{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T14:32:41Z","timestamp":1787668361546,"version":"build-2736575974"},"reference-count":73,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"crossref","award":["2024M763206"],"award-info":[{"award-number":["2024M763206"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004479","name":"Jiangxi Provincial Natural Science Foundation","doi-asserted-by":"crossref","award":["20232BAB216133"],"award-info":[{"award-number":["20232BAB216133"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004479","name":"Jiangxi Provincial Natural Science Foundation","doi-asserted-by":"crossref","award":["20232BAB206179"],"award-info":[{"award-number":["20232BAB206179"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004479","name":"Jiangxi Provincial Natural Science Foundation","doi-asserted-by":"crossref","award":["20232BAB216123"],"award-info":[{"award-number":["20232BAB216123"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Dalian Institute of Chemical Physics, Chinese Academy of Sciences and the Second Hospital of Dalian Medical University","award":["DMU-2&DICP UN202402"],"award-info":[{"award-number":["DMU-2&DICP UN202402"]}]},{"name":"Guidance Project on Dalian Health and Wellness","award":["2024ZDJH01PT076"],"award-info":[{"award-number":["2024ZDJH01PT076"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Naunyn-Schmiedeberg's Arch Pharmacol"],"published-print":{"date-parts":[[2026,8]]},"DOI":"10.1007\/s00210-026-05504-5","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T03:02:59Z","timestamp":1780023779000},"page":"17807-17824","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Label-free cell phenotypic profiling of sphingosine-1-phosphate receptor 1 and discovery of its agonist from natural products"],"prefix":"10.1007","volume":"399","author":[{"given":"Xiyi","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongming","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomin","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lai","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jixia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aoxue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"5504_CR1","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.copbio.2004.09.003","volume":"15","author":"DD Baker","year":"2004","unstructured":"Baker DD, Alvi KA (2004) Small-molecule natural products: new structures, new activities. Curr Opin Biotechnol 15:576\u2013583","journal-title":"Curr Opin Biotechnol"},{"key":"5504_CR2","doi-asserted-by":"publisher","first-page":"4198","DOI":"10.1021\/jm100181s","volume":"53","author":"MH Bolli","year":"2010","unstructured":"Bolli MH, Abele S, Binkert C, Bravo R, Buchmann S, Bur D, Gatfield J, Hess P, Kohl C, Mangold C et al (2010) 2-Imino-thiazolidin-4-one derivatives as potent, orally active S1P1 receptor agonists. J Med Chem 53:4198\u20134211","journal-title":"J Med Chem"},{"key":"5504_CR3","doi-asserted-by":"publisher","first-page":"21453","DOI":"10.1074\/jbc.C200176200","volume":"277","author":"V Brinkmann","year":"2002","unstructured":"Brinkmann V, Davis MD, Heise CE, Albert R, Cottens S, Hof R, Bruns C, Prieschl E, Baumruker T, Hiestand P et al (2002) The immune modulator FTY720 targets sphingosine 1-phosphate receptors. J Biol Chem 277:21453\u201321457","journal-title":"J Biol Chem"},{"key":"5504_CR4","first-page":"1871","volume":"119","author":"E Camerer","year":"2009","unstructured":"Camerer E, Regard JB, Cornelissen I, Srinivasan Y, Duong DN, Palmer D, Pham TH, Wong JS, Pappu R, Coughlin SR (2009) Sphingosine-1-phosphate in the plasma compartment regulates basal and inflammation-induced vascular leak in mice. J Clin Invest 119:1871\u20131879","journal-title":"J Clin Invest"},{"key":"5504_CR5","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23052667","volume":"23","author":"Z-Y Chang","year":"2022","unstructured":"Chang Z-Y, Liu H-M, Leu Y-L, Hsu C-H, Lee T-Y (2022) Modulation of gut microbiota combined with upregulation of intestinal tight junction explains anti-inflammatory effect of corylin on colitis-associated