ArticleProceedings of the National Academy of Sciences of the United States of America2009
Design and x-ray crystal structures of high-potency nonsteroidal glucocorticoid agonists exploiting a novel binding site on the receptor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 72 citations in OpenAlex.
- The multimerization pathway of the glucocorticoid receptor.Nucleic acids research · 2025Article
- Evaluation of the Safety and Antiproliferative Activity of Bulgarian Rose Essential Oil: An In Vitro and In Silico Model of Colorectal Adenocarcinoma.Current issues in molecular biology · 2025Article
- Bile acids target an exposed cavity in the glucocorticoid receptor modulating receptor self-assembly, chromatin binding and transcriptional activity.bioRxiv : the preprint server for biology · 2025Article
- HIt Discovery using docking ENriched by GEnerative Modeling (HIDDEN GEM): A novel computational workflow for accelerated virtual screening of ultra-large chemical libraries.Molecular informatics · 2024Article
- Review
- The multivalency of the glucocorticoid receptor ligand-binding domain explains its manifold physiological activities.Nucleic acids research · 2022Article
- Dimerization of the Glucocorticoid Receptor and Its Importance in (Patho)physiology: A Primer.Cells · 2022Review
- Development of highly potent glucocorticoids for steroid-resistant severe asthma.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- GR Dimerization and the Impact of GR Dimerization on GR Protein Stability and Half-Life.Frontiers in immunology · 2019Review
- An Approach to Greater Specificity for Glucocorticoids.Frontiers in endocrinology · 2018Review
- Workflows and performances in the ranking prediction of 2016 D3R Grand Challenge 2: lessons learned from a collaborative effort.Journal of computer-aided molecular design · 2018Article
- Selective Glucocorticoid Receptor Properties of GSK866 Analogs with Cysteine Reactive Warheads.Frontiers in immunology · 2017Article
- Understanding how long-acting βBritish journal of pharmacology · 2016Review
- An analysis of glucocorticoid receptor-mediated gene expression in BEAS-2B human airway epithelial cells identifies distinct, ligand-directed, transcription profiles with implications for asthma therapeutics.British journal of pharmacology · 2015Article
- Article
- Research resource: modulators of glucocorticoid receptor activity identified by a new high-throughput screening assay.Molecular endocrinology (Baltimore, Md.) · 2014Article
- Discovery of GW870086: a potent anti-inflammatory steroid with a unique pharmacological profile.British journal of pharmacology · 2013Article
- The road less traveled: new views of steroid receptor action from the path of dose-response curves.Molecular and cellular endocrinology · 2012Review
- Collective dynamics differentiates functional divergence in protein evolution.PLoS computational biology · 2012Article
- Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Crystallography and computer modeling have been used to exploit a previously unexplored channel in the glucocorticoid receptor (GR). Highly potent, nonsteroidal indazole amides showing excellent complementarity to the channel were designed with the assistance of the computational technique AlleGrow. The accuracy of the design process was demonstrated through crystallographic structural determination of the GR ligand-binding domain-agonist complex of the D-prolinamide derivative 11. The utility of the channel was further exemplified through the design of a potent phenylindazole in which structural motifs, seen to interact with the traditional GR ligand pocket, were abandoned and replaced by interactions within the new channel. Occupation of the channel was confirmed with a second GR crystal structure of this truncated D-alaninamide derivative 13. Compound 11 displays properties compatible with development as an intranasal solution formulation, whereas oral bioavailability has been demonstrated with a related truncated exemplar 14. Data with the pyrrolidinone amide 12 demonstrate the potential for further elaboration within the "meta" channel to deliver compounds with selectivity for the desired transrepressive activity of glucocorticoids. The discovery of these interactions with this important receptor offers significant opportunities for the design of novel GR modulators.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.