title: Therapeutic Strategies and Pharmacological Tools Influencing S1P Signaling and Metabolism.
abstract: During the last two decades the study of the sphingolipid anabolic, catabolic, and signaling pathways has attracted enormous interest. Especially the introduction of fingolimod into market as first p.o. therapeutic for the treatment of multiple sclerosis has boosted this effect. Although the complex regulation of sphingosine-1-phosphate (S1P) and other catabolic and anabolic sphingosine-related compounds is not fully understood, the influence on different (patho)physiological states from inflammation to cytotoxicity as well as the availability of versatile pharmacological tools that represent new approaches to study these states are described. Here, we have summarized various aspects concerning the many faces of sphingolipid function modulation by different pharmacological tools up to clinical candidates. Due to the immense heterogeneity of physiological or pharmacological actions and complex cross regulations, it is difficult to predict their role in upcoming therapeutic approaches. Currently, inflammatory, immunological, and/or antitumor aspects are discussed.
authors.affiliation: Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Max-von-Laue-Straße 9, D-60438, Frankfurt, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Vogt
authors.affiliation: Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, Universitätsstraße 1, D-40225, Düsseldorf, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Stark
mesh_terms: D000818:Animals; D015777:Eicosanoids / Q000378:metabolism; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D058990:Molecular Targeted Therapy; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D054852:Small Molecule Libraries / Q000494:pharmacology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000099157:Sphingosine Kinase
chemical_list: D015777:Eicosanoids; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D047428:Protein Kinase Inhibitors; D054852:Small Molecule Libraries; D013110:Sphingosine; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate
keywords: S1P; S1P lyase; S1P receptor; antibodies; ceramide; clinical candidates; fingolimod; sphingosine; sphingosine kinase