cancer in mice. Int J Mol Sci 23:2667","journal-title":"Int J Mol Sci"},{"key":"5504_CR6","doi-asserted-by":"publisher","first-page":"380","DOI":"10.3390\/ijms19020380","volume":"19","author":"CY Chen","year":"2018","unstructured":"Chen CY, Chen CC, Shieh TM, Hsueh C, Wang SH, Leu YL, Lian JH, Wang TH (2018) Corylin suppresses hepatocellular carcinoma progression via the inhibition of epithelial-mesenchymal transition, mediated by long noncoding RNA gas5. Int J Mol Sci 19:380","journal-title":"Int J Mol Sci"},{"key":"5504_CR7","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1056\/NEJMoa1800149","volume":"379","author":"T Chitnis","year":"2018","unstructured":"Chitnis T, Arnold DL, Banwell B, Brueck W, Ghezzi A, Giovannoni G, Greenberg B, Krupp L, Rostasy K, Tardieu M et al (2018) Trial of fingolimod versus interferon \u03b2-1a in pediatric multiple sclerosis. N Engl J Med 379:1017\u20131027","journal-title":"N Engl J Med"},{"key":"5504_CR8","doi-asserted-by":"publisher","DOI":"10.1186\/s13020-022-00684-7","volume":"17","author":"L-R Deng","year":"2022","unstructured":"Deng L-R, Han Q, Zou M, Chen F-J, Huang C-Y, Zhong Y-M, Wu Q-Y, Tomlinson B, Li Y-H (2022) Identification of potential immunomodulators from Pulsatilla decoction that act on therapeutic targets for ulcerative colitis based on pharmacological activity, absorbed ingredients, and in-silico molecular docking. Chin Med 17:132","journal-title":"Chin Med"},{"key":"5504_CR9","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1407347","volume":"15","author":"D Dong","year":"2024","unstructured":"Dong D, Yu X, Tao X, Wang Q, Zhao L (2024) S1P\/S1PR1 signaling is involved in the development of nociceptive pain. Front Pharmacol 15:1407347","journal-title":"Front Pharmacol"},{"key":"5504_CR10","doi-asserted-by":"publisher","first-page":"2316","DOI":"10.3390\/s7102316","volume":"7","author":"Y Fang","year":"2007","unstructured":"Fang Y (2007) Non-invasive optical biosensor for probing cell signaling. Sensors Basel 7:2316\u20132329","journal-title":"Sensors Basel"},{"key":"5504_CR11","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1016\/S2468-1253(20)30188-6","volume":"5","author":"BG Feagan","year":"2020","unstructured":"Feagan BG, Sandborn WJ, Danese S, Wolf DC, Liu WJ, Hua SY, Minton N, Olson A, D\u2019Haens G (2020) Ozanimod induction therapy for patients with moderate to severe Crohn\u2019s disease: a single-arm, phase 2, prospective observer-blinded endpoint study. Lancet Gastroenterol Hepatol 5:819\u2013828","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"5504_CR12","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/bs.mcb.2015.11.004","volume":"132","author":"CA Flanagan","year":"2016","unstructured":"Flanagan CA (2016) GPCR-radioligand binding assays. Methods Cell Biol 132:191\u2013215","journal-title":"Methods Cell Biol"},{"key":"5504_CR13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2025.120153","volume":"352","author":"Z Fu","year":"2025","unstructured":"Fu Z, Zhou H, Liu H, Li X, Cao L, Zheng W (2025) Sanleng Wan inhibits endometriosis progression by regulating sphingolipid metabolism via the S1P\/S1PR1-Akt axis based on serum metabolomics and network pharmacology. J Ethnopharmacol 352:120153","journal-title":"J Ethnopharmacol"},{"key":"5504_CR14","doi-asserted-by":"publisher","first-page":"1884","DOI":"10.1080\/10428194.2021.1894642","volume":"62","author":"Y Gao","year":"2021","unstructured":"Gao Y, Ding X (2021) miR-145-5p exerts anti-tumor effects in diffuse large B-cell lymphoma by regulating S1PR1\/STAT3\/AKT pathway. Leuk Lymphoma 62:1884\u20131891","journal-title":"Leuk Lymphoma"},{"key":"5504_CR15","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1111\/bcp.13203","volume":"83","author":"T Harada","year":"2017","unstructured":"Harada T, Wilbraham D, de La Borderie G, Inoue S, Bush J, Camm AJ (2017) Cardiac effects of amiselimod compared with fingolimod and placebo: results of a randomised, parallel-group, phase I study in healthy subjects. Br J Clin Pharmacol 83:1011\u20131027","journal-title":"Br J Clin