Sphingosine 1-phosphate chemical biology

A dozen years ago, the term ‘S1P’ (sphingosine 1-phosphate) was not in the lexicons of scientific literature databases. By early 2008, this query term retrieved well over 1000 citations from PubMed — about 225 of these appeared in 2007. Indeed, S1P is arguably the most heavily studied lipid molecule at present. What happened to distinguish S1P among many other signaling lipids? We believe that the seminal event was the linking of the investigational drug, FTY720 (fingolimod), to S1P signaling. This realization profoundly altered understanding of S1P biology, revealing both that S1P is prominent in lymphocyte trafficking and that mimicking S1P signaling with an agonist drug can modulate the immune system to considerable therapeutic benefit. Neither fact was known prior to FTY720; indeed, this molecule is testament to the power of chemical biology. In this communication, we attempt to summarize progress to date in S1P chemical biology.