{"title":"鞘氨醇-1-磷酸受体调节剂在多发性硬化症中的临床现状及中枢神经系统不良反应报告。","authors":"Ritika Haldar, Abhijit De","doi":"10.1016/j.drudis.2025.104469","DOIUrl":null,"url":null,"abstract":"<div><div>A novel class of immunomodulatory agents like Sphingosine-1-phosphate receptor (S1PR) modulators has appeared as primarily utilized in the management of relapsing forms of multiple sclerosis (MS) by inhibiting lymphocyte egress from lymph node and reducing peripheral T cell encroachment on the CNS. The first accepted oral S1P modulator, Fingolimod has demonstrated significant efficacy in reducing relapse rates and MRI lesion activity in large-scale clinical trials. Subsequent development of more selective agents, such as siponimod, ozanimod, and ponesimod, has further enhanced therapeutic outcomes by minimizing off-target effects while preserving efficacy. In this review, the role of S1PR modulators in MS management, results from clinical trials, associated CNS adverse effects, and their expanding potential have been discussed and summarized.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 10","pages":"Article 104469"},"PeriodicalIF":7.5000,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Clinical Status and CNS Adverse Drug Report of Sphingosine-1-Phosphate receptor modulators in multiple sclerosis\",\"authors\":\"Ritika Haldar, Abhijit De\",\"doi\":\"10.1016/j.drudis.2025.104469\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>A novel class of immunomodulatory agents like Sphingosine-1-phosphate receptor (S1PR) modulators has appeared as primarily utilized in the management of relapsing forms of multiple sclerosis (MS) by inhibiting lymphocyte egress from lymph node and reducing peripheral T cell encroachment on the CNS. The first accepted oral S1P modulator, Fingolimod has demonstrated significant efficacy in reducing relapse rates and MRI lesion activity in large-scale clinical trials. Subsequent development of more selective agents, such as siponimod, ozanimod, and ponesimod, has further enhanced therapeutic outcomes by minimizing off-target effects while preserving efficacy. In this review, the role of S1PR modulators in MS management, results from clinical trials, associated CNS adverse effects, and their expanding potential have been discussed and summarized.</div></div>\",\"PeriodicalId\":301,\"journal\":{\"name\":\"Drug Discovery Today\",\"volume\":\"30 10\",\"pages\":\"Article 104469\"},\"PeriodicalIF\":7.5000,\"publicationDate\":\"2025-09-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drug Discovery Today\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1359644625001825\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Discovery Today","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1359644625001825","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Clinical Status and CNS Adverse Drug Report of Sphingosine-1-Phosphate receptor modulators in multiple sclerosis
A novel class of immunomodulatory agents like Sphingosine-1-phosphate receptor (S1PR) modulators has appeared as primarily utilized in the management of relapsing forms of multiple sclerosis (MS) by inhibiting lymphocyte egress from lymph node and reducing peripheral T cell encroachment on the CNS. The first accepted oral S1P modulator, Fingolimod has demonstrated significant efficacy in reducing relapse rates and MRI lesion activity in large-scale clinical trials. Subsequent development of more selective agents, such as siponimod, ozanimod, and ponesimod, has further enhanced therapeutic outcomes by minimizing off-target effects while preserving efficacy. In this review, the role of S1PR modulators in MS management, results from clinical trials, associated CNS adverse effects, and their expanding potential have been discussed and summarized.
期刊介绍:
Drug Discovery Today delivers informed and highly current reviews for the discovery community. The magazine addresses not only the rapid scientific developments in drug discovery associated technologies but also the management, commercial and regulatory issues that increasingly play a part in how R&D is planned, structured and executed.
Features include comment by international experts, news and analysis of important developments, reviews of key scientific and strategic issues, overviews of recent progress in specific therapeutic areas and conference reports.