Pharmacol"},{"key":"5504_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2021.113872","volume":"270","author":"T Hou","year":"2021","unstructured":"Hou T, Xu F, Peng X, Zhou H, Zhang X, Qiu M, Wang J, Liu Y, Liang X (2021) Label-free cell phenotypic study of opioid receptors and discovery of novel mu opioid ligands from natural products. J Ethnopharmacol 270:113872","journal-title":"J Ethnopharmacol"},{"key":"5504_CR17","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.111814","volume":"131","author":"Y Huang","year":"2024","unstructured":"Huang Y, Chen X, Liu X, Lin C, Wang Y (2024) The coumarin component isofraxidin targets the G-protein-coupled receptor S1PR1 to modulate IL-17 signaling and alleviate ulcerative colitis. Int Immunopharmacol 131:111814","journal-title":"Int Immunopharmacol"},{"key":"5504_CR18","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1016\/S1474-4422(18)30202-3","volume":"17","author":"R Hughes","year":"2018","unstructured":"Hughes R, Dalakas MC, Merkies I, Latov N, L\u00e9ger JM, Nobile-Orazio E, Sobue G, Genge A, Cornblath D, Merschhemke M et al (2018) Oral fingolimod for chronic inflammatory demyelinating polyradiculoneuropathy (FORCIDP Trial): a double-blind, multicentre, randomised controlled trial. Lancet Neurol 17:689\u2013698","journal-title":"Lancet Neurol"},{"key":"5504_CR19","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1007\/s40263-015-0297-0","volume":"30","author":"SF Hunter","year":"2016","unstructured":"Hunter SF, Bowen JD, Reder AT (2016) The direct effects of fingolimod in the central nervous system: implications for relapsing multiple sclerosis. CNS Drugs 30:135\u2013147","journal-title":"CNS Drugs"},{"key":"5504_CR20","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1016\/j.devcel.2012.07.015","volume":"23","author":"B Jung","year":"2012","unstructured":"Jung B, Obinata H, Galvani S, Mendelson K, Ding B-S, Skoura A, Kinzel B, Brinkmann V, Rafii S, Evans T et al (2012) Flow-regulated endothelial S1P receptor-1 signaling sustains vascular development. Dev Cell 23:600\u2013610","journal-title":"Dev Cell"},{"key":"5504_CR21","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2023.115182","volume":"250","author":"OJ Kandjani","year":"2023","unstructured":"Kandjani OJ, Yaqoubi S, Vahdati SS, Borhannejad B, Dastmalchi S, Alizadeh AA (2023) S1PR1 modulators in multiple sclerosis: Efficacy, safety, comparison, and chemical structure insights. Eur J Med Chem 250:115182","journal-title":"Eur J Med Chem"},{"key":"5504_CR22","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1177\/1352458517728343","volume":"24","author":"L Kappos","year":"2018","unstructured":"Kappos L, Arnold DL, Bar-Or A, Camm AJ, Derfuss T, Sprenger T, Davies M, Piotrowska A, Ni P, Harada T (2018) Two-year results from a phase 2 extension study of oral Amiselimod in relapsing multiple sclerosis. Mult Scler 24:1605\u20131616","journal-title":"Mult Scler"},{"key":"5504_CR23","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1001\/jamaneurol.2021.0405","volume":"78","author":"L Kappos","year":"2021","unstructured":"Kappos L, Fox RJ, Burcklen M, Freedman MS, Havrdova EK, Hennessy B, Hohlfeld R, Lublin F, Montalban X, Pozzilli C et al (2021) Ponesimod compared with teriflunomide in patients with relapsing multiple sclerosis in the active-comparator phase 3 Optimum study a randomized clinical trial. JAMA Neurol 78:558\u2013567","journal-title":"JAMA Neurol"},{"key":"5504_CR24","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1007\/978-1-61779-126-0_20","volume":"746","author":"M Kocan","year":"2011","unstructured":"Kocan M, Pfleger KDG (2011) Study of GPCR-protein interactions by BRET. Methods Mol Biol 746:357\u2013371","journal-title":"Methods Mol Biol"},{"key":"5504_CR25","doi-asserted-by":"publisher","first-page":"2076","DOI":"10.1172\/JCI71194","volume":"124","author":"M Kono","year":"2014","unstructured":"Kono M, Tucker AE, Tran J, Bergner JB, Turner EM, Proia RL (2014) Sphingosine-1-phosphate receptor 1 reporter mice reveal receptor activation sites in vivo. J Clin Invest 124:2076\u20132086","journal-title":"J Clin