{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Fritzemeier R"],"funding":["National Institute of Allergy and Infectious Diseases","NIAID NIH HHS"],"pagination":["7656-7681"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9733493"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["65(11)"],"pubmed_abstract":["Sphingosine 1-phosphate (S1P) is a pleiotropic signaling molecule that interacts with five G-protein-coupled receptors (S1P1-5) to regulate cellular signaling pathways. S1P export is facilitated by Mfsd2b and spinster homologue 2 (Spns2). While mouse genetic studies suggest that Spns2 functions to maintain lymph S1P, Spns2 inhibitors are necessary to understand its biology and to learn whether Spns2 is a viable drug target. Herein, we report a structure-activity relationship study that identified the first Spns2 inhibitor <b>16d</b> (SLF1081851). In vitro studies in HeLa cells demonstrated that <b>16d</b> inhibited S1P release with an IC<sub>50</sub> of 1.93 μM. Administration of <b>16d</b> to mice and rats drove significant decreases in circulating lymphocyte counts and plasma S1P concent"],"journal":["Journal of medicinal chemistry"],"pubmed_title":["Discovery of In Vivo Active Sphingosine-1-phosphate Transporter (Spns2) Inhibitors."],"pmcid":["PMC9733493"],"funding_grant_id":["R01 AI144026"],"pubmed_authors":["Fritzemeier R","Kharel Y","Lynch KR","Huang T","Peralta A","Payette M","Foster D","Santos WL"],"additional_accession":[]},"is_claimable":false,"name":"Discovery of In Vivo Active Sphingosine-1-phosphate Transporter (Spns2) Inhibitors.","description":"Sphingosine 1-phosphate (S1P) is a pleiotropic signaling molecule that interacts with five G-protein-coupled receptors (S1P1-5) to regulate cellular signaling pathways. S1P export is facilitated by Mfsd2b and spinster homologue 2 (Spns2). While mouse genetic studies suggest that Spns2 functions to maintain lymph S1P, Spns2 inhibitors are necessary to understand its biology and to learn whether Spns2 is a viable drug target. Herein, we report a structure-activity relationship study that identified the first Spns2 inhibitor <b>16d</b> (SLF1081851). In vitro studies in HeLa cells demonstrated that <b>16d</b> inhibited S1P release with an IC<sub>50</sub> of 1.93 μM. Administration of <b>16d</b> to mice and rats drove significant decreases in circulating lymphocyte counts and plasma S1P concent","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jun","modification":"2025-04-18T23:25:04.356Z","creation":"2025-04-07T10:59:04.717Z"},"accession":"S-EPMC9733493","cross_references":{"pubmed":["35609189"],"doi":["10.1021/acs.jmedchem.1c02171"]}}