ArticleACS chemical biology2008
Ligand-binding pocket shape differences between sphingosine 1-phosphate (S1P) receptors S1P1 and S1P3 determine efficiency of chemical probe identification by ultrahigh-throughput screening.
Article in ACS chemical biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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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.
The trial behind it
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
25 citing papers in PubMed, 51 citations in OpenAlex.
- Drug Repurposing for Identification of S1P1 Agonists with Potential Application in Multiple Sclerosis Using In Silico Drug Design Approaches.Advanced pharmaceutical bulletin · 2023Article
- Article
- Alignment independent 3D-QSAR studies and molecular dynamics simulations for the identification of potent and selective S1PJournal of molecular graphics & modelling · 2020Article
- Article
- Article
- The novel sphingosine-1-phosphate receptors antagonist AD2900 affects lymphocyte activation and inhibits T-cell entry into the lymph nodes.Oncotarget · 2017Article
- A promising carbon-11-labeled sphingosine-1-phosphate receptor 1-specific PET tracer for imaging vascular injury.Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology · 2017Article
- Design, Synthesis, and In Vitro and In Vivo Evaluation of an (18)F-Labeled Sphingosine 1-Phosphate Receptor 1 (S1P1) PET Tracer.Journal of medicinal chemistry · 2016Article
- Bitopic Sphingosine 1-Phosphate Receptor 3 (S1P3) Antagonist Rescue from Complete Heart Block: Pharmacological and Genetic Evidence for Direct S1P3 Regulation of Mouse Cardiac Conduction.Molecular pharmacology · 2016Article
- Chemical and genetic tools to explore S1P biology.Current topics in microbiology and immunology · 2014Review
- Discovery, design and synthesis of a selective S1P(3) receptor allosteric agonist.Bioorganic & medicinal chemistry letters · 2013Article
- A sphingosine 1-phosphate receptor 2 selective allosteric agonist.Bioorganic & medicinal chemistry · 2013Article
- Innovation in academic chemical screening: filling the gaps in chemical biology.Current opinion in chemical biology · 2013Review
- Dissecting influenza virus pathogenesis uncovers a novel chemical approach to combat the infection.Virology · 2013Review
- Integrating the puzzle pieces: the current atomistic picture of phospholipid-G protein coupled receptor interactions.Biochimica et biophysica acta · 2013Review
- Novel selective allosteric and bitopic ligands for the S1P(3) receptor.ACS chemical biology · 2012Article
- Crystal structure of a lipid G protein-coupled receptor.Science (New York, N.Y.) · 2012Article
- Academic cross-fertilization by public screening yields a remarkable class of protein phosphatase methylesterase-1 inhibitors.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Article
- Pharmacological tools for lysophospholipid GPCRs: development of agonists and antagonists for LPA and S1P receptors.Acta pharmacologica Sinica · 2010Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
We have studied the sphingosine 1-phosphate (S1P) receptor system to better understand why certain molecular targets within a closely related family are much more tractable when identifying compelling chemical leads. Five medically important G-protein-coupled receptors for S1P regulate heart rate, coronary artery caliber, endothelial barrier integrity, and lymphocyte trafficking. Selective S1P receptor agonist probes would be of great utility to study receptor subtype-specific function. Through systematic screening of the same libraries, we identified novel selective agonist chemotypes for each of the S1P1 and S1P3 receptors. Ultrahigh-throughput screening (uHTS) for S1P1 was more effective than that for S1P3, with many selective, low nanomolar hits of proven mechanism emerging. Receptor structure modeling and ligand docking reveal differences between the receptor binding pockets, which are the basis for subtype selectivity. Novel selective agonists interact primarily in the hydrophobic pocket of the receptor in the absence of headgroup interactions. Chemistry-space and shape-based analysis of the screening libraries in combination with the binding models explain the observed differential hit rates and enhanced efficiency for lead discovery for S1P1 versus S1P3 in this closely related receptor family.
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What OpenQuestion holds
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.