Invest"},{"key":"5504_CR26","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1093\/cvr\/cvaa046","volume":"117","author":"Y Kuang","year":"2021","unstructured":"Kuang Y, Li X, Liu X, Wei L, Chen X, Liu J, Zhuang T, Pi J, Wang Y, Zhu C et al (2021) Vascular endothelial S1pr1 ameliorates adverse cardiac remodelling via stimulating reparative macrophage proliferation after myocardial infarction. Cardiovasc Res 117:585\u2013599","journal-title":"Cardiovasc Res"},{"key":"5504_CR27","doi-asserted-by":"publisher","first-page":"9508","DOI":"10.1021\/acs.jmedchem.7b00785","volume":"60","author":"H Kurata","year":"2017","unstructured":"Kurata H, Kusumi K, Otsuki K, Suzuki R, Kurono M, Komiya T, Hagiya H, Mizuno H, Shioya H, Ono T et al (2017) Discovery of a 1-Methyl-3,4-dihydronaphthalene-based sphingosine-1-phosphate (S1P) receptor agonist ceralifimod (ONO-4641). A S1P1 and S1P5 selective agonist for the treatment of autoimmune diseases. J Med Chem 60:9508\u20139530","journal-title":"J Med Chem"},{"key":"5504_CR28","doi-asserted-by":"publisher","first-page":"859","DOI":"10.3390\/ph18060859","volume":"18","author":"F Lu","year":"2025","unstructured":"Lu F, Wang G, Yang X, Luo J, Ma H, Pan L, Yao Y, Xie K (2025) Sphk1-S1P signaling drives fibrocyte-mediated pulmonary fibrosis: mechanistic insights and therapeutic potential. Pharmaceuticals (Basel) 18:859","journal-title":"Pharmaceuticals (Basel)"},{"key":"5504_CR29","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1007\/978-1-62703-086-1_5","volume":"937","author":"ICB Marshall","year":"2013","unstructured":"Marshall ICB, Owen DE, McNulty S (2013) Measuring Ca+ changes in multiwell format using the fluorometric imaging plate reader (FLIPR). Methods Mol Biol 937:103\u2013109","journal-title":"Methods Mol Biol"},{"key":"5504_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-49893-8","volume":"15","author":"Y Maruyama","year":"2024","unstructured":"Maruyama Y, Ohsawa Y, Suzuki T, Yamauchi Y, Ohno K, Inoue H, Yamamoto A, Hayashi M, Okuhara Y, Muramatsu W et al (2024) Pseudoirreversible inhibition elicits persistent efficacy of a sphingosine 1-phosphate receptor 1 antagonist. Nat Commun 15:5743","journal-title":"Nat Commun"},{"key":"5504_CR31","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/nature02284","volume":"427","author":"M Matloubian","year":"2004","unstructured":"Matloubian M, Lo CG, Cinamon G, Lesneski MJ, Xu Y, Brinkmann V, Allende ML, Proia RL, Cyster JG (2004) Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature 427:355\u2013360","journal-title":"Nature"},{"key":"5504_CR32","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.3641","volume":"10","author":"BT Milliken","year":"2020","unstructured":"Milliken BT, Doyle RP, Holz GG, Chepurny OG (2020) FRET reporter assays for cAMP and calcium in a 96-well format using genetically encoded biosensors expressed in living cells. Bio-Protoc 10:e3641","journal-title":"Bio-Protoc"},{"key":"5504_CR33","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1194\/jlr.M034108","volume":"54","author":"DC Montrose","year":"2013","unstructured":"Montrose DC, Scherl EJ, Bosworth BP, Zhou XK, Jung B, Dannenberg AJ, Hla T (2013) S1P1 localizes to the colonic vasculature in ulcerative colitis and maintains blood vessel integrity. J Lipid Res 54:843\u2013851","journal-title":"J Lipid Res"},{"key":"5504_CR34","doi-asserted-by":"publisher","first-page":"1713","DOI":"10.1158\/0008-5472.CAN-17-1423","volume":"78","author":"M Nagahashi","year":"2018","unstructured":"Nagahashi M, Yamada A, Katsuta E, Aoyagi T, Huang WC, Terracina KP, Hait NC, Allegood JC, Tsuchida J, Yuza K et al (2018) Targeting the SPHK1\/S1P\/S1PR1 axis that links obesity, chronic inflammation, and breast cancer metastasis. Cancer Res 78:1713\u20131725","journal-title":"Cancer Res"},{"key":"5504_CR35","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1021\/acs.jnatprod.9b01285","volume":"83","author":"DJ Newman","year":"2020","unstructured":"Newman DJ, Cragg GM (2020) Natural products as sources of new drugs over the nearly four decades from 01\/1981 to 09\/2019. J Nat Prod 83:770\u2013803","journal-title":"J Nat Prod"},{"key":"5504_CR36","doi-asserted-by":"publisher","first-page":"9082","DOI":"10.1074\/jbc.M610318200","volume":"282","author":"ML Oo","year":"2007","unstructured":"Oo ML, Thangada S, Wu M-T, Liu CH, Macdonald TL, Lynch KR, Lin C-Y, Hla T (2007) Immunosuppressive and anti-angiogenic sphingosine 1-phosphate receptor-1 agonists induce ubipuitinylation and proteasomal degradation of the receptor. J Biol Chem 282:9082\u20139089","journal-title":"J Biol Chem"},{"key":"5504_CR37","doi-asserted-by":"publisher","first-page":"2290","DOI":"10.1172\/JCI45403","volume":"121","author":"ML Oo","year":"2011","unstructured":"Oo ML, Chang S-H, Thangada S, Wu M-T, Rezaul K, Blaho V, Hwang S-I, Han DK, Hla T (2011) Engagement of S1P1-degradative mechanisms leads to vascular leak in mice. J Clin Invest 121:2290\u20132300","journal-title":"J Clin Invest"},{"key":"5504_CR38","doi-asserted-by":"crossref","unstructured":"Otterbach S, Wellman G, Schm\u00f6ckel SM (2021) Saponins of quinoa: structure, function and opportunities. In: Schm\u00f6ckel SM (ed) The Quinoa genome. Springer International Publishing, Cham, pp 119\u2013138","DOI":"10.1007\/978-3-030-65237-1_8"},{"key":"5504_CR39","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1021\/ml300396r","volume":"4","author":"S Pan","year":"2013","unstructured":"Pan S, Gray NS, Gao W, Mi Y, Fan Y, Wang X, Tuntland T, Che J, Lefebvre S, Chen Y et al (2013) Discovery of BAF312 (siponimod), a potent and selective S1P receptor modulator. ACS Med Chem Lett 4:333\u2013337","journal-title":"ACS Med Chem Lett"},{"key":"5504_CR40","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27092818","volume":"27","author":"SJ Park","year":"2022","unstructured":"Park SJ, Kim J, Kim J, Kim Y, Lee EH, Kim HJ, Kim S, Kim B, Kim R, Choi JW et al (2022) Synthesis and evaluation of serinolamide derivatives as sphingosine-1-phosphate-1 (S1P1) receptor agonists. Molecules 27:2818","journal-title":"Molecules"},{"key":"5504_CR41","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16030574","volume":"16","author":"TA Perry","year":"2024","unstructured":"Perry TA, Masand N, Vrzalikova K, Pugh M, Wei W, Hollows R, Bouchalova K, Nohtani M, Fennell E, Bouchal J et al (2024) The oncogenic lipid sphingosine-1-phosphate impedes the phagocytosis of tumor cells by M1 macrophages in diffuse large B cell lymphoma. Cancers (Basel) 16:574","journal-title":"Cancers (Basel)"},{"key":"5504_CR42","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1080\/14656566.2018.1434143","volume":"19","author":"M Pitteri","year":"2018","unstructured":"Pitteri M, Magliozzi R, Bajrami A, Camera V, Calabrese M (2018) Potential neuroprotective effect of fingolimod in multiple sclerosis and its association with clinical variables. Expert Opin Pharmacother 19:387\u2013395","journal-title":"Expert Opin Pharmacother"},{"key":"5504_CR43","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1002\/ehf2.14176","volume":"10","author":"A Polzin","year":"2023","unstructured":"Polzin A, Dannenberg L, Benkhoff M, Barcik M, Keul P, Ayhan A, Weske S, Ahlbrecht S, Trojovsky K, Helten C et al (2023) Sphingosine-1-phosphate improves outcome of no-reflow acute myocardial infarction via sphingosine-1-phosphate receptor 1. ESC Heart Fail 10:334\u2013341","journal-title":"ESC Heart Fail"},{"key":"5504_CR44","doi-asserted-by":"publisher","first-page":"2131","DOI":"10.1089\/neu.2019.6951","volume":"37","author":"Y Qian","year":"2020","unstructured":"Qian Y, Gao C, Zhao X, Song Y, Luo H, An S, Huang J, Zhang J, Jiang R (2020) Fingolimod attenuates lung injury and cardiac dysfunction after traumatic brain injury. J Neurotrauma 37:2131\u20132140","journal-title":"J Neurotrauma"},{"key":"5504_CR45","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1016\/j.chembiol.2012.07.016","volume":"19","author":"J Quancard","year":"2012","unstructured":"Quancard J, Bollbuck B, Janser P, Angst D, Berst F, Buehlmayer P, Streiff M, Beerli C, Brinkmann V, Guerini D et al (2012) A potent and selective S1P1 antagonist with efficacy in experimental autoimmune encephalomyelitis. Chem Biol 