Discovery of fingolimod, the sphingosine 1-phosphate receptor modulator and its application for the therapy of multiple sclerosis

Fingolimod (FTY720) is a first-in-class, orally active, sphingosine I-phosphate (SIP)-receptor modulator with a structure closely related to sphingosine. The compound was discovered by chemical modification of a natural product, myriocin. Phosphorylated form of FTY720 acts as a functional antagonist at SIP receptor type I (S inhibits lymphocyte egress from secondary lymphoid organs and shows immunomodulating effects. Phase III studies in multiple sclerosis demonstrated that oral FTY720 had superior efficacy compared with intramuscular IFN-beta 1a (AVONEX (R)) with regard to reducing the rate of relapse and the number of inflammatory lesions in the CNS. FTY720 has been approved as a new therapeutic drug for multiple sclerosis in more than 50 countries, including the USA, Japan and some of those in the EU.