S1P signaling: new therapies and opportunities.
S1P signaling: new therapies and opportunities.
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DOI：
10.12703/p6-109
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Rosen H
中科院分区：
文献类型：
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作者：
Gonzalez-Cabrera PJ;Brown S;Studer SM;Rosen H
开发鞘氨醇-1-磷酸受体1(S1P1)调节剂来抑制炎症及其后遗症在治疗以显著免疫病理学为特征的疾病方面正变得越来越有希望。正如非选择性S1P受体调节剂FTY720(Fingolimod[Gilenya®])在治疗复发-缓解型多发性硬化症(MS)中所显示的那样，使用S1P1调节精确阻断免疫细胞流量的能力-免疫调节-同时保持免疫监控，为其他各种免疫衍生的慢性病理疾病打开了治疗机会，包括炎症性肠病(IBD)、狼疮、牛皮癣，以及潜在的早期急性病毒呼吸道感染。跨S1P受体调节剂对S1P1具有高选择性的验证动物模型的概念验证研究，如BAF-312(Siponimod)，KRP-203，ONO-4641(Ceralifimod)，Ponesimod和RPC-1063，以及新出现的对人类安全和疗效的临床试验，尤其是对多发性硬化症，溃疡性结肠炎(UC)和牛皮癣，为我们考虑对其他各种自身免疫性疾病进行更多测试奠定了基础。
Development of sphingosine-1-phosphate receptor 1 (S1P1) modulators to dampen inflammation and its sequelae is becoming increasingly promising for treating medical conditions characterized by significant immunopathology. As shown by the non-selective S1P receptor modulator FTY720 (fingolimod [Gilenya®]) in the treatment of relapsing-remitting multiple sclerosis (MS), the ability to use S1P1 modulation to precisely block immune cell traffic—immunomodulation—while maintaining immunosurveillance, has opened therapeutic opportunities in various other immune-derived chronic pathologies, including inflammatory bowel disease (IBD), lupus, psoriasis, as well as, potentially, in early acute viral respiratory infection. Proof-of-concept studies across validated animal models with S1P receptor modulators highly selective for S1P1, such as BAF-312 (Siponimod), KRP-203, ONO-4641 (Ceralifimod), ponesimod and RPC-1063, and emerging clinical trials for safety and efficacy in humans, particularly in MS, ulcerative colitis (UC) and psoriasis, have set the stage for us to consider additional testing in various other autoimmune diseases.