19:1142\u20131151","journal-title":"Chem Biol"},{"key":"5504_CR46","first-page":"61","volume":"12","author":"S Ruggieri","year":"2022","unstructured":"Ruggieri S, Quartuccio ME, Prosperini L (2022) Ponesimod in the treatment of relapsing forms of multiple sclerosis: an update on the emerging clinical data. Degener Neurol Neuromuscul Dis 12:61\u201373","journal-title":"Degener Neurol Neuromuscul Dis"},{"key":"5504_CR47","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1093\/ecco-jcc\/jjab012","volume":"15","author":"WJ Sandborn","year":"2021","unstructured":"Sandborn WJ, Feagan BG, Hanauer S, Vermeire S, Ghosh S, Liu WJ, Petersen A, Charles L, Huang V, Usiskin K et al (2021) Long-term efficacy and safety of ozanimod in moderately to severely active ulcerative colitis: results from the open-label extension of the randomized, phase 2 Touchstone study. J Crohns Colitis 15:1120\u20131129","journal-title":"J Crohns Colitis"},{"key":"5504_CR48","doi-asserted-by":"publisher","first-page":"1748","DOI":"10.1038\/nprot.2011.386","volume":"6","author":"R Schroeder","year":"2011","unstructured":"Schroeder R, Schmidt J, Blaettermann S, Peters L, Janssen N, Grundmann M, Seemann W, Kaufel D, Merten N, Drewke C et al (2011) Applying label-free dynamic mass redistribution technology to frame signaling of G protein-coupled receptors noninvasively in living cells. Nat Protoc 6:1748\u20131760","journal-title":"Nat Protoc"},{"key":"5504_CR49","doi-asserted-by":"publisher","first-page":"1778","DOI":"10.1111\/bph.13476","volume":"173","author":"FL Scott","year":"2016","unstructured":"Scott FL, Clemons B, Brooks J, Brahmachary E, Powell R, Dedman H, Desale HG, Timony GA, Martinborough E, Rosen H et al (2016) Ozanimod (RPC1063) is a potent sphingosine-1-phosphate receptor-1 (S1P1) and receptor-5 (S1P5) agonist with autoimmune disease-modifying activity. Br J Pharmacol 173:1778\u20131792","journal-title":"Br J Pharmacol"},{"key":"5504_CR50","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.1155\/2023\/4010797","volume":"2023","author":"M Shen","year":"2023","unstructured":"Shen M, Wang Y-J, Liu Z-H, Chen Y-W, Liang Q-K, Li Y, Ming H-X (2023) Inhibitory effect of Astragalus polysaccharide on premetastatic niche of lung cancer through the S1PR1-STAT3 signaling pathway. Evid Based Complement Alternat Med 2023:1741\u20131427X","journal-title":"Evid Based Complement Alternat Med"},{"key":"5504_CR51","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1038\/nri2974","volume":"11","author":"S Spiegel","year":"2011","unstructured":"Spiegel S, Milstien S (2011) The outs and the ins of sphingosine-1-phosphate in immunity. Nat Rev Immunol 11:403\u2013415","journal-title":"Nat Rev Immunol"},{"key":"5504_CR52","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1007\/s12013-021-01014-8","volume":"79","author":"T Sudhadevi","year":"2021","unstructured":"Sudhadevi T, Jafri A, Ha AW, Basa P, Thomas JM, Fu P, Wary K, Mehta D, Natarajan V, Harijith A (2021) Hyperoxia-induced S1P1 signaling reduced angiogenesis by suppression of TIE-2 leading to experimental bronchopulmonary dysplasia. Cell Biochem Biophys 79:561\u2013573","journal-title":"Cell Biochem Biophys"},{"key":"5504_CR53","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1111\/bph.13641","volume":"174","author":"K Sugahara","year":"2017","unstructured":"Sugahara K, Maeda Y, Shimano K, Mogami A, Kataoka H, Ogawa K, Hikida K, Kumagai H, Asayama M, Yamamoto T et al (2017) Amiselimod, a novel sphingosine 1-phosphate receptor-1 modulator, has potent therapeutic efficacy for autoimmune diseases, with low bradycardia risk. Br J Pharmacol 174:15\u201327","journal-title":"Br J Pharmacol"},{"key":"5504_CR54","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2025.120575","volume":"355","author":"Y Sun","year":"2026","unstructured":"Sun Y, Xu F, Wang J, Liu Y, Hou T, Zhou H, Yuan W, Tang H, Fu D, Liang X (2026) Isobavachalcone ameliorates TNBS-induced Crohn\u2019s disease-like colitis via GPR84-PI3K-AKT axis. J Ethnopharmacol 355:120575","journal-title":"J Ethnopharmacol"},{"key":"5504_CR55","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2024.107387","volume":"147","author":"H