: Sphingosine 1-phosphate (S1P) is extensively researched as a lysophospholipid and is crucial in various physiological and pathological processes. It achieves this via signalling through five different subtypes of G protein-coupled receptors (GPCRs), namely S1PR1 to S1PR5. S1PR modulators possess the ability to traverse the blood-brain barrier, potentially leading to direct ac-tions within the Central Nervous System (CNS). S1PR modulators specifically bind to receptors located on the surface of naive and central memory lymphocytes, causing these cells to be trapped or confined within the lymph node. The investigation of the S1P pathway has resulted in the ap-proval of three S1PR modulators, namely fingolimod, siponimod, and ozanimod, as medications for the treatment of patients suffering from Multiple Sclerosis (MS). Additionally, new S1PR modulators, such as ponesimod and etrasimod, are currently being developed and tested in clini-cal trials. Research on the creation of S1P modulators in neurodegenerative illnesses is ongoing as scientists continue to explore novel possibilities for selective S1P modulators. This study provides a concise overview of sphingolipid metabolism, the mechanism by which S1P receptors are af-fected, and the structural characteristics of several small molecule S1P modulators, with a particu-lar focus on their structure-activity connections.

中文翻译：

---

针对 1-磷酸鞘氨醇受体的小分子调节剂治疗神经退行性疾病的开发现状

：1-磷酸鞘氨醇 (S1P) 作为一种溶血磷脂被广泛研究，在各种生理和病理过程中至关重要。它通过 G 蛋白偶联受体 (GPCR) 的五种不同亚型（即 S1PR1 至 S1PR5）发出信号来实现这一目标。 S1PR 调节剂具有穿越血脑屏障的能力，可能导致中枢神经系统 (CNS) 内的直接作用。 S1PR 调节剂特异性结合位于幼稚淋巴细胞和中央记忆淋巴细胞表面的受体，导致这些细胞被捕获或限制在淋巴结内。对 S1P 通路的研究导致三种 S1PR 调节剂（即芬戈莫德、辛波尼莫德和奥扎尼莫德）被批准作为治疗多发性硬化症 (MS) 患者的药物。此外，新的 S1PR 调节剂，例如 ponesimod 和 etrasimod，目前正在临床试验中开发和测试。随着科学家们不断探索选择性 S1P 调节剂的新可能性，关于在神经退行性疾病中创建 S1P 调节剂的研究正在进行中。本研究简要概述了鞘脂代谢、S1P 受体受影响的机制以及几种小分子 S1P 调节剂的结构特征，特别关注它们的结构-活性联系。