Other Sphingosine Derivatives and Precursors

N,N-Diacyl sphingosines are potent and specific inhibitors of sphingosine kinase, the key enzyme in the phosphorylation of sphingosine to sphingosine-1-phosphate. They have also been reported to inhibit protein kinase C (an enzyme that is responsible for phosphorylating amino acids) in certain types of cells.1 They induce apoptosis in various cells (including in a number of cancer cell lines), possibly due to the inhibition of sphingosine-1-phosphate synthesis and the resulting increase in ceramides. They also act as a stereospecific enhancer for epidermal growth factor receptor kinase.2

References:

  1. J. Kim et al. “Synthesis and evaluation of sphingoid analogs as inhibitors of sphingosine kinases” Bioorg Med Chem, Vol. 13 pp. 3475-3485, 2005
  2. Y. Igarashi et al. “A Specific Enhancing Effect of N,N-Dimethylsphingosine on Epidermal Growth Factor Receptor Autophosphorylation” Journal of Biological Chemistry, Vol. 265(10) pp. 5385-5389, 1990