Therapeutic Strategies and Pharmacological Tools Influencing S1P Signaling and Metabolism
Therapeutic Strategies and Pharmacological Tools Influencing S1P Signaling and Metabolism
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DOI：
10.1002/med.21402
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发表时间：
2017-01
影响因子：
13.3
通讯作者：
D. Vogt;H. Stark
中科院分区：
文献类型：
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作者：
D. Vogt;H. Stark
在过去的二十年中，对鞘脂合成代谢、分解代谢和信号通路的研究引起了人们极大的兴趣。特别是将芬戈莫德作为第一种口服制剂引入市场。用于治疗多发性硬化症的治疗剂增强了这种效果。虽然鞘氨醇-1-磷酸（S1 P）和其他分解代谢和合成代谢鞘氨醇相关化合物的复杂调节尚未完全了解，但对从炎症到细胞毒性的不同（病理）生理状态的影响以及代表研究这些状态的新方法的通用药理学工具的可用性进行了描述。在这里，我们已经总结了不同的药理学工具，以临床候选人的鞘脂功能调节的许多方面。由于生理或药理作用的巨大异质性和复杂的交叉调节，很难预测它们在即将到来的治疗方法中的作用。目前，炎症，免疫和/或抗肿瘤方面进行了讨论。
During the last two decades the study of the sphingolipid anabolic, catabolic, and signaling pathways has attracted enormous interest. Especially the introduction of fingolimod into market as first p.o. therapeutic for the treatment of multiple sclerosis has boosted this effect. Although the complex regulation of sphingosine‐1‐phosphate (S1P) and other catabolic and anabolic sphingosine‐related compounds is not fully understood, the influence on different (patho)physiological states from inflammation to cytotoxicity as well as the availability of versatile pharmacological tools that represent new approaches to study these states are described. Here, we have summarized various aspects concerning the many faces of sphingolipid function modulation by different pharmacological tools up to clinical candidates. Due to the immense heterogeneity of physiological or pharmacological actions and complex cross regulations, it is difficult to predict their role in upcoming therapeutic approaches. Currently, inflammatory, immunological, and/or antitumor aspects are discussed.