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Fig. 6. AAL(R) is more completely phosphorylated in vivo. Amount of
AAL(R) and AAL-P, or FTY720 and FTY-P, in the blood, 18 h after
intraperitoneal administration of 0.3 mg/kg AAL(R) or FTY720 to
C57BL6 mice (n ϭ 4). Free base (shaded bars) refers to AAL(R) and
FTY720, whereas base phosphate (clear bars) refers to AAL-P and
FTY-P.
much better substrate for SphK2 than FTY720 itself. This
results from a faster enzyme turnover rather than higher
affinity and leads to a significantly more rapid rate of phos-
phorylation in human blood. These results have therapeutic
importance, because the efficacy of FTY720 as an immuno-
suppressant is dependent on the phosphate rather than the
parent compound. First, effective immunosuppression could
be achieved with lower doses of AAL(R) than are needed
with FTY720. Second, use of AAL(R) would reduce the
amount of nonphosphorylated compound in circulation,
thus obviating any effects associated with the nonphosphor-
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