title: Pharmacology of the sphingosine-1-phosphate signalling system.
abstract: The recent success of FTY720 (Fingolimod, Gilenya(®)), which has been approved for the treatment of relapsing-remitting multiple sclerosis and is the first-in-class sphingosine-1-phosphate (S1P) receptor modulating drug, has boosted the interest in further drug development in this area. Several selective S1P1 receptor-modulating drugs are being investigated in clinical trials for the treatment of diverse autoimmune disorders. Sphingosine kinase inhibitors are under development for the treatment of cancer, aberrant angiogenesis and inflammatory diseases; an inhibitor of SK2 with relatively low affinity is being analysed in patients with advanced solid tumours. While an indirect S1P lyase inhibitor has just failed the proof of concept in patients with rheumatoid arthritis, S1P lyase is still a promising target for the treatment of inflammatory and autoimmune diseases. Another approach is the development of S1P-scavenging or -clearing agents, including a monoclonal S1P antibody that has successfully passed phase I clinical trials and will be further developed for age-related macular degeneration.
authors.affiliation: Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. heringdorf@med.uni-frankfurt.de
authors.forename: Dagmar Meyer
authors.initials: DM
authors.lastname: Zu Heringdorf
authors.forename: Katja
authors.initials: K
authors.lastname: Ihlefeld
authors.forename: Josef
authors.initials: J
authors.lastname: Pfeilschifter
mesh_terms: D000446:Aldehyde-Lyases / Q000037:antagonists & inhibitors; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000068876:Fingolimod Hydrochloride; D006801:Humans; D008246:Lysophospholipids / Q000502:physiology*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors; D011409:Propylene Glycols / Q000627:therapeutic use; D049349:Receptors, Lysosphingolipid / Q000187:drug effects; D015398:Signal Transduction / Q000502:physiology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000502:physiology / Q000627:therapeutic use; D000099157:Sphingosine Kinase
chemical_list: D000446:Aldehyde-Lyases; D004791:Enzyme Inhibitors; D000068876:Fingolimod Hydrochloride; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; D013110:Sphingosine; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate; C022649:sphingosine 1-phosphate lyase (aldolase)