{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:51:22Z","timestamp":1791474682909,"version":"4.3.4"},"reference-count":37,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T00:00:00Z","timestamp":1629763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["310030_135619"],"award-info":[{"award-number":["310030_135619"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008486","name":"Schweizerische Multiple Sklerose Gesellschaft","doi-asserted-by":"publisher","award":["n.a."],"award-info":[{"award-number":["n.a."]}],"id":[{"id":"10.13039\/501100008486","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GRK2158, INST 208\/690-1"],"award-info":[{"award-number":["GRK2158, INST 208\/690-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000921","name":"European Cooperation in Science and Technology","doi-asserted-by":"publisher","award":["CA15135, CA18133, CA18240"],"award-info":[{"award-number":["CA15135, CA18133, CA18240"]}],"id":[{"id":"10.13039\/501100000921","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hochschulstiftung der Universit\u00e4t Bern","award":["20\/2020"],"award-info":[{"award-number":["20\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Sphingosine 1-phosphate (S1P) is an extensively studied signaling molecule that contributes to cell proliferation, survival, migration and other functions through binding to specific S1P receptors. The cycle of S1P1 internalization upon S1P binding and recycling to the cell surface when local S1P concentrations are low drives T cell trafficking. S1P1 modulators, such as fingolimod, disrupt this recycling by inducing persistent S1P1 internalization and receptor degradation, which results in blocked egress of T cells from the secondary lymphoid tissues. The approval of these compounds for the treatment of multiple sclerosis has placed the development of S1PR modulators in the focus of pharmacological research, mostly for autoimmune indications. Here, we report on a novel anellated bismorpholino derivative of oxy-fingolimod, named ST-2191, which exerts selective S1P1 agonist and functional antagonist potency. ST-2191 is also effective in reducing the lymphocyte number in mice, and this effect is not dependent on phosphorylation by sphingosine kinase 2 for activity. These data show that ST-2191 is a novel S1P1 modulator, but further experiments are needed to analyze the therapeutic impact of ST-2191 in animal models of autoimmune diseases.<\/jats:p>","DOI":"10.3390\/molecules26175134","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T22:09:39Z","timestamp":1629842979000},"page":"5134","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["ST-2191, an Anellated Bismorpholino Derivative of Oxy-Fingolimod, Shows Selective S1P1 Agonist and Functional Antagonist Potency In Vitro and In Vivo"],"prefix":"10.3390","volume":"26","author":[{"given":"Bisera","family":"Stepanovska Tanturovska","sequence":"first","affiliation":[{"name":"Institute of Pharmacology, University of Bern, Inselspital INO-F, CH-3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Zivkovic","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University D\u00fcsseldorf, Universitaetsstr. 1, D-40225 Duesseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faik","family":"Imeri","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, University of Bern, Inselspital INO-F, CH-3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Homann","sequence":"additional","affiliation":[{"name":"Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert Allee 114\u2013116, D-14558 Nuthetal, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1888-9595","authenticated-orcid":false,"given":"Burkhard","family":"Kleuser","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy, Freie Universit\u00e4t Berlin, K\u00f6nigin-Luise-Str. 2+4, D-14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3336-1710","authenticated-orcid":false,"given":"Holger","family":"Stark","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University D\u00fcsseldorf, Universitaetsstr. 1, D-40225 Duesseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1615-5691","authenticated-orcid":false,"given":"Andrea","family":"Huwiler","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, University of Bern, Inselspital INO-F, CH-3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1194\/jlr.E400004-JLR200","article-title":"A comprehensive classification system for lipids","volume":"46","author":"Fahy","year":"2005","journal-title":"J. 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