title: Molecular targets of FTY720 (fingolimod).
abstract: FTY720 is a recently approved first line therapy for relapsing forms of multiple sclerosis. In this context, FTY720 is a pro-drug, with its anti-multiple sclerosis, immunosuppressive effects largely elicited following its phosphorylation by sphingosine kinase 2 and subsequent modulation of G protein-coupled sphingosine 1-phosphate (S1P) receptor 1 that induces lymphopenia by altering lymphocyte trafficking. A number of other biological effects of FTY720 have, however, been described, including considerable evidence that this drug also has anti-cancer properties. These other effects of FTY720 are independent of S1P receptors, and appear facilitated by modulation of a range of other recently described protein targets by nonphosphorylated FTY720. Here, we review the direct targets of FTY720 that contribute to its anti-cancer properties. We also discuss other recently described protein effectors that, in combination with S1P receptors, appear to contribute to its immunosuppressive effects.
authors: Centre for Cancer Biology, SA Pathology, Frome Road, Adelaide SA 5000, Australia.
authors: M R
authors: MR
authors: Pitman
authors: J M
authors: JM
authors: Woodcock
authors: A F
authors: AF
authors: Lopez
authors: S M
authors: SM
authors: Pitson
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008231:Lymphopenia / Q000139:chemically induced; D008246:Lysophospholipids / Q000378:metabolism; D009103:Multiple Sclerosis / Q000188:drug therapy*; D009369:Neoplasms / Q000188:drug therapy*; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011409:Propylene Glycols / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology; D049349:Receptors, Lysosphingolipid / Q000378:metabolism; D013110:Sphingosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000099157:Sphingosine Kinase
chemical_list: D000970:Antineoplastic Agents; D000068876:Fingolimod Hydrochloride; D007166:Immunosuppressive Agents; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; D013110:Sphingosine; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate