The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Structure-based discovery of β 2 -adrenergic receptor ligands
Open accessAbstract
Aminergic G protein-coupled receptors (GPCRs) have been a major focus of pharmaceutical research for many years. Due partly to the lack of reliable receptor structures, drug discovery efforts have been largely ligand-based. The recently determined X-ray structure of the β 2 -adrenergic receptor offers an opportunity to investigate the advantages and limitations inherent in a structure-based approach to ligand discovery against this and related GPCR targets. Approximately 1 million commercially available, “lead-like” molecules were docked against the β 2 -adrenergic receptor structure. On testing of 25 high-ranking molecules, 6 were active with binding affinities <4 μM, with the best molecule binding with a K i of 9 nM (95% confidence interval 7–10 nM). Five of these molecules were inverse agonists. The high hit rate, the high affinity of the most potent molecule, the discovery of unprecedented chemotypes among the new inhibitors, and the apparent bias toward inverse agonists among the docking hits, have implications for structure-based approaches against GPCRs that recognize small organic molecules.
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
Development and validation of a genetic algorithm for flexible docking 1 1Edited by F. E. Cohen
Jones, G., Willett, P., Glen, R. C., Leach, A. R., & Taylor, R. (1997) · Journal of Molecular Biology · doi:10.1006/jmbi.1996.0897 · Cited by 6,763
ZINC − A Free Database of Commercially Available Compounds for Virtual Screening
Irwin, J. J., & Shoichet, B. K. (2005) · Journal of Chemical Information and Modeling · doi:10.1021/ci049714+ · Cited by 4,058
Self-citationDrugBank: a comprehensive resource for in silico drug discovery and exploration
Wishart, D. S. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkj067 · Cited by 3,892
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
Drugs for bad bugs: confronting the challenges of antibacterial discovery
Payne, D. J., Gwynn, M. N., Holmes, D. J., & Pompliano, D. L. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2201 · Cited by 2,512
A model binding site for testing scoring functions in molecular docking.
Wei, B. Q., Baase, W. A., Weaver, L. H., Matthews, B. W., & Shoichet, B. K. (2002) · Journal of Molecular Biology · doi:10.1016/s0022-2836(02)00777-5 · Cited by 237
Self-citation
Cited by
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
Self-citationDirectory of useful decoys, enhanced (DUD-E): better ligands and decoys for better benchmarking.
Mysinger, M. M., Carchia, M., Irwin, J. J., & Shoichet, B. K. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm300687e · Cited by 2,412
Structure of the human histamine H1 receptor complex with doxepin
Shimamura, T., Shiroishi, M., Weyand, S., Tsujimoto, H., Winter, G., Katritch, V., Abagyan, R., Cherezov, V., Liu, W., Han, G. W., et al. (2011) · Nature · doi:10.1038/nature10236 · Cited by 804
How Ligands Illuminate GPCR Molecular Pharmacology
Wacker, D., Stevens, R. C., & Roth, B. L. (2017) · Cell · doi:10.1016/j.cell.2017.07.009 · Cited by 560
A practical guide to large-scale docking
Bender, B. J., Gahbauer, S., Luttens, A., Lyu, J., Webb, C. M., Stein, R. M., Fink, E. A., Balius, T. E., Carlsson, J., Irwin, J. J., et al. (2021) · Nature Protocols · doi:10.1038/s41596-021-00597-z · Cited by 546
“In contrast, the pose of an inverse agonist also identi fi ed at the β 2 adrenergic receptor from in silico docking 39 was con fi rmed by X-ray crystal-lography 107 , demonstrating the variability in outcomes even at the same target.”
BackgroundSelf-citation
Metadata
- Authors
- Kolb, P., Rosenbaum, D. M., Irwin, J. J., Fung, J. J., Kobilka, B. K., & Shoichet, B. K.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2009-04-21
- Volume
- 106
- Issue
- 16
- Pages
- 6843-6848
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2168833646
- Cited by
- 288
- References
- 6
- FWCI
- 31.55
- 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: Structure-based discovery of β 2 -adrenergic receptor ligands. https://app.cochat.ai/papers/10.1073/pnas.0812657106
- The paper
- Kolb, P., Rosenbaum, D. M., Irwin, J. J., Fung, J. J., Kobilka, B. K., & Shoichet, B. K. (2009). Structure-based discovery of β 2 -adrenergic receptor ligands. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0812657106
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.
