ArticleACS chemical biology2012
Novel selective allosteric and bitopic ligands for the S1P(3) receptor.
Article in ACS chemical biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 59 citations in OpenAlex.
- Endothelial S1PR3 downregulation exacerbates pressure overload-induced cardiac remodeling by promoting fibrosis and inflammation.Science China. Life sciences · 2026Article
- Structural basis of allosteric and bitopic ligands binding in sphingosine-1-phosphate receptors 2 and 3.Protein & cell · 2026Article
- Sphingosine-1-phosphate receptor signaling regulates an ERK1/2-p65 molecular switch in macrophages duringFrontiers in pharmacology · 2026Article
- Article
- Sphingosine kinase 1/S1P receptor signaling axis is essential for cellular uptake of Neisseria meningitidis in brain endothelial cells.PLoS pathogens · 2023Article
- The role of sphingosine-1-phosphate in the development and progression of Parkinson's disease.Frontiers in cellular neuroscience · 2023Review
- Sphingosine 1-Phoshpate Receptors are Located in Synapses and Control Spontaneous Activity of Mouse Neurons in Culture.Neurochemical research · 2022Article
- Modulation of Specific Sphingosine-1-Phosphate Receptors Augments a Repair Mediating Schwann Cell Phenotype.International journal of molecular sciences · 2022Article
- Structural insights into sphingosine-1-phosphate recognition and ligand selectivity of S1PR3-Gi signaling complexes.Cell research · 2022Article
- Sphingosine-1-phosphate modulates PAR1-mediated human platelet activation in a concentration-dependent biphasic manner.Scientific reports · 2021Article
- S1P lyase inhibition protects against sepsis by promoting disease tolerance via the S1P/S1PR3 axis.EBioMedicine · 2020Observational
- 2016 Philip S. Portoghese Medicinal Chemistry Lectureship: Designing Bivalent or Bitopic Molecules for G-Protein Coupled Receptors. The Whole Is Greater Than the Sum of Its Parts.Journal of medicinal chemistry · 2020Article
- Enhanced expression of the sphingosine-1-phosphate-receptor-3 causes acute myelogenous leukemia in mice.Leukemia · 2020Article
- Utilization of Biased G Protein-Coupled ReceptorSignaling towards Development of Safer andPersonalized Therapeutics.Molecules (Basel, Switzerland) · 2019Review
- Designing Hybrids Targeting the Cholinergic System by Modulating the Muscarinic and Nicotinic Receptors: A Concept to Treat Alzheimer's Disease.Molecules (Basel, Switzerland) · 2018Review
- Sphingosine-1-phosphate receptors and innate immunity.Cellular microbiology · 2018Review
- Sphingosine 1-phosphate (S1P) reduces hepatocyte growth factor-induced migration of hepatocellular carcinoma cells via S1P receptor 2.PloS one · 2018Article
- Sphingosine 1-phosphate receptor 3 and RhoA signaling mediate inflammatory gene expression in astrocytes.Journal of neuroinflammation · 2017Article
- Selective coupling of the S1PJournal of molecular and cellular cardiology · 2017Article
- 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
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Sphingosine 1-phosphate (S1P) is a lysophospholipid signaling molecule that regulates important biological functions, including lymphocyte trafficking and vascular development, by activating G protein-coupled receptors for S1P, namely, S1P(1) through S1P(5). Here, we map the S1P(3) binding pocket with a novel allosteric agonist (CYM-5541), an orthosteric agonist (S1P), and a novel bitopic antagonist (SPM-242). With a combination of site-directed mutagenesis, ligand competition assay, and molecular modeling, we concluded that S1P and CYM-5541 occupy different chemical spaces in the ligand binding pocket of S1P(3). CYM-5541 allowed us to identify an allosteric site where Phe263 is a key gate-keeper residue for its affinity and efficacy. This ligand lacks a polar moiety, and the novel allosteric hydrophobic pocket permits S1P(3) selectivity of CYM-5541 within the highly similar S1P receptor family. However, a novel S1P(3)-selective antagonist, SPM-242, in the S1P(3) pocket occupies the ligand binding spaces of both S1P and CYM-5541, showing its bitopic mode of binding. Therefore, our coordinated approach with biochemical data and molecular modeling, based on our recently published S1P(1) crystal structure data in a highly conserved set of related receptors with a shared ligand, provides a strong basis for the successful optimization of orthosteric, allosteric, and bitopic modulators of S1P(3).
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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.