Application Notes:
N,N-Dimethylsphingosine is a potent and specific inhibitor of sphingosine kinase, the key enzyme in the phosphorylation of
sphingosine to sphingosine-1-phosphate. It has also been reported to inhibit protein kinase C (another enzyme that is
responsible for phosphorylating amino acids) in certain types of cells.1 It induces apoptosis (including in a number of cancer
cell lines), possibly due to the inhibition of sphingosine-1-phosphate synthesis and the resulting increase in ceramides. It acts
as a stereospecific enhancer for epidermal growth factor receptor kinase.2 At very low doses N,N-dimethylsphingosine
protects the heart against ischemia/reperfusion injury due to its activating sphingosine kinase (via PKCε) which is critical for
myocardial ischemic preconditioning.3 It can help prevent neointimal hyperplasia, which may be the result of inhibiting
ERK-1/2 and Akt signalling, and modulation of smooth muscle growth.4
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
3. Z. Jin and J. Karliner “Low dose N, N-dimethylsphingosine is cardioprotective and activates cytosolic sphingosine kinase by a PKC dependent
mechanism” Journal of Cardiovascular Research, Vol. 71(4)
pp. 725-734, 2006
4. R. McDonald et al. “The sphingosine kinase inhibitor N,N-dimethylsphingosine inhibits neointimal hyperplasia” British Journal of Pharmacology, Vol.
159(3) pp. 543-553, 2010