Fingolimod is a first-in-class of sphingosine-1-phosphate (S1P) receptor modulator and is widely used a therapeutic drug for multiple sclerosis (MS), autoimmune disease in the central nervous system. About 25 year ago, a natural product, myriocin was isolated from culture broths of the fungus Isaria sinclairii. Myriocin, a rather complex amino acid having three successive asymmetric centers, was found to show a potent immunosuppressive activity in vitro; however, it induced a strong toxicity in vivo. To find out a less toxic immunosuppressive candidate, the chemical structure of myriocin was simplified to a nonchiral symmetric 2-substituted-2-aminoproane-1,3-diol framework. Finally, a highly potent immunosuppressant, fingolimod was found by the extensive chemical modification and pharmacological evaluation using skin allograft model in vivo. Throughout the analyses of the mechanism action of fingolimod, it is revealed that S1P receptor 1 (S1P₁) plays an essential role in lymphocyte circulation and that the molecular target of fingolimod is S1P₁. Phosphorylated fingolimod acts as a “functional” antagonist at S1P₁, modulates lymphocyte circulation, and shows a potent immunosuppressive activity. Fingolimod significantly reduced the relapse rate of MS in the clinical studies and has been approved as a new therapeutic drug for MS in more than 80 countries.

芬戈莫德是1-磷酸鞘氨醇（S1P）受体调节剂的首创，被广泛用于中枢神经系统多发性硬化症（MS），自身免疫性疾病的治疗药物。大约25年前，从真菌Isaria sinclairii的培养液中分离出了天然产物myriocin。。已发现肉豆蔻酸是具有三个连续不对称中心的相当复杂的氨基酸，在体外显示出有效的免疫抑制活性。然而，它在体内引起强烈的毒性。为了找到毒性较小的免疫抑制候选物，将十四烷柔红霉素的化学结构简化为非手性对称的2-取代的2-氨基丙烷-1,3-二醇骨架。最后，通过体内同种异体移植模型的广泛化学修饰和药理评估，发现了一种高效的免疫抑制剂芬戈莫德。在对芬戈莫德的机制作用的整个分析过程中，发现S1P受体1（S1P ₁）在淋巴细胞循环中起着至关重要的作用，并且芬戈莫德的分子靶标是S1P ₁。磷酸化的芬戈莫德在S1P ₁处充当“功能性”拮抗剂，调节淋巴细胞循环，并显示强效的免疫抑制活性。芬戈莫德在临床研究中显着降低了MS的复发率，并已在80多个国家被批准为MS的新治疗药物。