs and has suggested directions for future drug development.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“most clinically effective antipsychotics also exhibit a myriad of other actions that contribute to both therapeutic and side-effect profiles [359,360].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [359]
Citations
Cites
The sequence of the human genome
Venter, J. C., Adams, M. D., Myers, E. W., Li, P. W., Mural, R. J., Sutton, G. G., Smith, H. O., Yandell, M., Evans, C. A., Holt, R. A., et al. (2001) · Science · doi:10.1126/science.1058040 · Cited by 13,909
Massagué, J. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.753 · Cited by 7,571
Crystal Structure of Rhodopsin: A G Protein-Coupled Receptor
Palczewski, K., Kumasaka, T., Hori, T., Behnke, C. A., Motoshima, H., Fox, B. A., Trong, I. L., Teller, D. C., Okada, T., Stenkamp, R. E., et al. (2000) · Science · doi:10.1126/science.289.5480.739 · Cited by 5,637
Common polygenic variation contributes to risk of schizophrenia and bipolar disorder
The International Schizophrenia Consortium (2009) · Nature · doi:10.1038/nature08185 · Cited by 4,821
Network pharmacology: the next paradigm in drug discovery
Hopkins, A. L. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.118 · Cited by 4,622
Clozapine for the Treatment-Resistant Schizophrenic: A Double-blind Comparison With Chlorpromazine
Kane, J. (1988) · Archives of General Psychiatry · doi:10.1001/archpsyc.1988.01800330013001 · Cited by 4,156
Hopkins, A. L., & Groom, C. R. (2002) · Nature Reviews Drug Discovery · doi:10.1038/nrd892 · Cited by 3,305
High-Resolution Crystal Structure of an Engineered Human β 2 -Adrenergic G Protein–Coupled Receptor
Cherezov, V., Rosenbaum, D. M., Hanson, M. A., Rasmussen, S. G. F., Thian, F. S., Kobilka, T. S., Choi, H., Kühn, P., Weis, W. I., Kobilka, B. K., et al. (2007) · Science · doi:10.1126/science.1150577 · Cited by 3,280
Fredriksson, R., Lagerström, M. C., Lundin, L.-G., & Schiöth, H. B. (2003) · Molecular Pharmacology · doi:10.1124/mol.63.6.1256 · Cited by 2,941
Relating protein pharmacology by ligand chemistry
Keiser, M. J., Roth, B. L., Armbruster, B. N., Ernsberger, P., Irwin, J. J., & Shoichet, B. K. (2007) · Nature Biotechnology · doi:10.1038/nbt1284 · Cited by 2,402
Self-citation
Research works printed but not linked: 4
- Alouani S, 2000, Methods Mol. Biol., 138, 135
- Stewart GD, 2010, Am. Chem. Soc. Chem. Biol., 5, 365
- Ozawa A, 2010, Am. Assoc. Pharm. Sci. J., 12, 378
- Hippius H., 1999, J. Clin. Psychiatry, 60, 22
Cited by
Sorted by citations
Roth, B. L. (2016) · Neuron · doi:10.1016/j.neuron.2016.01.040 · Cited by 1,742
Self-citationG Protein-Coupled Receptors as Targets for Approved Drugs: How Many Targets and How Many Drugs?
Sriram, K., & Insel, P. A. (2018) · Molecular Pharmacology · doi:10.1124/mol.117.111062 · Cited by 1,258
Structure-Function of the G Protein–Coupled Receptor Superfamily
Katritch, V., Cherezov, V., & Stevens, R. C. (2012) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-032112-135923 · Cited by 1,096
PRESTO-Tango as an open-source resource for interrogation of the druggable human GPCRome
Kroeze, W. K., Sassano, M. F., Huang, X.-P., Lansu, K., McCorvy, J. D., Giguère, P. M., Sciaky, N., & Roth, B. L. (2015) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3014 · Cited by 755
Self-citationStructural Features for Functional Selectivity at Serotonin Receptors
Wacker, D., Wang, C., Katritch, V., Han, G. W., Huang, X., Vardy, E., McCorvy, J. D., Jiang, Y., Chu, M., Siu, F., et al. (2013) · Science · doi:10.1126/science.1232808 · Cited by 706
Self-citation
Metadata
- Authors
- Allen, J. A., & Roth, B. L.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Venue
- Annual Review of Pharmacology and Toxicology
- Publisher
- Annual Reviews
- Published
- 2011-02-10
- Volume
- 51
- Issue
- 1
- Pages
- 117-144
- ISSN
- 0362-1642 (ISSN-L)
- 1545-4304
- OpenAlex
- W2160203886
- Cited by
- 216
- References
- 145
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 16 · 2023: 12 · 2022: 15 · 2021: 7 · 2020: 10 · 2019: 15 · 2018: 15 · 2017: 14 · 2016: 10 · 2015: 22 · 2014: 21 · 2013: 22 · 2012: 17
- FWCI
- 1.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Annual Review of Pharmacology and Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- U.S. Public Health Service (HHSN-271-2008-00025-C)
- National Institute of Mental Health (U19MH082441, R01MH061887)
- National Institute on Drug Abuse (R01DA017204)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD040127)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Computational Drug Discovery Methods
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- G protein-coupled receptors, polypharmacology, cheminformatics, adverse drug reactions, receptor selectivity, mechanisms of drug action, drug development
- MeSH terms
- Animals, Pharmaceutical Preparations, Humans, Ligands, Drug Design, Drug Delivery Systems, Computational Biology, Receptors, G-Protein-Coupled, Drug Discovery, Drug-Related Side Effects and Adverse Reactions
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
