Abstract
Fingolimod (FTY720) is a first-in-class, orally active, sphingosine 1-phosphate (S1P)-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 S1P receptor type 1 (S1P(1)), 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-β1a (AVONEX(®)) 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.
MeSH terms
-
Animals
-
Drug Discovery
-
Encephalomyelitis, Autoimmune, Experimental / drug therapy
-
Encephalomyelitis, Autoimmune, Experimental / immunology
-
Fatty Acids, Monounsaturated / chemistry
-
Fingolimod Hydrochloride
-
Humans
-
Immunosuppressive Agents / chemistry
-
Immunosuppressive Agents / pharmacology
-
Immunosuppressive Agents / therapeutic use*
-
Kidney Transplantation
-
Lymphocytes / drug effects
-
Lymphocytes / immunology
-
Multiple Sclerosis / drug therapy*
-
Multiple Sclerosis / immunology
-
Propylene Glycols / chemistry
-
Propylene Glycols / pharmacology
-
Propylene Glycols / therapeutic use*
-
Receptors, Lysosphingolipid / immunology*
-
Sphingosine / analogs & derivatives*
-
Sphingosine / chemistry
-
Sphingosine / pharmacology
-
Sphingosine / therapeutic use
Substances
-
Fatty Acids, Monounsaturated
-
Immunosuppressive Agents
-
Propylene Glycols
-
Receptors, Lysosphingolipid
-
Fingolimod Hydrochloride
-
Sphingosine
-
thermozymocidin