Tian Yu-Lin, Jin Jing, Wang Xiao-Jian
Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory ofActive Substance Discovery and Druggability Evaluation, Beijing 100050, China.
Yao Xue Xue Bao. 2012 Jan;47(1):7-17.
Sphingosine-1-phosphate (S1P) is a lysophospholipid signaling molecule that regulates important biological functions in both intracellular and extracellular compartments. It interacts with five G protein-coupled receptors subtypes (S1PR(1-5)) to generate multiple downstream signaling. Activation of S1PR1 has been validated to be involved in the process of immune modulation. Fingolimod (FTY720), the novel S1PR1 agonist, has been approved for the treatment of multiple sclerosis in clinical trials. The study towards discovery of selective S1PR1 agonists has become hot spot for immunological diseases. This article summarized the research progress of S1PR1 agonists, emphasizing their structure types, structure-activity relationship and direction of development.
1-磷酸鞘氨醇（S1P）是一种溶血磷脂信号分子，可调节细胞内和细胞外区室中的重要生物学功能。它与五种G蛋白偶联受体亚型（S1PR(1-5)）相互作用以产生多种下游信号。S1PR1的激活已被证实参与免疫调节过程。新型S1PR1激动剂芬戈莫德（FTY720）已在临床试验中被批准用于治疗多发性硬化症。对选择性S1PR1激动剂的研究已成为免疫疾病领域的热点。本文总结了S1PR1激动剂的研究进展，重点介绍了它们的结构类型、构效关系和发展方向。
