The immunomodulatory drug fingolimod (FTY720, Gilenya^R) was approved for oral treatment of relapsing-remitting multiple sclerosis, due to its impressive efficacy and good tolerability. Pharmacologically, it acts as an unselective agonist of sphingosine 1-phosphate receptors (S1PR) and as a selective functional antagonist of the S1P₁ subtype by induction of receptor downregulation. Since S1P₁ is crucial for the regulation of lymphocyte trafficking, its downregulation causes redistribution of the immune cells to secondary lymphoid tissues, resulting in the depletion from the circulation and hence immunosuppression. Numerous preclinical studies have since been performed with the aim to increase the spectrum of potential indications for fingolimod with emphasis on other autoimmune disorders and diseases associated with inflammation and uncontrolled cell proliferation, including cancer. As an alternative to fingolimod, novel S1PR modulators with a more selective receptor activation profile and improved pharmacokinetic performance and tolerability have also been developed. Preclinical and clinical studies are ongoing to investigate their therapeutic potential. This review discusses the most relevant preclinical and clinical findings from S1PR-targeting and from less-well defined off-target effects reported in the literature, and reveals perspectives for using fingolimod and functionally-related derivatives and new formulations in the management of an increasing number of diseases.

免疫调节药物芬戈莫德（FTY720，Gilenya ^R）由于其令人印象深刻的疗效和良好的耐受性，被批准用于复发缓解型多发性硬化症的口服治疗。在药理学上，它通过诱导受体下调而充当鞘氨醇1-磷酸受体（S1PR）的非选择性激动剂和S1P ₁亚型的选择性功能拮抗剂。自S1P ₁对于调节淋巴细胞的运输至关重要，它的下调引起免疫细胞向次级淋巴组织的重新分布，导致循环耗竭，从而导致免疫抑制。自那以来，已经进行了许多临床前研究，目的是扩大芬戈莫德的潜在适应症范围，重点是其他自身免疫性疾病和与炎症和不受控制的细胞增殖有关的疾病，包括癌症。作为芬戈莫德的替代品，还开发了新型的S1PR调节剂，其具有更强的选择性受体活化特性以及改善的药代动力学性能和耐受性。临床前和临床研究正在进行中，以研究其治疗潜力。