Figure 3.

Fingolimod-relevant chemical structures. Fingolimod and fingolimod-phosphate (fingolimod-P) are structural analogues of sphingosine and sphingosine 1-phosphate (S1P), respectively. S1P is generated via the intracellular ceramide pathway, and ceramide is formed through de novo biosynthesis or degradation of the cell membrane constituent sphingomyelin. Ceramide is N-deacetylated to yield sphingosine, and both sphingosine and fingolimod are phosphorylated by sphingosine kinases to yield S1P and (S)-fingolimod-P, respectively, whereas (R)-fingolimod-P is not found in vivo. The (S)-fingolimod-P is the biologically active principle of the drug in animal models of autoimmune disease (Albert et al., 2005; Brinkmann et al., 2002).