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

Abstract

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.