Phosphorylation by Sphingosine Kinase 2 is Essential for in vivo Potency of FTY720 Analogues

Decisive diastereomers. Sphingosine kinase 2 (SPHK2) phosphorylation rate was found to be the major limiting factor for decreasing peripheral lymphocyte counts of FTY720‐like derivatives in vivo. For a diastereomeric pair of potent S1P1 agonists, lymphopenia was only observed for the epimer showing...

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Veröffentlicht in:	ChemMedChem 2008-07, Vol.3 (7), p.1027-1029
Hauptverfasser:	Högenauer, Klemens, Billich, Andreas, Pally, Charles, Streiff, Markus, Wagner, Trixie, Welzenbach, Karl, Nussbaumer, Peter
Format:	Artikel
Sprache:	eng
Schlagworte:	biologically active compounds Catalysis Fingolimod Hydrochloride FTY720 immunomodulators Immunosuppressive Agents - chemistry Immunosuppressive Agents - pharmacology medicinal chemistry Models, Chemical Phosphorylation Phosphotransferases (Alcohol Group Acceptor) - chemistry Phosphotransferases (Alcohol Group Acceptor) - metabolism Propylene Glycols - chemistry Propylene Glycols - pharmacology Sphingosine - analogs & derivatives Sphingosine - chemistry Sphingosine - pharmacology sphingosine kinase
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Zusammenfassung:	Decisive diastereomers. Sphingosine kinase 2 (SPHK2) phosphorylation rate was found to be the major limiting factor for decreasing peripheral lymphocyte counts of FTY720‐like derivatives in vivo. For a diastereomeric pair of potent S1P1 agonists, lymphopenia was only observed for the epimer showing an efficient SPHK2 phosphorylation rate of the parent amino alcohol.
ISSN:	1860-7179 1860-7187
DOI:	10.1002/cmdc.200800037