ArticleBioorganic & medicinal chemistry2013
A sphingosine 1-phosphate receptor 2 selective allosteric agonist.
Article in Bioorganic & medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 65 citations in OpenAlex.
- Structural basis of allosteric and bitopic ligands binding in sphingosine-1-phosphate receptors 2 and 3.Protein & cell · 2026Article
- Tuning the Response of GPCR-Based Yeast Sensors Using Fluorescent Reporters.ACS synthetic biology · 2026Article
- Article
- Sphingosine-1-phosphate receptor signaling regulates an ERK1/2-p65 molecular switch in macrophages duringFrontiers in pharmacology · 2026Article
- Biological Actions of Bile Acids via Cell Surface Receptors.International journal of molecular sciences · 2025Review
- Spinster homolog 2/S1P signaling ameliorates macrophage inflammatory response to bacterial infections by balancing PGECell communication and signaling : CCS · 2024Article
- The Current Landscape in the Development of Small-molecule Modulators Targeting Sphingosine-1-phosphate Receptors to Treat Neurodegenerative Diseases.Current topics in medicinal chemistry · 2024Review
- Structure, function and drug discovery of GPCR signaling.Molecular biomedicine · 2023Review
- Sphingosine kinase 1/S1P receptor signaling axis is essential for cellular uptake of Neisseria meningitidis in brain endothelial cells.PLoS pathogens · 2023Article
- Chronic Glucocorticoid Exposure Induced an S1PR2-RORγ Axis to Enhance Hepatic Gluconeogenesis in Male Mice.Diabetes · 2023Article
- Sphingosine 1-Phoshpate Receptors are Located in Synapses and Control Spontaneous Activity of Mouse Neurons in Culture.Neurochemical research · 2022Article
- Slit-Robo signalling establishes a Sphingosine-1-phosphate gradient to polarise fin mesenchyme.EMBO reports · 2022Article
- Sphingosine-1-phosphate modulates PAR1-mediated human platelet activation in a concentration-dependent biphasic manner.Scientific reports · 2021Article
- Metabolic tuning of inhibition regulates hippocampal neurogenesis in the adult brain.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Activation of sphingosine 1-phosphate receptor 2 attenuates chemotherapy-induced neuropathy.The Journal of biological chemistry · 2020Article
- Design, synthesis, and in vitro bioactivity evaluation of fluorine-containing analogues for sphingosine-1-phosphate 2 receptor.Bioorganic & medicinal chemistry · 2019Article
- Survival benefit of sphingosin-1-phosphate and receptors expressions in breast cancer patients.Cancer medicine · 2018Article
- Article
- Structural centrosome aberrations sensitize polarized epithelia to basal cell extrusion.Open biology · 2018Article
- Design and synthesis of pyrazolopyridine derivatives as sphingosine 1-phosphate receptor 2 ligands.Bioorganic & medicinal chemistry letters · 2018Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Molecular probe tool compounds for the Sphingosine 1-phosphate receptor 2 (S1PR2) are important for investigating the multiple biological processes in which the S1PR2 receptor has been implicated. Amongst these are NF-κB-mediated tumor cell survival and fibroblast chemotaxis to fibronectin. Here we report our efforts to identify selective chemical probes for S1PR2 and their characterization. We employed high throughput screening to identify two compounds which activate the S1PR2 receptor. SAR optimization led to compounds with high nanomolar potency. These compounds, XAX-162 and CYM-5520, are highly selective and do not activate other S1P receptors. Binding of CYM-5520 is not competitive with the antagonist JTE-013. Mutation of receptor residues responsible for binding to the zwitterionic headgroup of sphingosine 1-phosphate (S1P) abolishes S1P activation of the receptor, but not activation by CYM-5520. Competitive binding experiments with radiolabeled S1P demonstrate that CYM-5520 is an allosteric agonist and does not displace the native ligand. Computational modeling suggests that CYM-5520 binds lower in the orthosteric binding pocket, and that co-binding with S1P is energetically well tolerated. In summary, we have identified an allosteric S1PR2 selective agonist compound.
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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.