title: Discovery of fingolimod, the sphingosine 1-phosphate receptor modulator and its application for the therapy of multiple sclerosis.
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.
authors.affiliation: Research Division, Mitsubishi Tanabe Pharma Corporation, Yokohama, Kanagawa, 227-0033, Japan. chiba.kenji@ mk.mt-pharma.co.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Chiba
authors.forename: Kunitomo
authors.initials: K
authors.lastname: Adachi
mesh_terms: D000818:Animals; D055808:Drug Discovery; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D011409:Propylene Glycols / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D049349:Receptors, Lysosphingolipid / Q000276:immunology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D005229:Fatty Acids, Monounsaturated; D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine; C001996:thermozymocidin