The sphingosine kinases (SPHK) phosphorylate sphingosine, producing the important lipid mediator sphingosine-1-phosphate (S1P). The two known kinases, SPHK 1 and SPHK 2, have different developmental and tissue expression patterns, suggesting that they have distinct physiological functions. Notably, SPHK 1 is overexpressed in several forms of cancer and inhibition of SPHK 1 inhibits tumor growth. CAY10621 is a selective inhibitor of SPHK 1, both in vitro (IC50 = 3.3 μM) and in U937 cells overexpressing human SPHK 1 (70% inhibition at 5 μM). It has no inhibitory effect on SPHK 2 either in vitro or in cells. Similarly, CAY10621 does not reduce the activity of protein kinase C (PKC) except at very high concentration (>75 μM).
