Inhibitors of sphingosine-1-phosphate metabolism (sphingosine kinases and sphingosine-1-phosphate lyase)

Abstract

Sphingolipids (SLs) are essential structural and signaling molecules of eukaryotic cells. Among them, sphingosine 1 phosphate (S1P) is a recognized promoter of cell survival, also involved, inter alia, in inflammation and tumorigenesis processes. The knowledge and modulation of the enzymes implicated in the biosynthesis and degradation of S1P are capital to control the intracellular levels of this lipid and, ultimately, to determine the cell fate. Starting with a general overview of the main metabolic pathways involved in SL metabolism, this review is mainly focused on the description of the most relevant findings concerning the development of modulators of S1P, namely inhibitors of the enzymes regulating S1P synthesis (sphingosine kinases) and degradation (sphingosine 1 phosphate phosphatase and lyase). In addition, a brief overview of the most significant agonists and antagonists at the S1P receptors is also addressed.

Keywords: Enzymes; Inhibitors; Metabolism; Modulators; Sphingolipid.