Tang","year":"2024","unstructured":"Tang H, Hou T, Zhou H, Liao H, Xu F, Xie X, Yuan W, Guo Z, Liu Y, Wang J et al (2024) Label-free cell phenotypic profiling of histamine H4R receptor and discovery of non-competitive H4R antagonist from natural products. Bioorg Chem 147:107387","journal-title":"Bioorg Chem"},{"key":"5504_CR56","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.molimm.2023.06.006","volume":"160","author":"J Tian","year":"2023","unstructured":"Tian J, Chang S, Wang J, Chen J, Xu H, Huang T, Wang J, Kang J, Fan W, Wang Y (2023) S1P\/S1PR1 axis promotes macrophage M1 polarization through NLRP3 inflammasome activation in Lupus nephritis. Mol Immunol 160:55\u201366","journal-title":"Mol Immunol"},{"key":"5504_CR57","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.154651","volume":"110","author":"Z-J Wang","year":"2023","unstructured":"Wang Z-J, Chen L-H, Xu J, Xu Q-X, Xu W, Yang X-W (2023) Corylin ameliorates chronic ulcerative colitis via regulating the gut-brain axis and promoting 5-hydroxytryptophan production in the colon. Phytomedicine 110:154651","journal-title":"Phytomedicine"},{"key":"5504_CR58","doi-asserted-by":"publisher","first-page":"6971","DOI":"10.2147\/JIR.S477554","volume":"17","author":"S Wang","year":"2024","unstructured":"Wang S, Zhu C, Zhang S, Ma S, Li B, Zhao S, Zhang W, Sun Z (2024) The combination of gastrodin and gallic acid synergistically attenuates angii-induced apoptosis and inflammation via regulation of sphingolipid metabolism. J Inflamm Res 17:6971\u20136988","journal-title":"J Inflamm Res"},{"key":"5504_CR59","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2023.104775","volume":"299","author":"C Weigel","year":"2023","unstructured":"Weigel C, Bellaci J, Spiegel S (2023) Sphingosine-1-phosphate and its receptors in vascular endothelial and lymphatic barrier function. J Biol Chem 299:104775","journal-title":"J Biol Chem"},{"key":"5504_CR60","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.202300387","volume":"356","author":"F Wunsch","year":"2023","unstructured":"Wunsch F, Nguyen TN, Wolber G, Bermudez M (2023) Structural determinants of sphingosine-1-phosphate receptor selectivity. Arch Pharm 356:e2300387","journal-title":"Arch Pharm"},{"key":"5504_CR61","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01409","volume":"10","author":"L Xiao","year":"2019","unstructured":"Xiao L, Zhou Y, Friis T, Beagley K, Xiao Y (2019) S1p-S1Pr1 signaling: the \u201csphinx\u201d in osteoimmunology. Front Immunol 10:1409","journal-title":"Front Immunol"},{"key":"5504_CR62","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1007\/s12672-025-02241-8","volume":"16","author":"X Xiong","year":"2025","unstructured":"Xiong X, Zeng L, Zeng F, Huang Y, Jia L (2025) Bioinformatics exploration of the S1PR1 receptor in various human cancers and its clinical relevance. Discov Oncol 16:449","journal-title":"Discov Oncol"},{"key":"5504_CR63","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1002\/cpdd.98","volume":"3","author":"J Xu","year":"2014","unstructured":"Xu J, Gray F, Henderson A, Hicks K, Yang J, Thompson P, Oliver J (2014) Safety, pharmacokinetics, pharmacodynamics, and bioavailability of GSK2018682, a sphingosine-1-phosphate receptor modulator, in healthy volunteers. Clin Pharmacol Drug Dev 3:170\u2013178","journal-title":"Clin Pharmacol Drug Dev"},{"key":"5504_CR64","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.105173","volume":"163","author":"F Xu","year":"2021","unstructured":"Xu F, Wang P, Zhang X, Hou T, Qu L, Wang C, Wang J, Liu Y, Liang X (2021) Identification and target-pathway deconvolution of FFA4 agonists with anti-diabetic activity from Arnebia euchroma (Royle) Johnst. Pharmacol Res 163:105173","journal-title":"Pharmacol Res"},{"key":"5504_CR65","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1038\/s41589-021-00930-3","volume":"18","author":"Z Xu","year":"2022","unstructured":"Xu Z, Ikuta T, Kawakami K, Kise R, Qian Y, Xia R, Sun M-X, Zhang A, Guo C, Cai X-H et al (2022) Structural basis of