Fingolimod (FTY720, Gilenya) was the first US Food and Drug Administration-approved oral therapy for relapsing forms of multiple sclerosis (MS). Research on modified fungal metabolites converged with basic science studies that had identified lysophospholipid (LP) sphingosine 1-phosphate (S1P) receptors, providing mechanistic insights on fingolimod while validating LP receptors as drug targets. Mechanism of action (MOA) studies identified receptor-mediated processes involving the immune system and the central nervous system (CNS). These dual actions represent a more general theme for S1P and likely other LP receptor modulators. Fingolimod's direct CNS activities likely contribute to its efficacy in MS, with particular relevance to treating progressive disease stages and forms that involve neurodegeneration. The evolving understanding of fingolimod's MOA has provided strategies for developing next-generation compounds with superior attributes, suggesting new ways to target S1P as well as other LP receptor modulators for novel therapeutics in the CNS and other organ systems.

中文翻译：

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芬戈莫德：治疗多发性硬化症和其他疾病的经验教训和新机遇。

Fingolimod（FTY720，Gilenya）是美国食品药品监督管理局批准的首个针对复发型多发性硬化症（MS）的口服疗法。修饰真菌代谢产物的研究与已确定溶血磷脂（LP）鞘氨醇1-磷酸（S1P）受体的基础科学研究相融合，为芬戈莫德提供了机械方面的见解，同时将LP受体作为药物靶标进行了验证。作用机理（MOA）研究确定了受体介导的过程，涉及免疫系统和中枢神经系统（CNS）。这些双重作用代表了S1P和其他可能的LP受体调节剂的更一般主题。芬戈莫德的直接中枢神经系统活动可能有助于其在MS中的功效，特别是与治疗涉及神经退行性疾病的疾病进展阶段和形式特别相关。