PF-543 is a potent inhibitor of sphingosine kinase 1 (SK1; IC50 = 2-3.6 nM) that less effectively inhibits SK2 (IC50 = 356 nM).(1) It does not significantly block the activity of other protein and lipid kinases or bind sphingosine-1-phosphate receptors when tested at a concentration of 10 μM.1 PF-543 prevents the phosphorylation of sphingosine in cancer cells and in whole blood (EC50 = 8.4 and 27 nM respectively).1 Through its effects on SK1 PF-543 prevents sickling hemolysis and inflammation in sickling cell disease transgenic mice.(2) Unlike inhibitors that are selective for SK2 PF-543 does not impair DNA synthesis in human pulmonary arterial smooth muscle cells.(3)