sphingosine-1-phosphate receptor 1 activation and biased agonism. Nat Chem Biol 18:281\u2013288","journal-title":"Nat Chem Biol"},{"key":"5504_CR66","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.155390","volume":"128","author":"X Xu","year":"2024","unstructured":"Xu X, Li S, Wang T, Zhen P, Wei Q, Yu F, Tong J (2024) Mitigation of myocardial ischemia\/reperfusion-induced chronic heart failure via Shexiang Baoxin Pill-mediated regulation of the S1PR1 signaling pathway. Phytomedicine 128:155390","journal-title":"Phytomedicine"},{"key":"5504_CR67","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1042\/BCJ20253088","volume":"482","author":"R Yadav","year":"2025","unstructured":"Yadav R, Zaccolo M (2025) GPCR signaling via cAMP nanodomains. Biochem J 482:519\u2013533","journal-title":"Biochem J"},{"key":"5504_CR68","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-025-03907-7","volume":"25","author":"X Yao","year":"2025","unstructured":"Yao X, Tang M, Li L, Zeng Y (2025) Role of S1PR1 in VEGF-exosomes mediated resistance of hepatocellular carcinoma to anti-angiogenesis therapy. Cancer Cell Int 25:264","journal-title":"Cancer Cell Int"},{"key":"5504_CR69","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1177\/108705719900400206","volume":"4","author":"JH Zhang","year":"1999","unstructured":"Zhang JH, Chung TD, Oldenburg KR (1999) A simple statistical parameter for use in evaluation and validation of high throughput screening assays. J Biomol Screen 4:67\u201373","journal-title":"J Biomol Screen"},{"key":"5504_CR70","first-page":"1910","volume":"32","author":"Y Zhao","year":"2017","unstructured":"Zhao Y, Zhang Q, Liu Y, Wang G, Ge S, Liu H (2017) Study on regulation effect of Dendrobium extracts on endogenous metabolites SIP and related gene expression in the prevention of gastric cancer. J Tradit Chin Med 32:1910\u20131914","journal-title":"J Tradit Chin Med"},{"key":"5504_CR71","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-57124-x","volume":"16","author":"H Zheng","year":"2025","unstructured":"Zheng H, Yu J, Gao L, Wang K, Xu Z, Zeng Z, Zheng K, Tang X, Tian X, Zhao Q et al (2025) S1PR1-biased activation drives the resolution of endothelial dysfunction-associated inflammatory diseases by maintaining endothelial integrity. Nat Commun 16:1826","journal-title":"Nat Commun"},{"key":"5504_CR72","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2021.630291","volume":"8","author":"P Zhou","year":"2021","unstructured":"Zhou P, Zhou L, Shi Y, Li Z, Liu L, Zuo L, Zhang J, Liang S, Kang J, Du S et al (2021) Neuroprotective effects of Danshen Chuanxiongqin Injection against ischemic stroke: metabolomic insights by UHPLC-Q-Orbitrap HRMS analysis. Front Mol Biosci 8:630291\u2013630291","journal-title":"Front Mol Biosci"},{"key":"5504_CR73","doi-asserted-by":"publisher","first-page":"1566","DOI":"10.1038\/s42255-024-01070-3","volume":"6","author":"T Zhou","year":"2024","unstructured":"Zhou T, Cheng J, He S, Zhang C, Gao MX, Zhang LJ, Sun JP, Zhu Y, Ai D (2024) The sphingosine-1-phosphate receptor 1 mediates the atheroprotective effect of eicosapentaenoic acid. Nat Metab 6:1566\u20131583","journal-title":"Nat Metab"}],"container-title":["Naunyn-Schmiedeberg's Archives of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-026-05504-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00210-026-05504-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-026-05504-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T14:02:58Z","timestamp":1787666578000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00210-026-05504-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,29]]},"references-count":73,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["5504"],"URL":"https:\/\/doi.org\/10.1007\/s00210-026-05504-5","relation":{},"ISSN":["0028-1298","1432-1912"],"issn-type":[{"value":"0028-1298","type":"print"},{"value":"1432-1912","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,29]]},"assertion":[{"value":"26 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Conflicts of interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}